Corrigendum to "Which factor is more important for the welfare of broiler chickens: Intensity or duration of episodic heat stress?" [J. Therm. Biol. 99 (2021) 102981].
Due to the effects of global warming, there is a predicted increase in the frequency, intensity and duration of heat waves in the future. Little is known of how this could affect the welfare of broiler chickens. Sixty-four broiler chickens were subjected to either high heat stress (HHS; 32oC, 70% RH for 3 h), moderate heat stress (MHS; 30oC, 70% RH for 6 h), or normal conditions (NC: 20oC, 50% RH for 6 h) for two consecutive days. Half the birds had been subjected to anaesthesia and fitted with a body temperature-ID chip placed in the breast muscle. Core body temperature (CBT) was taken during pre-heat stress (PrHS), at the end of 3 h (3HS) and 6 h (6HS) of heat stress using a pocket reader and used to estimate change in CBT (ΔCBT). Surface body temperatures (SBTs) from under the wing (WT), feet (FT), cloaca (CLT) and comb (CT) were also measured, along with blood parameters, feed intake, daily weight gain and mortality. Data were analysed using General Linear Model and simple linear regression. At 3HS, CBT/ΔCBT and all SBTs showed this trend: HHS > MHS > NC (P<0.001). Blood pH, pCO2, iCa, HCO3- and TCO2 showed the same trend: HHS, MHS > NC (P<0.05). Comparing HHS for 3 h with MHS and NC for 6 h showed that CBT/ΔCBT, WT and CLT in HHS, MHS > control (P<0.001) while FT and CT showed a different trend (HHS > MHS > NC, P<0.001). Exposure of broiler chickens to 3 hours of HHS had dramatic effects on core and surface body temperatures. The effects of MHS were initially more modest yet, after a further 3 hours exposure, resulted in an increase in CBT which was close to that which HHS birds experienced after just 3 hours. This illustrates that duration of exposure to heat stress can have a critical effect, achieving similar life-threatening changes in body temperature that were observed under higher levels of heat stress but for half the time.


DNA-based aptamer fails as a simultaneous cancer targeting agent and drug delivery vehicle for a phenanthroline-based platinum(II) complex.
The sgc8c aptamer is a 41-base DNA oligonucleotide that binds to leukaemia cells with high affinity and specificity. In this work we examined the utility of this aptamer as both a delivery vehicle and an active targeting agent for an inert platinum complex [(1,10-phenathroline)(ethylenediamine)platinum(II)](2+). The aptamer forms a stem-and-loop confirmation as determined by circular dichroism. This conformation is adopted in both water and phosphate buffered saline solutions. The metal complex binds through intercalation into the aptamer's double helical stem with a binding constant of approximately 4.3 × 10(4) M(-1). Binding of the metal complex to the aptamer had a significant effect on the aptamer's global conformation, and increased its melting temperature by 28°C possibly through lengthening and stiffening of the aptamer stem. The effect of the aptamer on the metal complex's cytotoxicity and cellular uptake was determined using in vitro assays with the target leukaemia cell line CCRF-CEM and the off-target ovarian cancer cell lines A2780 and A2780cp70. The aptamer has little inherent cytotoxicity and when used to deliver the metal complex results in a significant decrease in the metal complex's cytotoxicity and uptake. The reason(s) for the poor uptake and activity may be due to the change in aptamer conformation which affects its ability to recognise leukaemia cells.


Predictability of refraction following immediate sequential bilateral cataract surgery (ISBCS) performed under general anaesthesia.
To evaluate the predictability of refraction following immediate sequential bilateral cataract surgery (ISBCS) performed under general anaesthesia. This is a retrospective review of all ISBCS performed at Kantonsspital Winterthur, Switzerland, between April 2000 and September 2013. The case notes of 250 patients were reviewed. Patients having full refraction reported (110 patients/220 eyes) were included. 210 (95 %) eyes had a straight forward phacoemulsification with posterior chamber intraocular lens implantation, seven eyes had a planned extracapsular cataract extraction (ECCE); three eyes had an intracapsular cataract extraction. Both eyes of 110 patients (64 women, 46 men) with a mean age of 79.0 years, standard deviation (SD) ±11.4 (range 26 to 97 years) were included. Median preoperative best corrected visual acuity (BCVA) was 0.5 LogMAR in the first eye, the interquartile range (IQR) was [0.4, 1.2]; 0.7 LogMAR in the second eye with IQR [0.4, 1.8]. At one month, the median BCVA was 0.2 LogMAR, IQR [0.1, 0.3] in the first eye, median BCVA was 0.1 LogMAR and IQR [0.0, 0.5] in the second eye. There were 3 eyes (3 %) that lost 3 lines or more in BCVA at one month (control vs. pre-operatively). In all three cases, poor visual acuity had been recorded pre-operatively (>1 LogMAR). Achieved refraction was within ±1.0 D of the target in 83 % of eyes. There were only 5 % (n = 6) of cases where if delayed sequential bilateral extraction had been performed could potentially intraocular lens (IOL) choice have been adjusted, in four of these cases, target refraction was within ±1.0 D in the second eye. ISBCS performed under general anaesthesia achieves target refraction in 83 % of eyes after consideration of complications, ocular co-morbidities and systemic restrictions. In the majority of cases where IOL power calculation could be considered, the achieved refraction of the second surgical eye was within ±1.0 D of intended refraction. This undermines the utility of IOL power adjustments in the second surgical eye.


