Does the prescriptive lifestyle of Seventh-day Adventists provide 'immunity' from the secular effects of changes in BMI?
To examine the effect of Seventh-day Adventist (SDA) membership on 'immunity' to the secular effects of changes in BMI. Three independent, cross-sectional, screening surveys conducted by Sydney Adventist Hospital in 1976, 1986 and 1988 and a survey conducted among residents of Melbourne in 2006. Two hundred and fifty-two SDA and 464 non-SDA in 1976; 166 SDA and 291 non-SDA in 1986; 120 SDA and 300-non SDA in 1988; and 251 SDA and 294 non-SDA in 2006. Height and weight measured by hospital staff in 1976, 1986 and 1988; self-reported by respondents in 2006. The mean BMI of non-SDA men increased between 1986 and 2006 (P < 0.001) but did not change for SDA men or non-SDA women. Despite small increases in SDA women's mean BMI (P = 0.030) between 1988 and 2006, this was no different to that of SDA men and non-SDA women in 2006. The diet and eating patterns of SDA men and women were more 'prudent' than those of non-SDA men and women, including more fruit, vegetables, grains, nuts and legumes, and less alcohol, meat, sweetened drinks and coffee. Many of these factors were found to be predictors of lower BMI. The 'prudent' dietary and lifestyle prescriptions of SDA men appear to have 'immunised' them to the secular effects of changes that occurred among non-SDA men's BMI. The dietary and lifestyle trends of SDA women did not reflect the increase in their BMI observed in 2006.


Effect of cisapride on gastroesophageal reflux in children with chronic bronchopulmonary disease: a double-blind cross-over pH-monitoring study.
Fourteen patients with chronic bronchopulmonary disease and suspected of having gastroesophageal reflux were studied for 16 hr by intraesophageal pH monitoring to investigate the effect of the prokinetic drug cisapride. Cisapride was administered orally in a double-blind cross-over study. The initial dose was 0.3 mg/kg, followed by 0.15 mg/kg every 4 hr for 12 hr. Cisapride was shown to be superior to placebo in reducing gastroesophageal reflux. Both during the total recording period and during the sleep period, cisapride significantly decreased the percentage of time during which the pH was 4 or less (vs placebo; total period, -60%; sleep, -80%) and reduced the number of reflux spells of at least 5 min (-64%; -92%). No adverse effects of cisapride were observed.


Cannabis use, other drug use, and risk of subsequent acute care in primary care patients.
Cannabis and other drug use is associated with adverse health events, but little is known about the association of routine clinical screening for cannabis or other drug use and acute care utilization. This study evaluated whether self-reported frequency of cannabis or other drug use was associated with subsequent acute care. This retrospective cohort study used EHR and claims data from 8 sites in Washington State that implemented annual substance use screening. Eligible adult primary care patients (N = 47,447) completed screens for cannabis (N = 45,647) and/or other drug use, including illegal drug use and prescription medication misuse, (N = 45,255) from 3/3/15-10/1/2016. Separate single-item screens assessed frequency of past-year cannabis and other drug use: never, less than monthly, monthly, weekly, daily/almost daily. An indicator of acute care utilization measured any urgent care, emergency department visits, or hospitalizations ≤19 months after screening. Adjusted Cox proportional hazards models estimated risk of acute care. Patients were predominantly non-Hispanic White. Those reporting cannabis use less than monthly (Hazard Ratio [HR] = 1.12, 95 % CI = 1.03-1.21) or daily (HR = 1.24; 1.10-1.39) had greater risk of acute care during follow-up than those reporting no use. Patients reporting other drug use less than monthly (HR = 1.34; 1.13-1.59), weekly (HR = 2.21; 1.46-3.35), or daily (HR = 2.53; 1.86-3.45) had greater risk of acute care than those reporting no other drug use. Population-based screening for cannabis and other drug use in primary care may have utility for understanding risk of subsequent acute care. It is unclear whether findings will generalize to U.S. states with broader racial/ethnic diversity.


New insights of osmoregulatory system changes in ovarian hyperstimulation syndrome.
This study evaluated the osmoregulatory system changes in 39 patients with severe ovarian hyperstimulation syndrome. Plasma osmolality (Posm) less or more than 280 mOsm/kg body weight were associated with inappropriate antidiuretic hormone secretion syndrome and hypovolemia, respectively.


Does thermal biology differ between two colour pattern morphs of a widespread Australian lizard?
Alternative phenotypes allow individuals to pursue different adaptive pathways in response to the same selective challenge. Colour polymorphic species with geographically varying morph frequencies may reflect multiple adaptations to spatial variables such as temperature and climate. We examined whether thermal biology differed between colour morphs of an Australian lizard, the delicate skink, Lampropholis delicata. The delicate skink has two colour pattern morphs, with frequencies varying across latitude and sex: plain (darker, more common at temperate latitudes, more common in males) or striped (lighter, more common at lower latitudes, more common in females). We tested heating and cooling rate, sprint speed, thermal preference, field body temperature and metabolic rate in both morphs and sexes to determine any link between colour and morph frequency distribution. Plain individuals heated more quickly, but other thermal traits showed little variation among morphs. Lampropholis delicata colour influences rates of heat exchange, but the relationship does not appear to be adaptive, suggesting that behavioural thermoregulation homogenises body temperature in the field. While we find no substantial evidence of thermal differences between the two colour morphs, morph-specific behaviour may buffer against differences in heat exchange. Latitudinal variation in species colour may be driven by selection pressures other than temperature.


Spatiotemporal distribution of δ(13)CCO2 in a shallow cave and its potential use as indicator of anthropic pressure.
This study deals with the spatiotemporal dynamics of CO2 and its isotopic composition (δ(13)CCO2) in the atmosphere of Altamira Cave (northern Spain) over two annual cycles. In general terms, the cavity shows two distinct ventilation modes, acting as a CO2 reservoir from October to May (recharge stage), while actively exchanging gases with the outside atmosphere between July and September (discharge stage). In recharge mode, the in-cave air shows higher and relatively homogeneous CO2 values (3332 ± 521 ppm) with lower δ(13)CCO2 (-23.2 ± 0.4‰). In contrast, during the discharge stage, the CO2 concentrations are lower and relatively more variable (1383 ± 435 ppm) and accompanied by higher δ(13)CCO2 (up to -12‰). This seasonal pattern is controlled by the distinct rates of exchange of air masses with the external atmosphere through the annual cycle, as well as by changes in the production of CO2 in the soil and natural fluctuations in the concentration of dissolved inorganic carbon transported by drip water into the cave. In contrast to the interpretations of previous studies in Altamira Cave, no local air intakes into the deepest cave sections were flagged by our δ(13)C measurements. This finding is also supported by analyses of CO2 and (222)Rn in air, density of airborne particles and air temperature. In addition, preliminary experiments examining the visitor-produced disturbances on δ(13)CCO2 were conducted during the various cave ventilation stages to explore the potential use of this parameter as an indicator of anthropic pressure in caves. Our data show that visits (overall stay of 60-85 min; i.e., 4 people for 20 min) significantly affected δ(13)CCO2 (up to Δδ(13)C ∼ -2‰) in the Polychrome Hall of Altamira Cave under conditions of low natural CO2 (discharge stage), whereas it remained almost unaltered under circumstances of high CO2 concentration (recharge stage). This demonstrates that δ(13)CCO2 is sensitive to perturbations produced by visitors during certain periods.


[Clinical experiences with Holoxan in small cell carcinoma of the bronchus (author's transl)].
Clinical experiences obtained until now in the treatment of 47 patients with small cell carcinoma of the bronchus with Holoxan are reported. Special emphasis is laid to the results of a prospective randomized study; two groups of patients, one of them undergoing Holoxan therapy, the other receiving symptomatic treatment, have been investigated in respect of relationship between tumour remission, quality of life and survival time.


Evaluation of an inductively coupled plasma mass spectrometry method for the analysis of sweat chloride and sodium for use in the diagnosis of cystic fibrosis.
Cystic fibrosis (CF) is an autosomal recessive condition that has an incidence of 1:2500 live births in Northern Europe. Due to the large number of mutations that can result in classical or atypical CF phenotype, the sweat test, which quantifies the amount of chloride and sodium in sweat, is vital in supporting the diagnosis of CF. Patients with CF have raised concentrations of chloride and sodium in their sweat; however, it is the concentration of chloride in sweat which provides the greatest diagnostic sensitivity for CF. An inductively coupled plasma mass spectrometry (ICP-MS) method for the analysis of sweat chloride and sodium was evaluated for the routine measurement of sweat collected using the Wescor Macroduct(®) Sweat Collection System. The precision, linearity and agreement with the all laboratories trimmed means (ALTMs) and 'weighed-in' concentrations of sodium and chloride in samples supplied by the UK NEQAS external quality assessment (EQA) Sweat Testing Scheme were assessed. This ICP-MS method for the quantification of chloride and sodium in sweat samples was shown to be accurate, precise and suitable for the routine analysis of sweat chloride and sodium. The method performs well and is now used in the routine analysis of sweat in this laboratory.


The nonspecificity of some radiological signs in excretory urography.
Two radiological signs have recently been offered as being specific for an infected and obstructed urinary tract and renal infarction, respectively. The authors suggest that these signs suggest certain possibilities but do not indicate a specific diagnosis.


Management of delayed oesophagus perforation and osteomyelitis after cervical spine surgery: review of the literature.
Oesophagus perforation is a possible complication of anterior cervical spine surgery, which generally occurs during the first postoperative days. Delayed perforation is very rare and its management remains controversial. We report the successful management of a delayed oesophagus perforation associated with an osteomyelitis.


The ETS genes on chromosome 21 are distal to the breakpoint of the acute myelogenous leukemia translocation (8;21).
The definition of the genetic linkage map of human chromosomes may be helpful in the analysis of cancer-specific chromosome abnormalities. In the translocation (8;21)(q22;q22), a nonrandom cytogenetic abnormality of acute myelogenous leukemia (AML), we previously observed the transposition of the ETS2 gene located at the 21q22 region from chromosome 21 to chromosome 8. However, no ETS2 rearrangements were detected in the DNA of t(8;21)-positive AML cells. Genetic linkage analysis has allowed us to locate the ETS2 gene relative to other loci and to establish that the breakpoint is at an approximate genetic distance of 17 cM from ETS2. When the information from the linkage map is combined with that from molecular studies, it is apparent that (a) the t(8;21) breakpoint does not affect the ETS2 gene structure or the structure of the other four loci proximal to ETS2: D21S55, D21S57, D21S17, and ERG, and ETS-related gene; and (b) the actual DNA sequence involved in the t(8;21) must reside in a 3-cM genetic region between the D21S58 and the D21S55/D21S57 loci, and remains to be identified.