Effectiveness of ultrasonographic skeletal muscle assessment in patients after total knee arthroplasty.
This study aimed to characterize the skeletal muscles of patients who underwent total knee arthroplasty (TKA) using ultrasonography in order to investigate the effectiveness of ultrasonographic skeletal muscle assessment after TKA. This study included 50 TKA patients (TKA group) and 41 residents with osteoarthritis who have not received TKA (non-TKA group). Ultrasonography was used to assess the characteristics of several different muscles. Various postoperative outcomes were evaluated. Muscle thickness (MT) and echo intensity (EI) results were compared among operated knees in the TKA group, nonoperated knees in the TKA group, and more severely affected knees in the non-TKA group. For the TKA group, multiple regression was conducted to examine the association between skeletal muscle characteristics of operated knees and postoperative outcomes. The MTs of the vastus medialis, vastus intermedius, and rectus femoris (RF) were significantly smaller and the RF-EI was significantly greater for both operated and nonoperated knees in the TKA group compared with the non-TKA group (P < 0.017). Several parameters of physical function were significantly poorer in the TKA group than in the non-TKA group (P < 0.05). Multiple regression demonstrated that RF-MT was associated with knee range of motion, knee strength, and physical functional performance in the TKA group (P < 0.05). The quantity and quality of skeletal muscles were lower in the TKA group than in the non-TKA group. Ultrasonography may be useful for assessing skeletal muscles in TKA patients because MT assessed with ultrasonography was associated with various parameters of physical function.


Whole body de novo amino acid synthesis in type I (insulin-dependent) diabetes studied with stable isotope-labeled leucine, alanine, and glycine.
Dynamic aspects of whole body alanine and glycine metabolism have been explored in insulin-dependent (type I) diabetic subjects. Using a primed, continuous intravenous (i.v.) infusion of [2H3]alanine and [15N]glycine given simultaneously with [1-13C]leucine, whole body alanine and glycine fluxes and their rates of de novo synthesis were measured in 6 diabetic young men. Subjects were studied in the postabsorptive state, after blood glucose was clamped overnight at 15.2 +/- 0.3 mM, and then, on the following night, at 5.9 +/- 0.2 mM (insulin infusion rates of 0.24 +/- 0.09 and 1.65 +/- 0.20 U/h, respectively). In the normoglycemic state, leucine, alanine, and glycine fluxes averaged 88 +/- 4, 378 +/- 39, and 155 +/- 8 mumol X kg-1 X h-1, respectively. Based on the leucine flux, alanine and glycine de novo synthesis rates were 264 +/- 36 and 67 +/- 8 mumol X kg-1 X h-1. In the hyperglycemic state, leucine flux increased 23% (P less than 0.01), alanine flux rose slightly (+5%) but significantly (P less than 0.05), while alanine de novo synthesis and glycine flux remained unchanged and glycine de novo synthesis decreased by 33% (P less than 0.001). These results show that small alterations in peripheral alanine inflow in the hyperglycemic state reflect increased proteolysis and suggest that increased circulating plasma glucose does not contribute to de novo alanine synthesis in the absence of adequate insulin effect and/or augmented glucose tissue uptake. These observations also reveal the importance of insulin in the maintenance of whole body leucine economy, since a lower rate of insulin administration was associated with an increased rate of leucine oxidation.


Dedifferentiated liposarcoma lung metastases with different FDG-PET/CT findings.
Dedifferentiated liposarcoma (DDLPS) is a rare tumor and generally shows poor prognosis with the lung frequent metastatic site. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used for staging or metastatic evaluation of this disease. We report a case of bilateral lung metastases of DDLPS showing uncommon imaging on FDG-PET/CT with completely different FDG uptake, which made preoperative diagnosis difficult. The patient was a male in his 60 s and bilateral lung nodules were noted after proton beam therapy for retroperitoneal DDLPS. FDG-PET/CT showed high FDG uptake in the left S3 15-mm nodule but no uptake in the right S8 10-mm nodule. Thoracoscopic wedge resection for the left nodule was performed, and the pathology revealed metastasis of dedifferentiated liposarcoma. After resection of the left nodule, the right S8 nodule enlarged without FDG uptake. Thoracoscopic right S8 segmentectomy was performed, and metastasis of dedifferentiated liposarcoma was diagnosed. The 2 tumors showed completely different appearances on FDG-PET/CT with similar histopathological findings. We encountered a case of multiple pulmonary metastases of DDLPS which did not follow the same imaging appearance on FDG-PET/CT. Appropriate timing of surgical resection for pathological diagnosis should be determined carefully.


Initial Clinical Outcome With Bilateral, Dual-Target Deep Brain Stimulation Trial in Parkinson Disease Using Summit RC + S.
Deep brain stimulation (DBS) is an effective therapy in advanced Parkinson disease (PD). Although both subthalamic nucleus (STN) and globus pallidus (GP) DBS show equivalent efficacy in PD, combined stimulation may demonstrate synergism. To evaluate the clinical benefit of stimulating a combination of STN and GP DBS leads and to demonstrate biomarker discovery for adaptive DBS therapy in an observational study. We performed a pilot trial (n = 3) of implanting bilateral STN and GP DBS leads, connected to a bidirectional implantable pulse generator (Medtronic Summit RC + S; NCT03815656, IDE No. G180280). Initial 1-year outcome in 3 patients included Unified PD Rating Scale on and off medications, medication dosage, Hauser diary, and recorded beta frequency spectral power. Combined DBS improved PD symptom control, allowing >80% levodopa medication reduction. There was a greater decrease in off-medication motor Unified PD Rating Scale with multiple electrodes activated (mean difference from off stimulation off medications -18.2, range -25.5 to -12.5) than either STN (-12.8, range -20.5 to 0) or GP alone (-9, range -11.5 to -4.5). Combined DBS resulted in a greater reduction of beta oscillations in STN in 5/6 hemispheres than either site alone. Adverse events occurred in 2 patients, including a small cortical hemorrhage and seizure at 24 hours postoperatively, which resolved spontaneously, and extension wire scarring requiring revision at 2 months postoperatively. Patients with PD preferred combined DBS stimulation in this preliminary cohort. Future studies will address efficacy of adaptive DBS as we further define biomarkers and control policy.


Effects of stigma on the mental health of adolescents orphaned by AIDS.
By 2010, an estimated 18.4 million children in Sub-Saharan Africa will be orphaned by AIDS. Research in South Africa shows that AIDS orphanhood is independently associated with heightened levels of psychological problems. This study is the first to explore the mediating effects of stigma and other factors operating on a community level, on associations between AIDS orphanhood and mental health. We assessed the associations of four risk factors that can potentially be addressed at a community level (bullying, stigma, community violence, and lack of positive activities) with psychological problems and orphanhood status. One thousand twenty-five participants aged 10-19 were recruited from deprived urban settlements in South Africa. The sample included adolescents orphaned by AIDS (n = 425), adolescents orphaned by non-AIDS causes (n = 241), and nonorphaned adolescents (n = 278). Participants were interviewed using standardized psychological measures of depression, anxiety, posttraumatic stress, peer problems, delinquency, and conduct problems. Information on risk factors and demographic characteristics were also assessed. AIDS-orphaned adolescents reported higher levels of stigma and fewer positive activities than other groups. There were no reported differences on bullying or community violence. All community-level risk factors were associated with poorer psychological outcomes. Multivariate analyses controlling for age and gender showed that experience of stigma significantly mediated associations between AIDS orphanhood and poor psychological outcomes. Reduction of AIDS-related stigma could potentially reduce adverse psychological outcomes among AIDS-orphaned adolescents.


Preventive intraperitoneal hyperthermic perfusion chemotherapy for patients with T4 stage colon adenocarcinoma.
Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be an effective treatment for peritoneal tumors; whether preventive HIPEC after radical resection for T4 stage colon adenocarcinoma could decrease peritoneal recurrence remains unknown. The aim of the present study was to compare peritoneal recurrence and short-term survival in patients with T4 stage colon adenocarcinoma undergoing HIPEC plus adjuvant chemotherapy or adjuvant chemotherapy alone following surgery. We retrospectively reviewed T4 stage colon adenocarcinoma patients who had radical tumor resection at our institution between January 2014 and January 2019. Clinical data were extracted from the database at our institution, and patient survival and long-term complications were assessed through repeated outpatient examinations and telephone interviews. A total of 352 patients were included in this study; 157 patients received postoperative HIPEC plus adjuvant chemotherapy (HIPEC group), 195 patients received adjuvant chemotherapy alone (conventional chemotherapy group). Forty-one (26.1%) patients in the HIPEC group had a peritoneal recurrence and the peritoneum was the first site of tumor recurrence in 6 (14.6%) of them. However, 73 (37.4%) patients experienced peritoneal recurrence in the conventional group, and the peritoneum was the first site of tumor recurrence in 25 (34.2%) (p = 0.019). Disease-free survival in the HIPEC group at 1 and 3 years was 93.3% and 61.1%, respectively, versus 89.3% and 51.7% in the conventional chemotherapy group (p = 0.038). Overall survival in the HIPEC group at 1 and 3 years was 100.0% and 82.7%, respectively, versus 100.0% and 76.9% in the conventional chemotherapy group (p = 0.420). The two groups did not differ with respect to severe complications. Preventive HIPEC after radical surgery may decrease peritoneal recurrence and promote disease-free survival for T4 stage colon adenocarcinoma. Large-scale randomized controlled studies are needed to confirm the results of our study.


Stability of 111In-bleomycin in vivo--properties compared with 57Co-bleomycin.
111Indium-bleomycin (111In-BLM) and 57Co-bleomycin (57Co-BLM) were prepared and their distributions were compared in the tissues, blood, and urine in tumor-bearing and in untreated mice and rats. Autoradiographs of electrophoresis gels showed that patterns for urine from untreated and tumor-bearing animals, collected 1-3 h or 48 h after injection of 111In-BLM were similar to those for in vitro mixtures of urine and 111In-BLM, but differed from the patterns obtained with 111InCl3 under in vivo or in vitro conditions. In rats bearing mammary adenocarcinoma, 48 h after administration of the radiopharmaceutical, the activity ratio of tumor to eleven different tissues was 1.2-4.6 times higher for injected 111In-BLM than for 111InCl3 (P less than or equal to 0.001 or P less than or equal to 0.05). Imaging with a gamma camera depicted tumors in mice more distinctly with 111In-BLM than with 111InCl3. These findings were interpreted as reflecting the stability of 111In-BLM in vivo. The tumor concentration (%dose/g) was higher for the viable area than for the necrotic area for 111In-BLM, but the reverse was true for 57Co-BLM.


Exertional rhabdomyolysis in a 4-year-old standardbred filly.
A young standardbred filly became stiff and uncomfortable after racing. A day later, creatine kinase, aspartate aminotransferase, and lactic dehydrogenase levels were markedly elevated. Exertional rhabdomyolysis was diagnosed. Limited exercise and a low carbohydrate, high fat diet were prescribed. Eight days later, the filly was raced again without consequences.


Investigating the role of task relevance during rhythmic sampling of spatial locations.
Recently it has been discovered that visuospatial attention operates rhythmically, rather than being stably employed over time. A low-frequency 7-8 Hz rhythmic mechanism coordinates periodic windows to sample relevant locations and to shift towards other, less relevant locations in a visual scene. Rhythmic sampling theories would predict that when two locations are relevant 8 Hz sampling mechanisms split into two, effectively resulting in a 4 Hz sampling frequency at each location. Therefore, it is expected that rhythmic sampling is influenced by the relative importance of locations for the task at hand. To test this, we employed an orienting task with an arrow cue, where participants were asked to respond to a target presented in one visual field. The cue-to-target interval was systematically varied, allowing us to assess whether performance follows a rhythmic pattern across cue-to-target delays. We manipulated a location's task relevance by altering the validity of the cue, thereby predicting the correct location in 60%, 80% or 100% of trials. Results revealed significant 4 Hz performance fluctuations at cued right visual field targets with low cue validity (60%), suggesting regular sampling of both locations. With high cue validity (80%), we observed a peak at 8 Hz towards non-cued targets, although not significant. These results were in line with our hypothesis suggesting a goal-directed balancing of attentional sampling (cued location) and shifting (non-cued location) depending on the relevance of locations in a visual scene. However, considering the hemifield specificity of the effect together with the absence of expected effects for cued trials in the high valid conditions we further discuss the interpretation of the data.