Monoclonal antibodies against differentiation antigens on human macrophages.
Human macrophages matured in vitro from blood monocytes without additional exogenous activation were used to produce monoclonal antibodies (mAbs). Ten of them were selected for high avidity and the best discrimination between mature macrophages and a panel of other cells including freshly prepared monocytes, B cells, T cells, granulocytes and thrombocytes. Five mAbs (MAX. 1, MAX. 2, MAX. 3, MAX. 11, MAX. 24) were found to detect macrophage differentiation antigens. One mAb (MAX. 26) detects an antigen which is shared by mature macrophages and T cells.


A correlative study of internode proportions and sensitivity to procaine in regenerated frog sciatic nerves.
A comparison of regenerated and normal frog sciatic nerves showed a marked reduction in conduction velocity from 37.5 to 15.2 m/s with little change in the absolute refractory period. Changes in conduction velocity corresponded to a reduced mean axon caliber (4.8 versus 6.6 micron). Regenerated nerves also had markedly foreshortened internodes (mean of 309 versus 1236) micron) and thinner sheaths than controls. The geometric proportions of internode length/fiber caliber (l/d) was reduced to approximately one-third of normal. Regenerated nerves were more easily blocked by exposure to 3 mmol/liter procaine than controls, showing greater increase in the absolute refractory, or decreases, respectively, in the peak of the alpha-wave and the area of the compound action potential; the effect of procaine on conduction velocity was less marked. Exposure of various lengths of nerves in chambers of 1, 3, or 20 mm length revealed greater differences for the shorter chambers. The data indicated that some effects could be attributed to the foreshortening of the regenerated internodes. The main difference between normal and regenerated nerves, however, had to be attributed to changes in the nodal membrane characteristics of the latter.


Complexation of furosemide with fulvic acid extracted from shilajit: a novel approach.
The aim of the present work was to complex furosemide (FSM) with fulvic acid (FA) extracted from shilajit with the hope of having a better understanding of the complexation behavior. The effect of FA on the aqueous solubility, dissolution rate, and permeability of FSM was investigated. Different techniques, such as grinding, freeze drying, solvent evaporation, and so forth, were used for the preparation of the complex. The complexes were prepared in molar ratios of 1:1 and 1:2 FSM:FA and were evaluated for drug inclusion, solubility, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, dissolution study, and permeation study. These methods confirm the formation of an amorphous inclusion complex of FSM with FA.


Treatment of respiratory tract infections with pefloxacin in critically ill patients hospitalized in a surgical intensive care unit.
Respiratory tract infections were treated with pefloxacin in fifteen patients, who were hospitalized in the intensive care unit and required artificial ventilation. The treatment was successful in ten patients. Development of resistance was observed in Staphylococcus aureus (two times) and Pseudomonas aeruginosa (four times). No adverse reactions were seen.


Cerebral cortical laminar necrosis on diffusion-weighted MRI in hypoglycaemic encephalopathy.
Laminar necrosis of the cerebral cortex characterized neuropathologically by delayed selective neuronal necrosis occurs in hypoglycaemic encephalopathy and other brain diseases. A 37-year-old male with insulin-treated Type 1 diabetes mellitus developed hypoglycaemic encephalopathy associated with respiratory failure. Brain diffusion-weighted MRI during the subacute period demonstrated high signals along the cerebral cortex. Brain single-photon emission computed tomography showed diffuse, severe cerebral hypoperfusion. The patient remained comatose and died 1 month later. High signals along the cortical bands on diffusion-weighted MRI suggest cortical laminar necrosis, although a postmortem examination was unavailable. Sustained hypoglycaemic brain injury, possibly associated with respiratory hypoxia, may be the underlying mechanism.


Narrowing of the anterior chamber angle during Valsalva maneuver: a possible mechanism for angle closure.
To evaluate changes at the anterior chamber angle during Valsalva maneuver in eyes suspected to have a primary adult glaucoma. Seventy-six consecutive patients underwent recording of applanation tonometry, measurement of the anterior chamber angle recess, angle opening distance, angle recess area, scleral spur-iris root distance, iris thickness, iridociliary angle, ciliary body thickness, anterior chamber depth, and pupil size on ultrasound biomicroscopy before and during the Valsalva maneuver. The Valsalva maneuver was standardized to a pressure of 40 mmHg for 15 seconds, using a manometer. The mean baseline intraocular pressure changed from 19.5+/-4.1 mmHg to 29.5+/-4.8 mmHg during Valsalva (p<0.0001). The anterior chamber angle recess narrowed from 17.9+/-9.5 to 7.8+/-9.2 degrees (p=0.0001). The angle recess area diminished from 0.15+/-0.14 mm2 to 0.14+/-0.12 mm2 (p=0.03) and the scleral spur to iris distance decreased from 0.19+/-0.2 mm to 0.16+/-0.18 mm (p=0.0001). The iridociliary angle narrowed from 72.6+/-33.5 degrees to 62.5+/-32.8 degrees (p=0.04). There was a significant increase in the thickness of the ciliary body, from 0.99+/-0.19 mm to 1.12+/-0.16 mm (p=0.001) and in iris thickness from 0.47+/-0.07 mm to 0.55+/-0.09 mm (p=0.0001). There was no significant change in the angle opening distance, anterior chamber depth, or pupillary diameter. A significant narrowing of the angle to less than 5 degrees was seen in 37 eyes, with iridocorneal apposition present in 28 eyes. After multivariate regression analysis it was found that the baseline ciliary body thickness and angle recess were significant predictors of narrowing of the angle (R2=96.1%). Significant elevation of the intraocular pressure, narrowing of the anterior chamber angle recess, thickening of the ciliary body, and increase in the iris thickness is seen during the Valsalva maneuver. The Valsalva maneuver may lead to angle closure in eyes anatomically predisposed to primary angle closure glaucoma.


Early screening in patients with head and neck cancer identified high levels of pain and distress.
Pain and distress are recognized as the fifth and sixth vital signs in cancer care, respectively, as debilitating symptoms that are frequently under-recognized. The aim of this study was to document, using touch-screen technology, levels of pain and distress in patients with head and neck cancer before their assessment at a head and neck multidisciplinary referral clinic. A cross-sectional study over a 4-year period (2008 through 2011) was conducted for patients attending a head and neck oncology multidisciplinary team clinic in the Hunter New England referral district of Australia. Predictor variables were cancer stage and site. Cancer sites divided into 8 different regions, with distinction made for cutaneous versus noncutaneous sites. Outcome variables consisted of pain and distress levels. Pain was assessed using a Numerical Rating Scale of 0 to 10, and distress was assessed using the Distress Thermometer and PSYCH-6 scales. In the context of a screening study and for statistically comparing pain with other variables, pain was regarded as any score higher than 0. Clinically significant distress represented a Distress Thermometer score higher than 3 and a PSYCH-6 score of at least 3. Data analysis consisted of descriptive statistics, variance contrasts, and 2-tailed Pearson correlations. Four hundred thirty-six patients were included in the study, with an equal number of cutaneous and noncutaneous cancer sites. Thirty-four percent of patients reported having pain, and 13% had clinically significant distress. Tumor stage did not significantly affect pain or distress scores. There is a high level of pain and distress reported by patients with head and neck cancer before their assessment and management is discussed.


Impact of inclement weather on the characteristics of volatile organic compounds in ambient air at the Hsinchu Science Park in Taiwan.
This study describes continuous monitoring of the volatile organic air pollutants, acetone and toluene, in Hsinchu Science Park (HSP) during an occurrence of inclement weather, i.e., a typhoon. Using a lab-designed sampling system coupled with a continuous automated GC-MS analysis system, a total of 53 polar and nonpolar compounds were identified and quantified. The concentration of polar compounds dropped sharply from 41.4 ppbv before the typhoon to the stage of no detection during the storm, but rose again after the typhoon. The amount of nonpolar compounds remained unaffected during the storm. The polar compounds were more affected by both the rainfall and wind than were the nonpolar compounds. The severity of air pollution strongly correlates with the concentration of acetone released into the atmosphere by a wastewater treatment facility. The system used in this study has been proved reliable while working in inclement weather condition; in addition, the results can probably be applied in the monitoring of the environment during the typhoon season in high-tech research areas.


Fracture incidence in GH-deficient patients on complete hormone replacement including GH.
Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. The objective of this study was to evaluate fracture incidence in patients with confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR, 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI, 0.34-0.86) was recorded in AO GHD men. Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.


[End-stage renal failure following parathyroidectomy for advanced primary hyperparathyroidism].
We report two cases of long-standing, advanced primary hyperparathyroidism with renal failure. After surgery the two patients presented with marked hypocalcemia and deterioration of renal function which required dialysis 2 and 3 months after parathyroidectomy. These two cases lead us to consider that renal function should be studied before and after surgery in patients operated on for primary hyperparathyroidism. In 19 patients operated on for hyperparathyroidism with few symptoms and without renal failure or with very moderate renal failure, blood creatinine and creatinine clearance were measured before (T1) and 1 year (T12) parathyroidectomy. No significant overall changes in the following parameters were observed: blood creatinine T1 71 +/- 19 mumol/L, T12 82 +/- 20 mumol/L, CrCl T1 72 +/- 13 mL/min, CrCl T12 70 +/- 19 mL/min. However, in the patient with greatest deterioration of renal function, CrCl decreased from 45 mL/min at T0 to 33 mL/min at T12. A review of the literature shows that in certain cases, renal insufficiency present before cervicotomy may worsen after surgery even if hypercalcemia is corrected. The mechanism is still unclear. A sharp decrease in parathormonemia and parathyroid hypertensive factor may play a role via intrarenal hemodynamic changes.