Hospital incidence, mortality and costs of Alzheimer's disease in Spain: a retrospective multicenter study.
Alzheimer's disease (AD) is the most common form of dementia. Its neurodegenerative nature and the lack of a curative treatment result in a substantial burden for healthcare systems and society. This study aimed to analyze the hospital incidence and mortality of AD in Spain and to evaluate patients' use of healthcare resources and direct medical costs. Admission records of patients with AD treated in hospitals in Spain between 2011 and 2016 were selected from a Spanish hospital discharge database. Records of 7,894 patients with diagnosed AD were analyzed. Hospital incidence was 3.7 per 10,000 persons over the study period, 2.9 and 4.4 for males and females, respectively. In-hospital mortality was 9.5%; both hospital incidence and in-hospital mortality increased over the study period. Mortality was principally associated with acute respiratory failure and other diseases of the respiratory system and heart failure. Annual medical costs of specialized care increased slightly during the study period, with a mean annual cost per patient of €4,969. AD is responsible for an increasing proportion of hospitalizations in Spain and raising medical costs, which highlights the importance of early detection and optimized care.


Targeting B cell leukemia with highly specific allogeneic T cells with a public recognition motif.
The possibility that allogeneic T cells may be targeted to leukemia has important therapeutic implications. As most tumor antigens represent self-proteins, high-avidity tumor-specific T cells are largely deleted from the repertoire of the patient. In contrast, T cells from major histocompatibility complex (MHC)-mismatched donors provide naïve repertoires wherein such cells have not been systematically eliminated. Yet, evidence for peptide degeneracy or poly-specificity warrants caution in the use of foreign human leukocyte antigen (HLA) or peptide complexes as therapeutic targets. Here, we cocultured HLA-A(*)0201-negative T cells with autologous dendritic cells engineered to present HLA-A(*)0201 complexed with a peptide from the B cell antigen CD20 (CD20p). HLA-A(*)0201/CD20p pentamer-reactive CD8(+) T cells were readily obtained from all donors. The polyclonal cells showed exquisite peptide and MHC specificity, and efficiently killed HLA-A(*)0201-positive B cells, including primary chronic lymphocytic leukemia cells. The T cell receptor (TCR) sequences displayed a novel type of conservation, with extensive homology in the TCR β chain complementarity-determining region 3 and in J, but not V, region. This is surprising, as the donors were HLA disparate and their TCR repertoires are expected to show little overlap. The results demonstrate the first public recognition motif for an allogeneic HLA/peptide complex. The allo-restricted T cells or TCRs could provide graft-versus-leukemia in the absence of graft-versus-host disease.


Salvage of post-traumatic arthritis following distal radius fracture.
There are practical recommendations that can be drawn from the aforementioned results. Due to the minimal morbidity of the wrist denervation, patients with good but painful wrist motion following fracture of the distal radius should first be evaluated for wrist denervation unless formal resection of the dorsal interosseous nerve has clearly been included in the previous treatment. The evaluation is performed in a standardized manner before and after test infiltration of both interosseous nerves. This evaluation includes assessment of pain, strength, and working capacity. Whereas the grip strength often does not (cannot)increase more than 10% to 20%, the subjective pain relief can be remarkable, leading to higher repetition counts and increased dexterity. Inpatients with insufficient response to the anesthetic nerve blocks, other pain sources must be sought, especially on the ulnar side of the wrist. Patients with less than functional range are candidates for complete arthrodesis. A way for further evaluation with regard to the potential of partial and complete wrist arthrodesis is trial immobilization of the wrist in a light cast ora firm reinforced brace. Trial immobilization also allows anticipating the functional deficit from loss of range of wrist motion. Due to the still-unrestricted pronation and supination, ulnar-sid-ed wrist pain may persist and will need adequate follow-up adjunct treatment. Patients who have good pain relief but are not willing to completely lose their wrist motion should be evaluated fluoroscopically or receive lateral radiographs in full flexion and extension to measure their mid-carpal joint mobility and anticipate the potential residual motion after radiocarpal fusion. Patients without pain relief from test anesthesia, trial immobilization, and no apparent distal radioulnar joint pathology are poor candidates for further operative treatment.In evaluating different salvage procedures,among all diagnoses, painful arthritis following fracture of the distal radius is the most difficult to treat and yields the poorest results. Emphasis must therefore be on better initial fracture treatment and earlier secondary reconstructive interventions. The current salvage procedures must allow further improvement or alternatives must be developed. Prosthetic replacement merits serious consideration, especially when it can be adapted to the specific post-traumatic setting. This situation is not worse than rheumatoid arthritis because the clinician is dealing with healthy and strong intact bone stock, tendons, and ligaments,and most important, complete absence of a progressive disease.


Information scrambling in quantum circuits.
Interactions in quantum systems can spread initially localized quantum information into the exponentially many degrees of freedom of the entire system. Understanding this process, known as quantum scrambling, is key to resolving several open questions in physics. Here, by measuring the time-dependent evolution and fluctuation of out-of-time-order correlators, we experimentally investigate the dynamics of quantum scrambling on a 53-qubit quantum processor. We engineer quantum circuits that distinguish operator spreading and operator entanglement and experimentally observe their respective signatures. We show that whereas operator spreading is captured by an efficient classical model, operator entanglement in idealized circuits requires exponentially scaled computational resources to simulate. These results open the path to studying complex and practically relevant physical observables with near-term quantum processors.