Outcomes of patent foramen ovale greater than 3 mm at birth in extremely low birthweight infants.
Foramen ovale (FO) is an obligate fetal shunt that typically resolves after birth, although patency throughout life is not uncommon. The natural history of patent FO (PFO) is known in term infants, but less is known about its course in extremely preterm infants. We describe the echocardiographic changes in FO size from birth to discharge in extremely low birth weight (ELBW) infants in this retrospective study. Cohort was divided based on size of FO at birth. Size of FO at discharge was measured and evaluated relative to postnatal weight gain. Demographics and clinical outcomes were compared between the two groups. Of the 54 ELBW infants, 50 were born with FO less than 3 mm in diameter (small), and 4 were born with FO greater than 3 mm (large). Of small defects, the majority (44/50, 88%) did not increase in size with weight gain, and minority (6/50, 12%) increased in size, and three of these 6 patients, FO grew to be slightly larger than 3 mm. In contrast, all large defects (4 of 4, 100%) nearly doubled in size with postnatal growth. These 4 ELBW infants with enlargement of FO had a flap valve evident on echocardiogram obtained prior to discharge, and subsequently closed on outpatient follow-up echocardiograms, although time to resolution was variable (6 months - 3 years). One infant had presumptive resolution because of the presence of flap valve. No maternal or neonatal demographic characteristics were predictive of FO enlargement, although, demonstrable flap valve on discharge echocardiogram correlated with resolution of FO on outpatient follow-up echocardiogram. Therefore, based on our data, we recommend that ELBW infants born with large FO should have echocardiographic re-evaluation of the atrial septal opening prior to discharge, to specify the presence of a flap valve or lack thereof, which is an important detail that can help a neonatologist determine the need for outpatient cardiac follow-up.


Clinicopathological features of sudden unexpected infectious death: population-based study in children and young adults.
Infectious diseases are one of the major causes of sudden death, but data of sudden unexpected death from infectious diseases (SUDID) are sparse in children and young people. The aim of this study is to analyse their epidemiological, clinical, pathological and microbiological characteristics. Population observational study of all deaths due to infectious diseases in people aged 0-34 years in Biscay between 1991 and 2010. The data of Mortality Register and Forensic Pathology Service were analysed. The SUDID cases in which a forensic autopsy was performed were identified. There were 56 SUDID cases (16% of the all sudden deaths). Myocarditis (n=20) and acute bacterial bronchopneumonia/pneumonia (n=18) were the most frequent causes, followed by meningococcemia (n=5) and viral pneumonia (n=4). A chronic co-morbid condition (mainly drug abuse in young people and moderate low birth weight in infants) was recorded in one-third and prodromal symptoms in two-thirds. Seventeen young people had consumed illegal drugs and/or methadone. In 17 of the 23 autopsies where microbiological analyses were performed, the organism responsible was identified. The incidence of SUDID was 0.6/100000 inhabitants/year, representing 5% of all deaths from infectious diseases. SUDID rate was 1.87 times higher in males than in females. The highest incidence occurred in infants (3.7). SUDID is infrequent, but it represents a significant proportion of all sudden deaths in children and young people. The relationship between methadone and bronchopneumonia is noticeable. This article stresses the importance of microbiological analyses in SUDID. Investigation based on forensic pathology provides useful epidemiologic, clinico-pathological and microbiological information for prevention of infectious diseases.


Complications of bariatric surgery.
The rise in bariatric operations has been exponential because of the greater acceptance for these procedures. Although complication rates are relatively low, they can result in formidable disability. Adverse outcomes also result in medical malpractice claims that are particularly problematic for bariatric surgery practices. For these reasons, surgeons performing these operations must be knowledgeable and must possess the technical skills required for managing complications when they occur. The purpose of this article is to review the major complications that occur following anti-obesity procedures and to provide recommendations regarding their management.


The energy dissipation property in bioinspired staggered composites with the viscoelastic matrix.
Many biological materials, such as bone and nacre, exhibit remarkable combinations of stiffness, strength, toughness, and impact resistance over millions of years of evolution. They provide prototypes for designing high-performance artificial composites. However, the dynamic properties of biological materials under impact loading are still not clear. In this study, we establish a dynamic shear-lag model to explore the dynamic response and the energy dissipation capacity of bioinspired staggered composites with a viscoelastic matrix under impact loading. The time domain solution of the dynamic shear-lag model is derived. Then, the model is verified by comparing it with the results from the finite element method. The results demonstrate that matrix viscosity plays a significant role in dissipating the impact energy and enhances the wave transformation between adjacent tablets. Furthermore, there exists an optimal viscosity coefficient to achieve an excellent balance between the rate and efficiency of energy dissipation. The model and the results can not only reveal the energy dissipation property of biological materials but also provide guidelines for the design and optimization of high-performance composites.


Recognition by cellular and humoral autologous immunity in a human osteosarcoma cell line.
Because of the difficulty of developing pairs of osteosarcoma cell lines and cytotoxic T lymphocytes (CTLs), no osteosarcoma tumor antigens that are useful for antiosteosarcoma immunotherapy have yet been identified. In parallel with continuous attempts to develop such pairs from osteosarcoma, we employed serological identification using a recombinant expression cloning (SEREX) method to identify B cell-defined antigens. Consequently, a human osteosarcoma cell line, OS2000, was established from a primary osteosarcoma of a patient cured of hereditary retinoblastoma. Repetitious in vitro stimulations by OS2000 cells to the autologous peripheral T cells induced cytotoxic activity in the autologous osteosarcoma cells but not in the nontumor cells. The cytotoxicity was inhibited by anti-HLA class I monoclonal antibody. SEREX analysis revealed that autologous humoral immunity reacted to two proteins expressed in OS2000. One was the self HLA-Cw*0102 molecule, and the other was wild-type smooth muscle myosin light chain (SMMLC). However, no antigenicity of these proteins was seen versus the sera of the other patients. In conclusion, our results demonstrated the presence of host cellular and humoral immune responses to autologous osteosarcoma cells. This offered the opportunity to identify osteosarcoma antigens recognized by autologous immunity.


Theoretical and treatment issues of personality disorders in individualistic and collectivistic societies.
The author will attempt to equate so-called personality disorders with what used to be called psychoneurosis. Some suggestions for theoretical and technical modifications to apply psychoanalysis and psychotherapy on selective cases within the current managed care environment have been offered. In order to develop a comprehensive and effective psychotherapy system, a collaboration of psychotherapists both in collectivistic and individualistic societies is highly desirable. Furthermore, the differences of personality disorder and neurosis in both social structure are either minimal or insignificant from a psychotherapeutic point of view.


Expression of the nir and nor genes for denitrification of Pseudomonas aeruginosa requires a novel CRP/FNR-related transcriptional regulator, DNR, in addition to ANR.
A gene, designated dnr, was identified in the vicinity of the structural genes for nitrite reductase (nirS) and nitric oxide reductase (norCB), and the gene for activation of the reductases (nirQ) from Pseudomonas aeruginosa. It encodes a protein of 227 amino acids homologous with the CRP/FNR-family transcriptional regulators. Promoter activities for nirS, nirQ and norCB were considerably reduced in the dnr mutant as well as in the mutant of anr, the other fnr-like regulatory gene from P. aeruginosa. This is the first finding that two CRP/FNR-related regulators are involved in denitrification in one strain.


Geant4 Monte Carlo simulation study of the secondary radiation fields at the laser-driven ion source LION.
At the Center for Advanced Laser Applications (CALA), Garching, Germany, the LION (Laser-driven ION Acceleration) experiment is being commissioned, aiming at the production of laser-driven bunches of protons and light ions with multi-MeV energies and repetition frequency up to 1 Hz. A Geant4 Monte Carlo-based study of the secondary neutron and photon fields expected during LION's different commissioning phases is presented. Goal of this study is the characterization of the secondary radiation environment present inside and outside the LION cave. Three different primary proton spectra, taken from experimental results reported in the literature and representative of three different future stages of the LION's commissioning path are used. Together with protons, also electrons are emitted through laser-target interaction and are also responsible for the production of secondary radiation. For the electron component of the three source terms, a simplified exponential model is used. Moreover, in order to reduce the simulation complexity, a two-components simplified geometrical model of proton and electron sources is proposed. It has been found that the radiation environment inside the experimental cave is either dominated by photons or neutrons depending on the position in the room and the source term used. The higher the intensity of the source, the higher the neutron contribution to the total dose for all scored positions. Maximum neutron and photon ambient dose equivalent values normalized to 109 simulated incident primaries were calculated at the exit of the vacuum chamber, where values of about 85 nSv (109 primaries)-1 and 1.0 μSv (109 primaries)-1 were found.


Zirconium (IV)-3-hydroxy-2-tolyl-4H-chromen-4-one complex-the analytical and DFT studies.
Trace determination of Zr(IV) was carried out by its complexation with a newly synthesized chromone derivative, 3-hydroxy-2-tolyl-4H-chromen-4-one (HToC) for the formation of a 1:4 (M:L) yellow-colored complex from the bicarbonate medium maintained at pH 7.90-8.13. The complex was extractable into the non-aqueous organic solvents showing maximum and stable color intensity in dichloromethane in the wavelength range 414-430 nm. The complex obeyed Beer's law showing linearity of calibration curve in the range 0.0-1.1 µg Zr(IV) ml-1 with an optimum range of determination as 0.44-1.0 ppm Zr(IV) detected from the Ringbom plot. Molar absorptivity, specific absorptivity, and Sandell's sensitivity of thus prepared complex were ascertained, respectively as 4.1971 × 104 l mol-1 cm-1, 0.4601 ml g-1 cm-1, and 0.0022 µg Zr(IV) cm-2 at 420 nm. The linear regression equation being [Formula: see text] (Y = absorbance, X = µg Zr(IV) ml-1) with the correlation coefficient of 0.9977 and detection limit of the procedure as 0.0729 µg ml-1. Theoretical calculations were used to determine and compare structural and bonding properties of the Zr(IV)-HToC complex along with justification of the donor sites provided by ligand for complexation with respect to the metal. The consequences obtained were highly cogent with standard deviation of ± 0.0021 absorbance unit. The procedure was applied to various synthetic (some analogous to cooperate and nickel zirconium) and technical (reverberatory flue dust and water) samples with satisfactory results.


Does Continuous Hospice Care Help Patients Remain at Home?
In the U. S., hospices sometimes provide high-intensity "continuous care" in patients' homes. However, little is known about the way that continuous care is used or what impact continuous care has on patient outcomes. To describe patients who receive continuous care and determine whether continuous care reduces the likelihood that patients will die in an inpatient unit or hospital. Data from 147,137 patients admitted to 11 U.S. hospices between 2008 and 2012 were extracted from the electronic medical records. The hospices are part of a research-focused collaboration. The study used a propensity score-matched cohort design. A total of 99,687 (67.8%) patients were in a private home or nursing home on the day before death, and of these, 10,140 (10.2%) received continuous care on the day before death. A propensity score-matched sample (n = 24,658) included 8524 patients who received continuous care and 16,134 patients who received routine care on the day before death. Using the two matched groups, patients who received continuous care on the day before death were significantly less likely to die in an inpatient hospice setting (350/8524 vs. 2030/16,134; 4.1% vs. 12.6%) (odds ratio [OR] 0.29; 95% CI 0.27-0.34; P < 0.001). When patients were cared for by a spouse, the use of continuous care was associated with a larger decrease in inpatient deaths (OR 0.12; 95% CI 0.09-0.16; P < 0.001) compared with those patients cared for by other family members (OR 0.37; 95% CI 0.32-0.42; P < 0.001). It is possible that unmeasured covariates were not included in the propensity score match. Use of continuous care on the day before death is associated with a significant reduction in the use of inpatient care on the last day of life, particularly when patients are cared for by a spouse.


Erucylphosphocholine, a novel antineoplastic ether lipid, blocks growth and induces apoptosis in brain tumor cell lines in vitro.
A potential benefit of alkylphosphocholines in brain tumor therapy was evaluated. The in vitro effects of the intravenously applicable erucylphosphocholine (ErPC) on proliferation, viability, morphology and cell cycle distribution of a rat glioma, four human astrocytoma/glioblastoma and a human medulloblastoma cell line were analyzed daily after continuous drug-exposure for up to six days. ErPC exerted strong cytostatic and direct cytotoxic effects on all cell lines tested at drug concentrations that are achieved in the rat brain after repeated intravenous injections of nontoxic drug doses. Concentrations of 70 microM (T98G, A172, 85HG66, 86HG39) and 110 microM (C6, D283 Med) led to complete cell death within 48-96 h. Particular characteristics of ErPC action are i) the accumulation of cells with a 4n DNA content corresponding to the G2/M-phase of the cell cycle, ii) the formation of two- and multinucleated cells and iii) the induction of apoptosis.


Interference from short-term memory processing on encoding and reproducing brief durations.
A temporal reproduction task is composed of two temporal estimation phases: encoding of the interval to be reproduced, followed by its reproduction. The effect of short-term memory processing on each of these phases was tested in two experiments. In Exp. 1, a memory set was presented, followed by two successive tones bounding the target interval to be reproduced. During the reproduction of the target interval, a probe was presented, and the subject ended the reproduction by pressing one of two keys, depending on the presence or absence of the probe in the memory set. In Exp. 2, probe recognition was required during the encoding of the interval to be reproduced. Whereas in Exp. 1 reproductions lengthened as a function of memory-set size, in Exp. 2 temporal reproductions decreased with set size. These results support attentional models of time estimation and suggest that short-term memory processing interrupts concurrent accumulation of temporal information.


A novel antiviral inhibits Zika virus infection while increasing intracellular glutathione biosynthesis in distinct cell culture models.
We investigated the effects of a specific free-form amino acids formulation on Zika virus replication in two different cell culture model systems, one representative of humans and the other of Old World primates from whom Zika virus was first isolated. Here we present data demonstrating that the formulation of the specific free-form amino acid (FFAAP), comprising cystine, glycine, and a glutamate source, along with a minute concentration of selenium inhibited Zika virus replication by up to 90% with an ED90 (effective dose at which 90% of a dose of Zika virus was inhibited) of 2.5 mM in human cells and 4 mM Vero cells. The ED90 concentration of precursors was innocuous for uninfected cells, but resulted in reduced Zika virus replication by up to 90% at 2-5 mM concentrations in nonhuman primate cells and at 1-3 mM concentration in human placental cells. Two important observations were forthcoming: 1) Zika virus production was decreased by up to 90% in Vero and JEG-3 cells treated with FFAAP (ED90 4.0 mM, and 2.5 mM, respectively) throughout 48-72 h of post infection (hpi) compared to untreated infected cells and 2) Zika virus requires intracellular glutathione for replication in human placental cells, while showing enhanced replication in Vero cells with no glutathione. Relative increases in intracellular glutathione biosynthesis followed FFAAP treatment but blocking intracellular biosynthesis of glutathione in human cells resulted in virus inhibition in human placental cells. The blockade of biosynthesis actually increased Zika virus replication in Vero cells. These findings identify an efficacious inhibitor, FFAAP, of Zika virus replication in both human and nonhuman primate cells, while providing novel insight into the different roles of intracellular glutathione in Zika virus replication.


Prodrug esters of the indolocarbazole CEP-751 (KT-6587).
Prodrug esters of the indolocarbazole CEP-751 (KT-6587) were prepared with the goal of identifying water soluble, stable but cleavable forms for intravenous dosing. A dipeptide proform Lys-beta-Ala (16, CEP-2563/KT-8391) was identified for advancement to clinical trials.


Improved bioconversion of poplar by synergistic treatments with white-rot fungus Trametes velutina D10149 pretreatment and alkaline fractionation.
Successive treatments with fungus and alkali were proposed to reduce the recalcitrance and improved the enzymatic digestibility of triploid poplar. Biopretreatment with Trametes velutina D10149 for 0, 4, 8, 12 and 16weeks gradually degraded hemicelluloses and lignin, and improved the digestibility of cellulose from 4.0% to 19.5% with the increasing dry mass loss of lignocelluloses from 15.5% to 53.4%. Combining with alkaline fractionation, biopretreatment for 4weeks significantly enhanced the availability of cellulose and achieved a maximum glucose yield (38.8% of the original cellulose) with a dry mass loss of 24.4%. The BET surface area of lignocelluloses increased from 1.7 to 10.6m(2)/g after combination of 8weeks biopretreatment and alkaline fractionation. Moreover, alkaline fractionation removed amorphous and low molecular components, which incurred a higher crystalline index and narrower molecular weight distribution of residual carbohydrates in synergistically treated samples as compared to biopretreated samples.


Molecular variability of the P3-6K1 genomic region among geographically and biologically distinct isolates of Plum pox virus.
To evaluate molecular variability in the 5' region of the Plum pox virus (PPV) genome, a fragment spanning the C-terminal part of P3, the complete 6K1 and start of the CI gene in 12 Slovak and French PPV isolates was amplified in IC-RT-PCR and sequenced. Computer analysis of obtained and previously published sequences showed rather substantial differences among isolates of PPV-M and D subgroups (percentage of nucleotide identity ranged from 85.65 to 87.68%). There was a relatively low percentage of heterogeneity among isolates within the same subgroup. Amino acid multiple sequence alignment showed a total of 14 conserved subgroup-specific amino acid positions among PPV-M and D isolates in the examined region. The geographical origin of the isolates was not correlated with their phylogenetic clustering. No reasonable correlation could be established between amino acid substitutions and host species and/or biological properties of isolates. The present IC-RT-PCR detection method targeting a 5' region of the PPV genome, followed by simple RFLP subgroup determination, could enhance conventional CP-based techniques, especially with peculiar isolates. Using this approach, the Slovak isolate BOR-3 was found to be a natural recombinant between a D and an M PPV-type.


Investigating the effect of non-ideal conditions on the performance of a planar CH3NH3PbI3-based perovskite solar cell through SCAPS-1D simulation.
The difference between the simulation and experimental results of solar cells has always been challenging for researchers. Some simplifying assumptions in the simulation programs are the most common reason for this content. However, in some simulation programs, utilizing some nonidealities, the simulated solar cell can approach real conditions. In the present study, we attempted to simulate the conventional FTO/TiO2/CH3NH3PbI3/Spiro-OMeTAD/Au perovskite solar cell by considering resistance paths, reflection in front contact (FTO), and recombination (radiative and Auger) through SCAPS-1D software. For this, the effect of each of these nonidealities was investigated step by step. The efficiency results of the studied solar cell represented significant differences between the efficiency of the device before and after the application of these conditions that was from 19.26% to 8.40%. This significant decrement is mainly due to the reflection and radiative recombination. Besides, to optimize each of the active layers' essential properties, the effect of mentioned parameters, including thickness and doping density, was investigated in terms of efficiency and recombination plots. The novelty of this research was in employing the non-ideal conditions in the simulation phase and approximating them to the reported experimental works' outcomes. Moreover, utilizing the recombination plots helped a lot in choosing the optimum layer property, e.g., doping density selection. Finally, after optimizing all the properties mentioned above, the efficiency was enhanced by about 4% and reached PCE = 12.83%. The general results represent that despite the significant reduction in the cell performance, the simulated cell is closer to the experimental conditions and offers a better model of a solar cell.


Beneficial Short-Term Effects of Bariatric Surgery on Nutritional Inflammatory Profile and Metabolic Biomarkers.
Bariatric surgery (BS) has several potential metabolic benefits. However, little is known about its impact on changes in the inflammatory potential of diet and its effect on inflammatory and metabolic markers. This study aimed to assess the short-term beneficial effects of BS on dietary inflammatory potential and inflammatory and metabolic markers. Participants (n = 20) were evaluated 3 months before and after BS. Body mass, body mass index, anthropometric measurements, fat mass, fat-free mass, visceral fat, skeletal muscle mass, basal metabolic rate, serum lipids, HOMA-IR, QUICKI and inflammatory markers, including leptin, adiponectin, adiponectin/leptin ratio and plasminogen activator inhibitor-1 (PAI-1), were evaluated. Diet data were collected using a 3-day diet record and the dietary inflammatory index (DII®) and energy-adjusted dietary inflammatory index (E-DIITM) scores were computed. There was a reduction in DII® (2.56 vs 2.13) and E-DIITM (2.18 vs 0.45) indicating an improvement in inflammatory nutritional profile. Moreover, there were increases in the adiponectin/leptin ratio (0.08 vs 0.21) and QUICKI scores (0.31 vs 0.37), and reductions in leptin (36.66 vs 11.41 ng/ml) and HOMA-IR scores (3.93 vs 1.50). There were also improvements in body composition and anthropometric parameters. BS promotes changes in metabolic profile, inflammatory state and food intake and these modifications appeared to be associated with improvements in diet-related inflammation, an increase in the adiponectin/leptin ratio and a reduction in leptin. These results contribute to knowledge on the contribution bariatric surgery can make to the treatment of obesity and the reduction of related comorbidities.