Cloud point extraction of carbendazim fungicide from strawberry samples and amperometric detection with boron doped diamond.
The cloud point extraction (Tergitol® surfactant) method was used for the first time to extract and preconcentrate the fungicide carbendazim (CBZ) from strawberry samples, while electrochemical detection (boron doped diamond electrode) in association with high performance liquid chromatography (HPLC-EC) was used for the determination of CBZ. The variables of bath temperature, ultrasonic stirring time, mass of NaCl and amount of surfactant were investigated using a 24 full factorial design. Limits of detection (LOD, S/N = 3) and quantification (LOQ) of 3.42 × 10-8 mol/L (or 6.54 µg/L) and 6.84 × 10-8 mol/L (or 13.1 µg/L), respectively, were obtained for the CPE processes, considering the value of the preconcentration factor obtained (9.12). The method was validated based on linearity, intra-day and inter-day recovery tests, accuracy and precision. The proposed method was applied to strawberry samples from local commercial establishments and different procedures for washing and sanitizing strawberry fruits were also evaluated.


Sexual behaviour: a receptor for sex control in Drosophila females.
Male Drosophila manipulate the sexual behaviour of their female mating partners by release of a Sex-peptide, but how does this work? A G-protein-coupled receptor has now been identified which acts in the female flies to detect male Sex-peptide and trigger increased egg laying and reduced sexual receptivity.


Malignant peritoneal cytologic contamination with robotic hysterectomy for endometrial cancer.
Malignant peritoneal cytology in endometrial cancer (EC) is not considered an independent adverse prognostic factor for uterine-confined disease and is not a determinant factor in the International Federation of Gynecology and Obstetrics (FIGO) staging system. NCCN Guidelines still recommend obtaining cytologies. The aim of this study was to determine the prevalence of peritoneal cytologic contamination following robotic hysterectomy for EC. Peritoneal cytology from the pelvis and diaphragm were obtained at the initiation of surgery, and from the pelvis only at the completion of robotic hysterectomy with sentinel lymph node mapping (SLNM). Cytology specimens were evaluated for the presence of malignant cells. Pre- and post-hysterectomy cytology results were compared, and pelvic contamination was defined as conversion from negative to positive cytology following surgery. 244 patients underwent robotic hysterectomy with SLNM for EC. Pelvic contamination was identified in 32 (13.1%) cases. In multivariate analysis, pelvic contamination was associated with >50% myometrial invasion, tumor size >2 cm, lymphovascular space invasion (LVSI), and lymph node metastasis. There was no association with FIGO stage or histology subtypes. Malignant peritoneal contamination occurred during robotic surgery for EC. Large lesions (>2 cm), deep invasion (>50%), LVSI, and lymph node metastasis were each independently associated with peritoneal contamination. Whether or not peritoneal contamination increases risk for disease recurrence should be studied in larger series, including an evaluation of patterns of recurrence and the potential impact of adjuvant therapies. Until the clinical impact of peritoneal contamination during hysterectomy for EC is better understood, methods to reduce peritoneal contamination are warranted.


Glucocorticoid treatment of girls with congenital adrenal hyperplasia: effects on height, sexual maturation, and fertility.
Ninety-eight females with congenital adrenal hyperplasia due to a defect in either the 21-hydroxylase or the 11 beta-hydroxylase enzyme were evaluated to determine the effects of glucocorticoid treatment on growth, pubertal development, and fertility. When treatment was begun prior to one year of age, mean final height was 157.4 +/- 7.3 com, well within the normal adult female range, and significantly (p less than 0.001) greater than the mean final height of 150.9 +/- 4.3 cm found in untreated patients. The mean age of menarche in patients treated prior to the age of six years was 13.8 +/- 3.7 years which is significantly (p less than 0.01) delayed compared to that in the normal population of the United States. However, 92% of patients with menstrual delay had inadequate suppression of adrenal androgens and urinary excretion of 17 ketosteroids larger than 7.0 mg/24hours. The increased production of adrenal androgens was the result of poor compliance or an insufficient prescribed dose of glucocorticoids. The fertility rate in patients first treated between six and 20 years of age was 64%. The excretion of urinary 17 KS at the time of pregnancy was 2.5 to 5.3 mg/24 hours. All of the patients who delivered term infants required delivery by cesarean section because of cephalopelvic disproportion. The major problems encountered in the management of adolescent patients were patient noncompliance and physician failure to increase the glucocorticoid dose as the patient's body size increased.


Choice of an aqueous polymer two-phase system for cell partition.
Partition of human erythrocytes in aqueous two-phase polymer systems produced by Ficoll and different molecular weight fractions of dextran and polyethylene glycol and the influence of the ionic composition on the cells' partition in the systems was studied. It is found that the Ficoll-dextran-40 system is characterized by a number of advantages as compared with the common dextran-polyethylene glycol system or the others systems under study. The main advantage of the system appears to be that it is possible to concentrate the red cells in the top phase or in the bottom phase of the system, depending on the system ionic composition. The influence of the nature and the concentration of salt additives on this two-phase system formation is examined.


Risk factors for epistaxis on British racecourses: evidence for locomotory impact-induced trauma contributing to the aetiology of exercise-induced pulmonary haemorrhage.
The proposed biological mechanisms for exercise-induced pulmonary haemorrhage (EIPH) are many and varied. Better knowledge of risk factors should lead to achievable measures to reduce the incidence. To identify risk factors associated with epistaxis following racing in UK Thoroughbreds, to gain possible insights into the pathogenesis of the condition and to investigate the association between epistaxis and race finishing position. The association of epistaxis occurring on UK racecourses between 1996 and 1998 with a wide range of race-, horse- and start-level variables was examined in multivariable mixed effect logistic regression analyses. Four multivariable analyses were conducted, one for all race types considered collectively and one each for flat, hurdle and steeplechase race types considered separately. Risk of epistaxis was significantly increased for hurdle and steeplechase race types compared to both flat and National Hunt flat races. In 3 of the 4 final models, there was a significant biological trend for increasing risk of epistaxis with increasing ground hardness ('going') and accumulated years spent racing. However, in flat races epistaxis was such a rare outcome (0.33 cases per 1000 starts) that this subset analysis had insufficient power to measure the detectable effect of 'going' as statistically significant. Horses with epistaxis were significantly more likely to have a poorer finishing position than those without blood at the nostrils. Findings were consistent with the theory that locomotory impact-induced trauma contributes to exercise-induced epistaxis. Further validation of this hypothesis through application of similar methods to endoscopically visible EIPH and through biomechanical studies is warranted. Knowledge of significant risk factors should allow formulation of practical measures, such as track watering, to reduce the risks of EIPH and epistaxis in racehorses.