Ultrasound applications in drying of fruits from a sustainable development goals perspective.
This review focuses on the many contributions of ultrasound technologies for fruit drying toward the United Nations Sustainable Development Goals (SDG). Along this review, several aspects attained from the application of ultrasound technologies are correlated with the SDGs. The main ultrasonic technologies applied for fruit drying, such as ultrasonic bath, probe ultrasound, air-borne ultrasound air-drying, and ultrasound-assisted contact air-drying, are presented. An in-depth discussion on ultrasound contributions, its advantages, disadvantages, and limitations are made. The effects of ultrasound on water diffusivity in several fruits are presented by correlating this effect with drying time and cost of energy. Ultrasound-assisted fruit drying, like other food processing technologies, directly impacts Zero Hunger, but ultrasound technologies contribute to much more than delivering long shelf-life food. This technology can be used to produce healthy foods and provide well-being, which will be discussed by correlating the effects of ultrasound-assisted air-drying with the concentration of nutritional compounds. Ultrasound-assisted fruit drying reduces wastewater toxicity and energy consumption and improves productivity, potentially improving workplaces and salaries. A walk through the technology is presented from Zero Hunger to No Poverty.


Metabolic decompensation in methylmalonic aciduria: which biochemical parameters are discriminative?
Recurrent, life-threatening metabolic decompensations often occur in patients with methylmalonic aciduria (MMAuria). Our study evaluated (impending) metabolic decompensations in these patients aiming to identify the most frequent and reliable clinical and biochemical abnormalities that could be helpful for decision-making on when to start an emergency treatment. Seventy-six unscheduled and 179 regular visits of 10 patients with confirmed MMAuria continuously followed by our metabolic centre between 1975 and 2009 were analysed. The most frequent symptom of an impending acute metabolic decompensation was vomiting (90% of episodes), whereas symptoms of intercurrent infectious disease (29%) or other symptoms (such as food refusal and impaired consciousness) were found less often. Thirty-five biochemical parameters were included in the analysis. Among them, pathological changes of acid-base balance reflecting metabolic acidosis with partial respiratory compensation (decreased pH, pCO(2), standard bicarbonate, and base excess) and elevated ammonia were the most reliable biochemical parameters for the identification of a metabolic decompensation and the estimation of its severity. In contrast, analyses of organic acids, acylcarnitines and carnitine status were less discriminative. In conclusion, careful history taking and identification of suspicious symptoms in combination with a small number of rapidly available biochemical parameters are helpful to differentiate compensated metabolic condition and (impending) metabolic crisis and to decide when to start an emergency treatment.


The roots of the splanchnic nerves of the rabbit.
The aim of this study was to skeletonize the roots of the greater splanchnic nerve, lesser splanchnic nerve and lumbar splanchnic nerves as well as to investigate their participation in the structure of the celiac plexus in the rabbit.


[Safety and health protection of professional divers in the context of the European Diver Technology Committee (EDTC): technical training and diver competence, role of the "examining" physician].
It is necessary to standardize some parameters for occupational health and safety of their professional diver: risk assessment of work duty, appropriate training program and sanitary surveillance. European Diver Technology Committee (EDCT) gathers the member State's experience about safety procedures, professionals and sanitay surveillance. EDTC criterions to whom it is possible to refer in Italy waiting specific regulations are reported.


Comparison of the toxicity of two treatment schemes with benznidazole for chronic Chagas disease: a prospective cohort study in two Spanish referral centres.
Chagas disease (CD) treatment is limited to two therapeutic options: benznidazole (generally the first option in Spain) and nifurtimox. Both drugs present high rates of adverse reactions and treatment discontinuation and there is no consensus regarding the most effective administration schedule for benznidazole or how to prevent and manage treatment toxicity. We aim to compare the tolerability and treatment discontinuation rate between two different treatment schemes with benznidazole. This was a prospective observational study of adult patients with CD, enrolled from January 2014 to March 2018 in two referral centres in Madrid (Spain). Participants were treated either with benznidazole 5 mg/kg/day (full dose) over 60 days (benznidazole standard dose scheme (BSD)), or with an escalating dose lasting 5 days up to a maximum of 300 mg/day (benznidazole increasing dose scheme (BID)). 471 patients were analysed: 201 in the BSD group and 270 in the BID group. There were no significant differences regarding age (40.4 (SD 8.7) vs 41 (SD 8.2) years), sex (74.1% (149/201) vs 68.5% (185/270) women), weight (69.4 (SD 12.8) vs 68.9 (SD 11) kg) or nationality (97.5% (196/201) vs 96.7% (261/270) Bolivians) between groups. There were also no differences in adverse reactions rate (55.2% (111/201) vs 55.6% (150/270)), number of adverse reactions per patient, adverse reactions type (except for arthralgias and myalgias which occurred more frequently in the BID group (0% (0/111) BSD vs 8% (12/150) BID; p 0.002)) and degree and time to first adverse reactions. There was significantly more treatment discontinuation (49.8% (100/201) vs 33.0% (89/270); p <0.001) in the BSD group, but not during the first 30 days of treatment (32.3% (65/201) vs 25.6% (69/270); p 0.08). The use of increasing doses of benznidazole for 5 days and a maximum dose of 300 mg, does not significantly improve drug tolerability. However, while the treatment discontinuation rates were similar during the first 30 days of treatment, it may improve the treatment completion rate at 60 days.


Stochastic resonance with differential code in feedforward network with intra-layer random connections.
We examined stochastic resonance with a differential coding scheme using a multilayer feedforward neural network which is composed of intra-layer connections. We show that the network, with random synaptic connections in each layer, encodes an input signal into a spike coherence that represents temporal differences among the inputs. We also demonstrate that both internal and external noise enhance the detection of weak signals. Finally, we discuss how the feedforward network with intra-layer random connections is similar to a membrane in its sensitivity to and amplification of a change in stimulus and suggest that the intensity of internal noise may be tuned in a real brain.


Complete genome sequence of Serratia fonticola DSM 4576 T, a potential plant growth promoting bacterium.
Here, we present the first complete genome sequence of Serratia fonticola DSM 4576(T), a potential plant growth promoting (PGP) bacterium which confers solubilization of inorganic phosphate, indole-3-acetic acid production, hydrogen cyanideproduction, siderophore production and assimilation of ammonia through the glutamate synthase (GS/GOGAT) pathway. This genome sequence is valuable for functional genomics and ecological studies which are related to PGP and biocontrol activities.


Induction of thymidine kinase in enzyme-deficient Chinese hamster cells.
Previous work with Chinese hamster cells suggests that thymidine kinase deficiency and loss of potential for plating in HAT medium may arise by a process of mutation coupled with site-specific repression by bromodeoxyuridine at the tk locus. In this study, tk- Chinese hamster cells were exposed to a series of inductors to determine whether revertants for the putative second stage originate by genetic or epigenetic change. Brief exposure to 5-azacytidine resulted in massive conversion to the HAT+ state, and revertants showed levels of thymidine kinase activity intermediate between those of tk- and wild-type cells. By contrast, incidence of HAT+ cells rose only slightly in populations mutagenized with ethyl methanesulfonate. Large increases in frequency of HAT+ cells were obtained by treatment with n-butyrate and L-ethionine, which affect gene expression in other cell systems but have no known mutagenic potential. Induction of HAT+ revertants seems to be mediated by a stable epigenetic shift, which reverses the gradual extinction of thymidine kinase activity in the parent cells. The data support the view that induction in Chinese hamster cells results from changes in DNA methylation patterns, and suggests studies to define the process in molecular terms.


Development of a real-time RT-PCR assay for detection and quantitation of parainfluenza virus 3.
A TaqMan-based real-time RT-PCR assay was developed to detect and quantify human parainfluenza virus 3 (PIV3). Two sets of primer-probe pairs were designed based on the nucleotide (nt) sequence of the nucleocapsid (N) gene. The primer-probe pairs were derived from the 3' end of the N gene (set 1) and the 5' region of the gene (set 2), respectively. Using real-time RT-PCR, the sensitivity of set 1 was determined to be about 9 copies of PIV3 genome, while the sensitivity of set 2 was about 93 copies of PIV3 genome. Set 1 was chosen for subsequent experiments. This primer-probe pair detected PIV3, but not any of several other respiratory viruses, indicating that the assay is PIV3 specific. For clinical evaluation, the assay was employed to test 80 nasopharyngeal aspirates from children with respiratory symptoms. The results confirmed the presence of PIV3 in 12 specimens previously identified as positive by culture confirmation, and showed all of which contained more than 100 copies of PIV3 genome. In addition, the method also detected PIV3 genomes in specimens found negative by culture confirmation, indicating the value of this RT-PCR assay. These data thus demonstrate the application of the real-time RT-PCR assay for the detection and quantification of PIV3 in clinical specimens.


A Cobalt-Nickel Metal-Alloy Thin-Film Sensor for Hydrogen-Phosphate Ion.
Cobalt-nickel alloy thin-films were prepared by electrodepositing on Au-coated Al2O3 substrate from aqueous solutions of metal-salts, and applied as a potentiometric hydrogen-phosphate ion sensor. A doping of 20 mol% nickel in cobalt contributed to enhancing hydrogen-phosphate ion sensing performances, i.e., the sensing range and response time were drastically improved. The Co80Ni20 thin-film electrode showed good potentiometric response to hydrogen-phosphate ion between 1.0 × 10-5 and 1.0 × 10-3 M with a slope of -59 mV/decade and high anion selectivity. The 90% response time to 1 mM H2PO4- was as short as 15 s at pH 5.0, 30°C. A mixed potential sensing mechanism could be proposed on the basis of the results.


A Transarterial Chemoembolization of Balloon-Occluded Alternate Infusions of Cisplatin and Gelatin Particles for Hepatocellular Carcinoma: A Phase I/II Multicenter Prospective Study of Safety and Efficacy.
To evaluate the safety and efficacy of a newly developed technique of balloon-occluded alternate infusions of cisplatin and gelatin particles in transarterial chemoembolization in hepatocellular carcinoma (HCC) and to evaluate the liver damage following the procedure. Forty-three patients with HCC from 4 medical centers were enrolled in this multicenter prospective study. Of these, 41 patients were observed for 6 months following balloon-occluded alternate infusion transarterial chemoembolization. The primary endpoint was the safety of the procedure, and the secondary endpoint was the objective response rate (ORR) of the HCCs at 2 months following treatment. Three patients experienced adverse events, including 1 patient with facial swelling and skin rash, dissection of the celiac artery, and bland portal vein thrombus. No major adverse events were identified. Two (5.3%) patients regressed from a Child-Pugh classification of A to B. The balloon-occluded alternate infusion transarterial chemoembolization treatment achieved a 22.0% complete response (CR) rate and a 73.2% ORR (95% confidence interval [CI], 57.9%-84.4%). In a retrospective analysis of 23 patients with HCCs above the up-to-7 criteria, the CR rate and ORR of the balloon-occluded alternate infusion transarterial chemoembolization were 21.7% and 82.6% (95% CI, 62.3%-93.6%), respectively. Balloon-occluded alternate infusion transarterial chemoembolization is safe and effective for achieving a high ORR while preserving liver function.


Effects of Cryoprotective Medium Composition, Dilution Ratio, and Freezing Rates on Spotted Halibut (Verasper variegatus) Sperm Cryopreservation.
The spotted halibut is species that has a high potential market value in Korea, but the supply of seed is unstable because of the limited milt production of males. The objective of this research was to explore different aspects, such as CPAs, diluents, dilution ratio, and freezing rates, to develop an optimal sperm cryopreservation. The parameters assessed were movable sperm ratio, sperm activity index, survival rate, and DNA damage. The CPAs tested in this research were propylene glycol, dimethyl sulfoxide (DMSO), methanol, ethylene glycol, and glycerol. Different diluents, including 300 mM sucrose, 300 mM glucose, Stain's solution, and Ringer's solution, were investigated. The previous experiment showed that the optimal CPA for cryopreservation was DMSO with a concentration of 15% with 300 mM as diluent. To determine the effect of the dilution ratio, sperm was diluted to 1:1, 1:2, 1:10, 1:100, and 1:1000 with 300 mM sucrose containing DMSO at a final concentration of 15%. Lastly, the optimal freezing rate of the sperm was evaluated with four different freezing rates (-1, -5, -10, and -20 °C/min). Post-thaw sperm motility was higher with a dilution ratio lower than 1:2, and the freezing rate was less than -5 °C/min. In conclusion, these findings represent the development of a cryopreservation protocol for spotted halibut.


Disclosing the Redox Pathway Behind the Excellent Performance of CuS in Solid-State Batteries.
Copper sulfide has attracted increasing attention as conversion-type cathode material for, especially, solid-state lithium-based batteries. However, the reaction mechanism behind its extraordinary electroactivity is not well understood, and the various explanations given by the scientific community are diverging. Herein, the CuS reaction dynamics are highlighted by examining the occurring redox processes via a cutting-edge methodology combining X-ray absorption fine structure spectroscopy, and chemometrics to overcome X-ray diffraction limitations posed by the poor material's crystallinity. The mathematical approach rules out the formation of intermediates and clarifies the direct conversion of CuS to Cu in a two-electron process during discharge and reversible oxidation upon delithiation. Two distinct voltage regions are identified corresponding to Cu- as well as the S-redox mechanisms occurring in the material.


The transcriptional repressor NIPP1 is an essential player in EZH2-mediated gene silencing.
EZH2 is a Polycomb group (PcG) protein that promotes the late-stage development of cancer by silencing a specific set of genes, at least in part through trimethylation of associated histone H3 on Lys 27 (H3K27). Nuclear inhibitor of protein phosphatase-1 (NIPP1) is a ubiquitously expressed transcriptional repressor that has binding sites for the EZH2 interactor EED. Here, we examine the contribution of NIPP1 to EZH2-mediated gene silencing. Studies on NIPP1-deficient cells disclose a widespread and essential role of NIPP1 in the trimethylation of H3K27 by EZH2, not only in the onset of this trimethylation during embryonic development, but also in the maintenance of this repressive mark in proliferating cells. Consistent with this notion, EZH2 and NIPP1 silence a common set of genes, as revealed by gene-expression profiling, and NIPP1 is associated with established Polycomb target genes and with genomic regions that are enriched in Polycomb targets. Furthermore, most NIPP1 target genes are trimethylated on H3K27 and the knockdown of either NIPP1 or EZH2 is often associated with a loss of this modification. Our data reveal that NIPP1 is required for the global trimethylation of H3K27 and is implicated in gene silencing by EZH2.


Determination of selectivity differences for basic compounds in gradient reverse phase high performance liquid chromatography under high pH conditions by partial least squares modelling.
The retention behaviour of compounds in a chromatographic system is believed to be multivariate by nature, i.e. many physico-chemical properties of an analyte can influence its retention. Principal component analysis (PCA) and partial least squares (PLS) can therefore be particularly useful tools for visualising, exploring and modelling the complex interactions between solutes and the mobile and stationary phase. PCA allows the relationships between compounds (the observations) and their retention parameters (the variables) to be visualised in usually just two or three dimensions. PLS can be used to model quantitative structure-retention relationships (QSRRs) and may lead to better understanding of retention and selectivity changes in chromatographic systems. The objective of the study was to investigate the chromatographic behaviour of basic compounds under optimised gradient conditions using octadecyl high performance liquid chromatography (HPLC) columns designed for high pH separations. Three pharmaceutical mixtures were analysed by linear gradient reverse phase HPLC (RP-HPLC) at high pH using ammonia as a pH modifier, and methanol and/or acetonitrile as the organic modifier. The separations were carried out on three octadecyl columns: Waters XTerra MS C18, Agilent Zorbax Extend C18 and Thermo Hypersil-Keystone BetaBasic-18. Multivariate PCA and PLS modelling were employed to explore and explain the differences in selectivity between the chromatographic systems studied when the basic compounds were analysed under the high pH conditions. The interactions between the analytes and the mobile-stationary phases were described by relating the compound molecular descriptors with the selectivity of each chromatographic system. The selectivity differences between the chromatographic systems were identified.


Claudin-1 upregulation is associated with favorable tumor features and a reduced risk for biochemical recurrence in ERG-positive prostate cancer.
Claudin-1 is a membrane-tight junction protein and important for the sealing of the paracellular cleft in epithelial and endothelial cells. Differential expression of Claudin-1 is linked to disease outcome in various cancers. To evaluate the potential relevance of Claudin-1 expression in prostate cancer, a tissue microarray containing samples of 17,747 tumors with annotated clinico-pathological and molecular data was immunohistochemically analyzed for Claudin-1 expression. In normal prostate, glandular cells were always Claudin-1-negative while there was a strong staining of gland-surrounding basal cells. In contrast to normal prostatic glands, a positive Claudin-1 immunostaining, was found, however, in 38.7% of 12,441 interpretable cancers and was considered weak in 12.7%, moderate in 13.2%, and strong in 12.8% of cases. Positive Claudin-1 immunostaining was associated with favorable tumor features like low pT (p = 0.0032), low Gleason grade (p< 0.0001), and a reduced risk of PSA recurrence (p = 0.0005). A positive Claudin-1 staining was markedly more frequent in ERG-positive (63%) than in ERG-negative cancers (23%; p < 0.0001). Subset analyses revealed that all associations of Claudin-1 expression and favorable phenotype and prognosis were driven by ERG-positive cancers. Multivariate analyses revealed, however, that even in ERG-positive cancers, the prognostic impact of high Claudin-1 expression was not independent of established clinico-pathological parameters. Comparison with 12 previously analyzed chromosomal deletions identified conspicuous associations with PTEN and 12p13 deletions potentially indicating functional interactions. These data identify a peculiar role for Claudin-1 in prostate cancer. The protein is overexpressed in a fraction of prostate cancers and increased Claudin-1 expression levels predict a favorable prognosis in ERG-positive cancer.


Hyperviscosity syndrome in rheumatoid arthritis with Felty's syndrome: case report and review of the literature.
Hyperviscosity syndrome (HVS) is characterised by high serum viscosity and the involvement of multiple organs, commonly causing retinal haemorrhage, bleeding diathesis, pulmonary hypertension, congestive heart failure (CHF), neurologic deficits and death. It has been reported that HVS is mostly encountered in Waldenström's macroglobulinaemia (80%-90% of all HVS cases) and occasionally in multiple myeloma. HVS in patients with connective tissue diseases (CTD) has rarely been reported. Of 28 cases of HVS reported in patients with CTD, 19 were with seropositive rheumatoid arthritis (RA). However, only six of these 19 cases had Felty's syndrome. Here we report another case of HVS in a patient with RA as well as Felty's syndrome.


Limitations of craniocaudal thallium-201 and technetium-99m-sestamibi mammoscintigraphy.
Previous studies with 201Tl and 99mTc-sestamibi (MIBI) have used large field of view (LFOV) cameras not optimized for breast imaging. The purpose of this study was to compare these agents and to determine if a small field of view (SFOV) camera designed to minimize the camera-to-breast distance could improve tumor detection. A 28-cm (SFOV) camera was fitted with slant-hole and diverging collimators to perform craniocaudal scintigraphy for direct comparison with mammography. Of the 46 patients studied, 20 had 201Tl imaging alone and 26 had combined 201Tl and MIBI imaging. LFOV (40 cm) breast and axillary images also were obtained. Visual and quantitative analyses of tumor uptake were performed. The SFOV camera with nonparallel collimation showed variable 201Tl and MIBI normal breast activity. This was partly due to significant scatter from cardiac and abdominal activity. Overall, 201Tl had a sensitivity of 53%, which was 67% for tumors > or = 1.5 cm and 20% for tumors < or = 1.5 cm. MIBI sensitivity was 90% (9/10) for lesions > or = 1.5 cm. Specificity was 93% for 201Tl and 83% for MIBI. There was no significant difference in 201Tl (1.76 +/- 0.55) and MIBI (1.82 +/- 0.95) tumor uptake ratios (p = 0.75). Technetium-99m-MIBI was more sensitive than 201Tl for imaging lesions > or = 1.5 cm. Craniocaudal positioning minimized the camera-to-breast distance but did not increase 201Tl detection of tumors < 1.5 cm and increased background breast activity due to scatter.


Plasmacytoid dendritic cell activation is dependent on coordinated expression of distinct amino acid transporters.
Human plasmacytoid dendritic cells (pDCs) are interleukin-3 (IL-3)-dependent cells implicated in autoimmunity, but the role of IL-3 in pDC biology is poorly understood. We found that IL-3-induced Janus kinase 2-dependent expression of SLC7A5 and SLC3A2, which comprise the large neutral amino acid transporter, was required for mammalian target of rapamycin complex 1 (mTORC1) nutrient sensor activation in response to toll-like receptor agonists. mTORC1 facilitated increased anabolic activity resulting in type I interferon, tumor necrosis factor, and chemokine production and the expression of the cystine transporter SLC7A11. Loss of function of these amino acid transporters synergistically blocked cytokine production by pDCs. Comparison of in vitro-activated pDCs with those from lupus nephritis lesions identified not only SLC7A5, SLC3A2, and SLC7A11 but also ectonucleotide pyrophosphatase-phosphodiesterase 2 (ENPP2) as components of a shared transcriptional signature, and ENPP2 inhibition also blocked cytokine production. Our data identify additional therapeutic targets for autoimmune diseases in which pDCs are implicated.