Cleft Lip Nose.
All patients with a cleft lip deformity have an associated nasal deformity that varies in degree of severity. A three-dimensional understanding of the anatomy of the cleft nose aids surgeons in selecting the proper technique for repair. Analysis and performance of orthognathic surgery should be done before nasal surgery to optimize the overall result. Goals of the secondary rhinoplasty include relief of nasal obstruction, creation of symmetry and definition of the nasal base and tip, and management of nasal scarring and webbing. Septal reconstruction in the cleft nose is a key maneuver in cleft rhinoplasty.


Left ventricular filling patterns and its relation to left ventricular untwist in patients with type 1 diabetes and normal ejection fraction.
We evaluated young patients with type 1 diabetes (T1DM) who had normal left ventricular (LV) ejection fraction and used speckle tracking echocardiography to assess changes in LV untwisting. We used cardiac magnetic resonance imaging (MRI) to assess the LV filling patterns in these subjects. We recruited 33 T1DM patients and 32 age-matched healthy controls (HC) into the study. Study participants underwent echocardiography, cardiac MRI and metabolic exercise testing. The early peak LV untwisting rate (E) was similar in T1DM and HC (-11.9 ± 4.6 0/cm/s vs -11.3 ± 4.7 0/cm/s, P=0.29) but the late peak LV untwisting rate (A) was significantly increased in T1DM (-6.2 ± 3 0/cm/s vs -4.9 ± 3.9 0/cm/s, P<0.05). The time to early peak untwisting rate was not different (50.9 ± 9.6% vs 48.4 ± 7.3%, P=0.12) but the time to late peak untwisting rate was significantly delayed in T1DM patients (80.4 ± 12.5% vs 72.7 ± 14.6%, P<0.05). The LV filling patterns demonstrated a significantly increased left atrial (LA) contribution to LV filling in T1DM. On linear regression peak late filling rate (r=0.60, P<0.000), trans-mitral A wave (r=0.25, P<0.05) and A' (r=0.30, P<0.01) were predictors of LA contribution to LV filling. We demonstrate for the first time using speckle tracking that LV untwisting rate E is preserved and untwisting rate A is increased and delayed in young patients with uncomplicated T1DM. The LA contribution to LV filling is increased in these patients and is directly related to increases in other indices of LA function like peak late filling rate, trans-mitral A wave and A'.


The development of the intercondylar notch in the pediatric population.
Anterior cruciate ligament (ACL) repair is increasing in frequency in younger children. Recognition of the normal development of the intercondylar notch is important for successful ACL graft placement, allowing surgeons to better understand the anatomy and risk factors related to ACL tears and its reconstruction. The purpose of this study was to compile normative data on the intercondylar notch in the pediatric population with magnetic resonance imaging (MRI), emphasizing the differences between males and females. In this retrospective study, musculoskeletal radiologists evaluated intercondylar notch width, bicondylar distance and notch width index (NWI). A total of 253 MRI examinations (130 males and 123 females between six and 18 years of age) were included. The association between measurements, sex and age was considered. Linear and fractional polynomial regression models were used to evaluate the relationships between measurements. Intercondylar notch width increased up to 10 years of age in females and 11 years of age in males, with relative stabilization up to 13 years in girls and 14 years in boys and a slight reduction in values at subsequent ages. Bicondylar distance showed significant progressive growth with age in both sexes. NWI showed a discrete and homogenous reduction with age in both sexes. Intercondylar notch width interrupts its growth around 10-11 years of age, with relative stabilization up to 13-14 years and a slight reduction in dimensions in subsequent ages. This growth pattern resembles the development of the ACL area observed in recent studies.


Removal of parotid, submandibular, and sublingual glands.
Surgical removal of the major salivary glands is a common task for the oral and maxillofacial surgeon. The major salivary glands have complex anatomic relationships with the surrounding neurovascular structures, and a thorough understanding of the surgical anatomy is essential for any surgeon involved in the management of salivary gland disease. This article reviews the indications, surgical anatomy, diagnostic evaluation, and surgical techniques for removal of the major salivary glands.


Sivelestat reduces inflammatory mediators and preserves neutrophil deformability during simulated extracorporeal circulation.
Neutrophil is a major focus in efforts to ameliorate the systemic inflammatory response associated with cardiopulmonary bypass. Neutrophil elastase is a powerful proteolytic enzyme, and plays a pivotal role in the development of the inflammatory response. This study assesses the inhibitory effects of sivelestat, a highly specific neutrophil elastase inhibitor, on elastase levels, cytokine production, and the functional changes of neutrophils in a simulated extracorporeal circulation model. Simulated recirculation was established by recirculating heparinized (3.75 U/mL) human blood for 120 minutes in an oxygenator and a roller pump circuit with and without 100 micromol/L of sivelestat (n = 7 for each group). Neutrophil elastase and interleukin-8 were measured with an enzyme immunoassay. Neutrophil deformability was evaluated by simulated microcapillaries. The neutrophil F-actin and the expression of CD11b and L-selectin were measured by flow cytometry. Sivelestat reduced both neutrophil elastase levels (p = 0.0006) and interleukin-8 production (p < 0.0001) at 120 minutes of recirculation. Sivelestat also significantly preserved neutrophil deformability (p = 0.017) and reduced F-actin expression (p = 0.0037). The drug did not modulate the changes of CD11b or L-selectin. This study suggests that specific elastase inhibition with sivelestat could be a feasible therapeutic strategy for patients undergoing cardiopulmonary bypass to attenuate neutrophil-derived inflammatory response and organ injuries.


Medical home disparities are not created equal: differences in the medical home for children from different vulnerable groups.
To identify components of the medical home that contribute to medical home disparities for vulnerable children. Cross-sectional analysis of 2007 National Survey of Children's Health. Prevalence of components of the medical home were estimated by special health care needs (SHCN), race/ethnicity, primary language, and health insurance. Medical home disparities for children with SHCN were driven by differences in getting help with care coordination, when needed (71% vs. 91% children without SHCN, p<.001). Medical home disparities for other groups were largely attributable to less family-centered care (Hispanic 49% and African American 55% vs. White 77%, p<.001; non-English primary language 37% vs. English 72%, p<.001; uninsured 45% and publicly insured 57% vs. privately insured 75%, p<.001). The components of the medical home that contribute to medical home disparities differ between groups of vulnerable children. Medical home implementation may benefit from focusing on the specific needs of target populations.


Characterization of a laminar flow cell for the prevention of biosensor fouling.
A flow cell using dual parallel laminar flows was designed and fabricated with the aim to prevent biosensor fouling. Y-shaped entrances allowed the introduction of sample and electrolyte streams, with the electrolyte serving as a mobile protective layer near the biosensor. Potassium permanganate was used to quantify the diffusion in the flow cell. Optical intensity analysis of potassium permanganate along a series of transverse lines across the flow cell was carried out under different flow conditions. It was found that the error function, erf(y/[square root](Dt)), where y was the position along the transverse line, D the diffusion coefficient of the solute and t was the time, gave reasonable approximation to the diffusion of potassium permanganate in the cell. The diffusion coefficient of potassium permanganate was determined in stop-flow measurements and the value, D=4.0 x 10(-5)cm(2)/s, agreed to previously reported values. Velocity distribution in the flow cell was simulated numerically to reveal the development of two inflows into one single laminar flow. Results from the study provided preliminary data on solute diffusion characteristics in the flow cell and supported the working principle of laminar flow cells in preventing biosensor fouling.


Gene deregulation in gastric cancer.
Despite its decreasing frequency in the Western world during recent decades, gastric cancer is still one of the leading causes of cancer-related deaths worldwide. Due to the oligosymptomatic course of early gastric cancer, most cases are diagnosed in the advanced stages of the disease. The curative potential of current standard treatment continues to be unsatisfactory, despite multimodal approaches involving surgery, chemotherapy and radiotherapy. Novel therapeutics including small molecules and monoclonal antibodies are being developed and have been partially introduced into clinical use in connection with neoplastic diseases such as chronic myeloid leukemia, non-Hodgkin's lymphoma and colorectal cancer. Thorough understanding of the changes in gene expression occurring during gastric carcinogenesis may help to develop targeted therapies and improve the treatment of this disease. Novel molecular biology techniques have generated a wealth of data on up- and down-regulation, activation and inhibition of specific pathways in gastric cancer. Here, we provide an overview of the different aspects of aberrant gene expression patterns in gastric cancer.


Rhabdomyolysis: a manifestation of cyclobenzaprine toxicity.
A case of cyclobenzaprine (flexeril) overdose and the resultant rhabdomyolysis is presented. A review of the range of clinical toxicity, management of overdose is described. The similarity of cyclobenzaprine to the tricyclic antidepressant class is emphasized; this report attempts to disseminate related information on this commonly prescribed centrally acting muscle relaxant.


Vascular responses of isolated mesenteric resistance and basilar arteries from short- and long-term diabetic rats.
Vascular dysfunctions, e.g. alterations in the reactivity of blood vessels to neurotransmitters and hormones, are a well-established complication of diabetes mellitus. Whether these impairments are a consequence of direct postsynaptic deficits and/or indirect presynaptic deficits remains to be determined. To this end, we investigated the influence of the duration of diabetes on relaxation and contraction responses of isolated mesenteric resistance and equally-sized basilar arteries to postsynaptic activation by various vasoactive agents, using streptozotocin-induced diabetic rats and age-matched controls. Relaxation responses to vasodilator agents were studied in KCl-precontracted arteries. The duration of diabetes (4 or 40 weeks) did not affect the vasodilator responses to sodium nitroprusside or salbutamol in either artery. In mesenteric resistance vessels from short-term (4 weeks) and long-term (40 weeks) diabetic rats the vasoconstrictor responses to KCI, serotonin and vasopressin were the same as those in non-diabetic rats; however, the sensitivity (EC50) to noradrenaline was slightly but significantly enhanced after the long-term diabetic state. In contrast to the mesenteric arteries, noradrenaline did not cause contraction in basilar arteries taken from diabetic and control rats. Thus, there appear to be important differences in the reactivity to noradrenaline of the peripheral and cerebral vasculature. The basilar artery from short-term and long-term diabetic rats did not show different responsiveness to vasopressin whereas to serotonin a significant enhanced and decreased sensitivity (EC10 and EC50) was demonstrated in short-term and long-term diabetes, respectively. Our findings indicate that postsynaptic impairments do not play a major role in the alterations of vasoreactivity to vasodilators, noradrenaline or vasopressin seen in experimental diabetes. However, the duration of the diabetic state may have serious consequences for vasoreactivity of basilar arteries to serotonin and, therefore, warrants further investigations.


A review of 50 pregnant patients with kyphoscoliosis.
An analysis of the obstetric and medical complications in 50 pregnant kyphoscoliotic patients is presented.


[Testing of visual function by the evoked potential method before and after surgical treatment of optico-chiasmal arachnoiditis].
Dynamics of changes of visual evoked potentials recorded in patients with optico-chiasmatic arachnoiditis in response to a flash of light were revealed during restoration of visual function in the postoperative period. In improvement of visual functions no changes were found of evoked potentials recorded in a chess pattern in the immediate postoperative period.