Cardioplegia and slow calcium-channel blockers. Studies with verapamil.
The ability of dl-verapamil to enhance myocardial protection when given before, during, or after myocardial ischemia was assessed with the use of an isolated working rat heart model of cardiopulmonary bypass and ischemic cardiac arrest. Under conditions of normothermic ischemic arrest (30 minutes at 37 degrees C), the addition of verapamil enhanced the protective properties of the St. Thomas' Hospital cardioplegic solution. Optimal protection was observed with verapamil concentrations of 0.5 mg/L (1.09 mumol/L) of cardioplegic solution. Under these conditions, postischemic enzyme leakage was reduced by 32.2% and the postischemic recovery of aortic flow was improved by 18.7%. Despite the additional protection at normothermia, the drug at several concentrations appeared unable to improve functional recovery after an extended period of hypothermic arrest (150 minutes at 20 degrees C), although under these conditions its inclusion in the cardioplegic solution could substantially reduce enzyme leakage. In other studies, the ability of various doses of verapamil alone as a substitute for the cardioplegic solution was examined. At the optimal dose (again 0.5 mg/L), and under normothermic conditions, verapamil alone was a good protection against ischemic injury, although this protection did not match that afforded by the St. Thomas' Hospital cardioplegic solution. In similar studies under hypothermic conditions, the drug failed to afford tissue protection, perhaps indicating some common modality between hypothermia and verapamil-induced protection. Pretreatment with verapamil (0.1 mg/L) prior to ischemia offered moderate additional protection, but its use during reperfusion failed to enhance overall recovery.


An in situ electrosynthesized amperometric biosensor based on lactate oxidase immobilized in a poly-o-phenylenediamine film: determination of lactate in serum by flow injection analysis.
The electrochemical immobilization of lactate oxidase in a poly-o-phenylenediamine film permits the one-step and all-chemical construction of a lactate amperometric biosensor. The sensor was prepared in situ i.e. in the flow injection analysis (FIA) system by simply injecting a plug of a solution containing the monomer and the enzyme. At a flow rate of 50 microL/min linearity was observed up to 0.2 mM lactate and detection limits of about 2 microM could be easily achieved. Faradaic interferences caused by ascorbate, urate, cysteine and acetaminophen were sufficiently minimized to permit lactate determination in diluted serum by FIA. Results obtained by FIA-amperometric detection compared well (according to a proper t-test at a 95% confidence level) with those obtained by a standard enzymatic colorimetric assay. At a flow rate of 1 ml/min a sample throughput higher than 70 sample h-1 was achieved. After one week of continuous use in the FIA system a 75% decrease in biosensor sensitivity was observed.


Association of Serum Ferritin Level in Early Second Trimester of Pregnancy with Development of Gestational Diabetes Mellitus: A Prospective Observational Study.
Gestational diabetes mellitus (GDM) is associated with various maternal and perinatal morbidities. Serum ferritin is a major storage protein of iron and also acts as acute phase reactant which is increased in inflammatory conditions. GDM is a state of insulin resistance and associated with inflammation. The aim of this study was to find the correlation between serum ferritin and development of GDM. To determine the serum ferritin concentration in nonanemic pregnant women and its correlation with subsequent development of GDM. In this prospective observational study, 302 nonanemic pregnant women with singleton gestation between 14 and 20 weeks, attending antenatal OPD, were enrolled. Serum ferritin was measured at the time of enrolment, and they were followed till 24-28 weeks of gestation and subjected to blood glucose test by DIPSI method. A total of 92 women had blood glucose level ≥ 140 mg/dl and were labeled as GDM, and 210 pregnant women with blood glucose level < 140 mg/dl were labeled as non-GDM. Mean serum ferritin level of women with GDM (56.44 ± 19.19 ng/ml) was found to be higher as compared to non-GDM (27.62 ± 12.11 ng/ml), and this difference was found to be statistically significant (p < 0.001). The cutoff value of serum ferritin > 37.55 ng/ml was found to be 85.9% sensitive and 81.9% specific. We can infer that serum ferritin is associated with development of GDM. Based on the findings of the current study, serum ferritin level can be used a predictive marker for the development of GDM.


MCT4-dependent lactate secretion suppresses antitumor immunity in LKB1-deficient lung adenocarcinoma.
Inactivating STK11/LKB1 mutations are genomic drivers of primary resistance to immunotherapy in KRAS-mutated lung adenocarcinoma (LUAD), although the underlying mechanisms remain unelucidated. We find that LKB1 loss results in enhanced lactate production and secretion via the MCT4 transporter. Single-cell RNA profiling of murine models indicates that LKB1-deficient tumors have increased M2 macrophage polarization and hypofunctional T cells, effects that could be recapitulated by the addition of exogenous lactate and abrogated by MCT4 knockdown or therapeutic blockade of the lactate receptor GPR81 expressed on immune cells. Furthermore, MCT4 knockout reverses the resistance to PD-1 blockade induced by LKB1 loss in syngeneic murine models. Finally, tumors from STK11/LKB1 mutant LUAD patients demonstrate a similar phenotype of enhanced M2-macrophages polarization and hypofunctional T cells. These data provide evidence that lactate suppresses antitumor immunity and therapeutic targeting of this pathway is a promising strategy to reversing immunotherapy resistance in STK11/LKB1 mutant LUAD.


Efficacy and safety of acetaminophen and caffeine for the management of acute dental pain: A systematic review.
Because the use of non-steroidal anti-inflammatory drugs and opioids has several restrictions, this review evaluates the efficacy and safety of acetaminophen and caffeine for the management of dental pain. A search of the literature was carried out looking for randomized controlled trials on the use of acetaminophen and caffeine for the management of dental pain, performed on humans and written in English, Italian, French or Arabic languages. The following databases were searched: PubMed, The Cochrane Central Register of Controlled Trials (CENTRAL), Ovid Medline and Scopus. Three controlled clinical trials were retrieved and evaluated by using the Study Quality Assessment Tool of the National Institute for Health and Clinical Excellence. The use of acetaminophen and caffeine appears to be effective in achieving good control of acute dental pain compared to placebo and other analgesic medications, but clinical recommendations cannot be made for the limited number of studies assessed.


Patient and Device Selection for Hemodynamic Support in High-Risk Percutaneous Coronary Intervention.
Coronary artery disease continues to advance resulting in the development of high-risk percutaneous interventions. This includes treatment of patients with multivessel disease, unprotected left main, acute myocardial infarction complicated by cardiogenic shock, and depressed left ventricular ejection fraction. As a result, mechanical circulatory support devices have evolved but require an understanding of patient hemodynamics, device mechanics, and access management. Trial data regarding device selection are limited by inclusion of cardiogenic shock patients, and observational studies are conflicted by selection bias, site familiarity with devices, and complication management; therefore, clinical judgment is required to treat high-risk patients appropriately.


In systemic lupus erythematosus anti-dsDNA antibodies can promote thrombosis through direct platelet activation.
Systemic lupus erythematosus (SLE) is associated with a high risk of venous and arterial thrombosis, not necessarily associated with prothrombotic antiphospholipid antibodies (Abs). Alternatively, thrombosis may be due to an increased titer of anti-dsDNA Abs that presumably promote thrombosis via direct platelet activation. Here, we investigated effects of purified anti-dsDNA Abs from the blood of SLE patients, alone or in a complex with dsDNA, on isolated normal human platelets. We showed that anti-dsDNA Abs and anti-dsDNA Ab/dsDNA complexes induced strong platelet activation assessed by enhanced P-selectin expression and dramatic morphological and ultrastructural changes. Electron microscopy revealed a significantly higher percentage of platelets that lost their discoid shape, formed multiple filopodia and had a shrunken body when treated with anti-dsDNA Abs or anti-dsDNA Ab/dsDNA complexes compared with control samples. In addition, these platelets activated with anti-dsDNA Ab/dsDNA complexes typically contained a reduced number of secretory α-granules that grouped in the middle and often merged into a solid electron dense area. Many activated platelets released plasma membrane-derived microvesicles and/or fell apart into subcellular cytoplasmic fragments. Confocal microscopy revealed that platelets treated with anti-dsDNA Ab/dsDNA complex had a heterogeneous distribution of septin2 compared with the homogeneous distribution in control platelets. Structural perturbations were concomitant with mitochondrial depolarization and a decreased content of platelet ATP, indicating energetic exhaustion. Most of the biochemical and morphological changes in platelets induced by anti-dsDNA Abs and anti-dsDNA Ab/dsDNA complexes were prevented by pre-treatment with a monoclonal mAb against FcγRIIA. The aggregate of data indicates that anti-dsDNA Abs alone or in a complex with dsDNA strongly affect platelets via the FcγRIIA receptor. The immune activation of platelets with antinuclear Abs may comprise a prothrombotic mechanism underlying a high risk of thrombotic complications in patients with SLE.


Explaining the stress-inducing effects of nicotine to cigarette smokers.
To explain how nicotine dependency causes mood fluctuation and increases daily stress. Prospective studies show that taking-up smoking leads to higher stress and depression. Cross-sectional studies show that adult smokers report more irritability, stress and depression than non-smokers. Prospective studies show that smoking cessation leads to enduring mood gains. The adverse mood effects of nicotine dependency are explained by the deprivation reversal model. In between cigarettes, most smokers experience subtle abstinence symptoms, and cumulatively these can increase everyday stress. Hence, adolescents who take up smoking become more stressed, and quitting reduces stress. An explanatory leaflet to explain this model was empirically assessed with tobacco smokers. In a cohort study of 82 cigarette smokers, knowledge levels were significantly enhanced by the explanatory leaflet, and this understanding was maintained 1 week later. Hence, normal cigarette smokers can understand the adverse mood consequences of nicotine addiction. The information leaflet could prove useful for tobacco-education packages in schools, and smoking-cessation packages with adults. The deprivation reversal model can be easily described using a simple leaflet. It explains how nicotine dependency can cause mood fluctuation, and outlines the psychological benefits of quitting.


The intensification of drug therapy for diabetes and its complications: evidence from 2 HMOs.
To identify trends in the utilization of multidrug therapy for glycemic control, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), and lipid-modifying agents for persons with diabetes from 1997 to 2001. The trends in drug and total expenditures for diabetes patients also were examined. Cross-sectional analysis for each year from 1997 through 2001. Subjects were identified from pharmacy and medical claims data by using Health Employer Data and Information Set diabetes indicator criteria, with the additional criterion that subjects must be receiving drug therapy for diabetes. All subjects were continuously enrolled within the commercial segment of 1 of 2 health maintenance organizations (HMOs) in different geographic areas. The proportion of patients in each year who used multiple antihyperglycemic agents was measured, as was the proportion of diabetes patients receiving ACEI/ARBs or lipid-modifying agents. Drug and total expenditures were estimated for the subjects in each HMO. Both HMOs experienced a substantial growth in the proportion of patients receiving multidrug therapy for glycemic control from 1997 to 2001. HMO 1 saw an increase from 27.1% to 43.4%; the increase in HMO 2 was from 27.3% to 39.6%. The use of ACEI/ARBs and lipid-modifying agents nearly doubled during this time period. Expenditures for drugs increased at a much greater rate than medical expenditures. The intensity of drug therapy for persons with diabetes increased between 1997 and 2001. Consequently, drugs now represent a greater proportion of total expenditures for persons with diabetes.


Anterograde amnesia for Pavlovian fear conditioning and the role of one-trial overshadowing: effects of preconditioning exposures to morphine in the rat.
Four experiments studied anterograde deficits in Pavlovian fear conditioning following prolonged exposure to the mu-opioid receptor agonist morphine. Injections of morphine produced temporally graded anterograde amnesia characterized by deficits in contextual and conditioned-stimulus (CS) conditioning 1 or 7 days and selective impairment in CS conditioning 21 days after last injection. This anterograde deficit in conditioning did not recover across a retention interval, was absent when rats were tested immediately after conditioning, and required the presence of an auditory CS. These results suggest that anterograde deficits in Pavlovian fear conditioning emerged from differences in susceptibility to 1-trial overshadowing of context by CS.


Fresh and weathered crude oil effects on potential denitrification rates of coastal marsh soil.
On April 20, 2010, the Deepwater Horizon oil platform experienced an explosion which triggered the largest marine oil spill in US history, resulting in the release of ∼795 million L of crude oil into the Gulf of Mexico. Once oil reached the surface, changes in overall chemical composition occurred due to volatilization of the smaller carbon chain compounds as the oil was transported onshore by winds and currents. In this study, the toxic effects of both fresh and weathered crude oil on denitrification rates of coastal marsh soil were determined using soil samples collected from an unimpacted coastal marsh site proximal to areas that were oiled in Barataria Bay, LA. The 1:10 ratio of crude oil:field moist soil fully coated the soil surface mimicking a heavy oiling scenario. Potential denitrification rates at the 1:10 ratio, for weathered crude oil, were 46 ± 18.4% of the control immediately after exposure and 62 ± 8.0% of the control following a two week incubation period, suggesting some adaptation of the denitrifying microbial consortium over time. Denitrification rates of soil exposed to fresh crude oil were 51.5 ± 5.3% of the control after immediate exposure and significantly lower at 10.9 ± 1.1% after a 2 week exposure period. Results suggest that fresh crude oil has the potential to more severely impact the important marsh soil process of denitrification following longer term exposure. Future studies should focus on longer-term denitrification as well as changes in the microbial consortia in response to oil exposure.


Prenatal exposure to polycyclic aromatic hydrocarbons and cognition in early childhood.
Epidemiological evidence for gestational polycyclic aromatic hydrocarbon (PAH) exposure and adverse child cognitive outcomes is mixed; little is known about critical windows of exposure. We investigated associations between prenatal PAH exposure and child cognition in a large, multi-site study. We included mother-child dyads from two pooled prospective pregnancy cohorts (CANDLE and TIDES, N = 1,223) in the ECHO-PATHWAYS Consortium. Seven urinary mono-hydroxylated PAH metabolites were measured in mid-pregnancy in both cohorts as well as early and late pregnancy in TIDES. Child intelligence quotient (IQ) was assessed between ages 4-6. Associations between individual PAH metabolites and IQ were estimated with multivariable linear regression. Interaction terms were used to examine effect modification by child sex and maternal obesity. We explored associations of PAH metabolite mixtures with IQ using weighted quantile sum regression. In TIDES, we averaged PAH metabolites over three periods of pregnancy and by pregnancy period to investigate associations between PAH metabolites and IQ. In the combined sample, PAH metabolites were not associated with IQ after full adjustment, nor did we observe associations with PAH mixtures. Tests of effect modification were null except for the association between 2-hydroxynaphthalene and IQ, which was negative in males (βmales = -0.67 [95%CI:-1.47,0.13]) and positive in females (βfemales = 0.31 [95%CI:-0.52,1.13])(pinteraction = 0.04). In analyses across pregnancy (TIDES-only), inverse associations with IQ were observed for 2-hydroxyphenanthrene averaged across pregnancy (β = -1.28 [95%CI:-2.53,-0.03]) and in early pregnancy (β = -1.14 [95%CI:-2.00,-0.28]). In this multi-cohort analysis, we observed limited evidence of adverse associations of early pregnancy PAHs with child IQ. Analyses in the pooled cohorts were null. However, results also indicated that utilizing more than one exposure measures across pregnancy could improve the ability to detect associations by identifying sensitive windows and improving the reliability of exposure measurement. More research with multiple timepoints of PAH assessment is warranted.


Medicaid Patients Travel Disproportionately Farther for Revision Total Joint Arthroplasty.
Access to high-quality care for revision total joint arthroplasty (rTJA) is poorly understood but may vary based on insurance type. This study investigated distance traveled for hip and knee rTJA based on insurance type. A total of 317 revision hips and 431 revision knees performed between 2010 and 2020 were retrospectively reviewed. Cluster sampling was used to select primary hips and knees for comparison. Median driving distance was compared based upon procedure and insurance type. Revision hip and knee patients traveled 18.2 and 11.0 miles farther for surgery compared to primary hip and knee patients (P ≤ .001). For hip rTJA, Medicaid patients traveled farther than Medicare patients followed by commercially insured patients with median distances traveled of 98.4, 67.2, and 35.6 miles, respectively (P = .016). Primary hip patients traveled the same distance regardless of insurance type (P = .397). For knee rTJA, Medicaid patients traveled twice as far as Medicare and commercially insured patients (medians of 85.0, 43.5, and 42.2 miles respectively, P ≤ .046). Primary knee patients showed a similar pattern (P = .264). Age and ASA-PS classification did not indicate greater comorbidity in Medicaid patients. Insurance type may influence rTJA referrals, with disproportionate referral of Medicaid and Medicare patients to nonlocal care centers. In addition to patient burden, these patterns potentially present a financial burden to facilities accepting referrals. Strategies to improve equitable access to rTJA, while maintaining the highest and most economical standards of care for patients, providers, and hospitals, are encouraged.


Aroma dynamic characteristics during the process of variable-temperature final firing of Congou black tea by electronic nose and comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry.
The drying technology is crucial to the quality of Congou black tea. In this study, the aroma dynamic characteristics during the variable-temperature final firing of Congou black tea was investigated by electronic nose (e-nose) and comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC-TOFMS). Varying drying temperatures and time obtained distinctly different types of aroma characteristics such as faint scent, floral aroma, and sweet fragrance. GC × GC-TOFMS identified a total of 243 volatile compounds. Clear discrimination among different variable-temperature final firing samples was achieved by using partial least squares discriminant analysis (R2Y = 0.95, Q2 = 0.727). Based on a dual criterion of variable importance in the projection value (VIP > 1.0) and one-way ANOVA (p < 0.05), ninety-one specific volatile biomarkers were identified, including 2,6-dimethyl-2,6-octadiene and 2,5-diethylpyrazine with VIP > 1.5. In addition, for the overall odor perception, e-nose was able to distinguish the subtle difference during the variable-temperature final firing process.


Surgical and Surgeon-Related Factors Related to Long-Term Survival in Esophageal Cancer: A Review.
Esophagectomy is the mainstay of curative treatment for most patients with a diagnosis of esophageal cancer. This procedure needs to be optimized to secure the best possible chance of cure for these patients. Research comparing various surgical approaches of esophagectomy generally has failed to identify any major differences in long-term prognosis. Comparisons between minimally invasive and open esophagectomy, transthoracic and transhiatal approaches, radical and moderate lymphadenectomy, and high and moderate hospital volume generally have provided only moderate alterations in long-term survival rates after adjustment for established prognostic factors. In contrast, some direct surgeon-related factors, which remain independent of known prognostic factors, seem to influence the long-term survival more strongly in esophageal cancer. Annual surgeon volume is strongly prognostic, and recent studies have suggested the existence of long surgeon proficiency gain curves for achievement of stable 5-year survival rates and possibly also a prognostic influence of surgeon age and weekday of surgery. The available literature indicates a potentially more critical role of the individual surgeon's skills than that of variations in surgical approach for optimizing the long-term survival after esophagectomy for esophageal cancer. This finding points to the value of paying more attention to how the skills of the individual esophageal cancer surgeon can best be achieved and maintained. Careful selection and evaluation of the most suitable candidates, appropriate and structured training programs, and regular peer-review assessments of experienced surgeons may be helpful in this respect.


Supernumerary proteins of mitochondrial ribosomes.
Messenger RNAs encoded by mitochondrial genomes are translated on mitochondrial ribosomes that have unique structure and protein composition compared to prokaryotic and cytoplasmic ribosomes. Mitochondrial ribosomes are a patchwork of core proteins that share homology with prokaryotic ribosomal proteins and new, supernumerary proteins that can be unique to different organisms. In mammals, there are specific supernumerary ribosomal proteins that are not present in other eukaryotes. Here we discuss the roles of supernumerary proteins in the regulation of mitochondrial gene expression and compare them among different eukaryotic systems. Furthermore, we consider if differences in the structure and organization of mitochondrial genomes may have contributed to the acquisition of mitochondrial ribosomal proteins with new functions. The distinct and diverse compositions of mitochondrial ribosomes illustrate the high evolutionary divergence found between mitochondrial genetic systems. Elucidating the role of the organism-specific supernumerary proteins may provide a window into the regulation of mitochondrial gene expression through evolution in response to distinct evolutionary paths taken by mitochondria in different organisms. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.