Ciclopirox gel for seborrheic dermatitis of the scalp.
Seborrheic dermatitis is a common inflammatory skin disorder that usually occurs in patients with pre-existing seborrhea. The etiology of seborrheic dermatitis is uncertain. Typically, sites dense with sebaceous glands support growth of the lipophilic yeast Malassezia furfur. Ciclopirox (Loprox) gel is a hydroxypyridone, broad-spectrum antifungal agent proven effective against the yeast M. furfur. A multicenter, randomized, double-blind, vehicle controlled study of 178 subjects evaluated the efficacy of ciclopirox gel in treating seborrheic dermatitis of the scalp. One hundred and seventy-eight subjects were randomized to apply either ciclopirox gel 0.77% twice daily, or vehicle twice daily for 28 days. Subjects' signs and symptoms of severity (erythema, scaling, pruritus and burning) were rated on a scale of 0-3 (none to severe); for inclusion, a minimum score of 4, for the sum of the individual ratings was required. Efficacy evaluations were performed at baseline, days 4, 8, 15, 22, 29, and at end-point (final visit, up to day 33). The primary efficacy variable was clinical response assessed by a global improvement, based on a scale of 0-5 (100% clearance to flare of treatment area). Changes in signs/symptoms severity scores within the target lesion were also evaluated. Global evaluation scores demonstrated that significantly more ciclopirox-treated subjects achieved over 75% improvement compared with vehicle at days 22, 29, and endpoint (P < 0.01). Change-from-baseline mean score for total signs and symptoms was significantly greater in ciclopirox subjects compared with vehicle subjects at the same time points as above (P < 0.001), as well as day 15 (P < 0.01). Twenty-nine percent of subjects rated ciclopirox as having excellent cosmetic acceptability. There were only mild adverse events, with the most common being burning sensation in 13% of ciclopirox subjects and 9% of vehicle subjects. Ciclopirox gel is effective and safe in the treatment of seborrheic dermatitis of the scalp.


Use of signal-averaged electrocardiography for predicting inducible sustained monomorphic ventricular tachycardia in patients with bundle branch block with and without a history of syncope.
The aim of this study was to examine the utility of signal-averaged electrocardiography in relation to inducible sustained monomorphic ventricular tachycardia in patients with bundle branch block. One hundred fourteen patients with bundle branch block underwent signal-averaged electrocardiography in the time domain and programmed ventricular stimulation. Sustained monomorphic ventricular tachycardia was induced in 17 patients. The mean values of the three signal-averaged electrocardiographic variables analyzed differed significantly between the inducible and the noninducible group. The filtered QRS duration showed the most prominent difference between the two groups, and a filtered QRS duration > or = 155 msec had a sensitivity of approximately 80%, a specificity of 60%, and a total predictive value of 65%. In the subgroup of patients with syncope, a combination of these criteria with a history of coronary artery disease had a sensitivity of 100% and a specificity of 90%.


Synergistic enhancement of the phytostabilization of a semiarid mine tailing by a combination of organic amendment and native microorganisms (Funneliformis mosseae and Bacillus cereus).
The goal of this work was to evaluate the effects of fermented sugar beet residue and inoculation with a native arbuscular mycorrhizal (AM) fungus, Funneliformis mosseae (Nicol. and Gerd.) Gerd. and Trappe, or a native bacterium, Bacillus cereus Frankland & Frankland, alone or in combination, on the establishment of Lygeum spartum L. seedlings grown in a mine tailing under semiarid conditions. We conducted a field study to analyse root and shoot dry biomass, shoot nutrient contents, mycorrhization, plant nitrate reductase (NR) and acid phosphomonoesterase activities, soil enzyme activities and aggregate stability. Ten months after field transplanting, it was found that the three experimental factors had interacted synergistically with regard to shoot and root biomass, with increases of about 410% and 370%, respectively relative to plants in the untreated soil. The treatment combining all three factors increased the root content of all heavy metals, and the levels of nitrogen (N), phosphorus, potassium and NR activity in shoot tissues, whereas it decreased root acid phosphomonoesterase activity. Soil dehydrogenase, protease and β-glucosidase activities, total N content and aggregate stability were increased by the combined treatment. In conclusion, the combination of the organic amendment, the native AM fungus and the native bacterium can be regarded as a suitable tool for phytostabilization with L. spartum due to its ability to enhance the tolerance of plants to heavy metals, improve the plant nutritional status and increase the soil microbial function related to the C cycling.


Ischaemic heart disease-an hypothesis to integrate the role of insulin, fibre and sucrose.
The theory that a high dietary cholesterol and saturated fat intake has an aetiological role in coronary artery disease is inadequate. So are those theories based upon insulin, upon refined carbohydrate and upon dietary sucrose. An alternate hypothesis is presented. Central to it is prolonged hyperinsulin-aemia. This, acting synergistically with the changes in lipide metabolism secondary to the effects of dietary fibre and sucrose, is crucial to atherogenesis. There is abundant evidence for an association of insulin and vascular changes, both in vitro and in epidemiological studies. Laboratory and epidemiological evidence also exists for an effect of fibre and soluble carbohydrate on cholesterol synthesis and excretion, both as itself and as bile acid. A scheme is presented to demonstrate these complex inter-relationships and their role in vascular diseases.


Increased expression of 14-3-3β promotes tumor progression and predicts extrahepatic metastasis and worse survival in hepatocellular carcinoma.
14-3-3β is implicated in cell survival, proliferation, migration, and tumor growth; however, its clinical relevance in tumor progression and metastasis have never been elucidated. To evaluate the clinical significance of 14-3-3β, we analyzed the association of 14-3-3β expression and clinicopathologic characteristics in primary and subsequent metastatic tumors of hepatocellular carcinoma patients. 14-3-3β was expressed abundantly in 40 of 55 (70.7%) primary tumors. Increased 14-3-3β expression in primary tumors predicted a higher 5-year cumulative incidence of subsequent extrahepatic metastasis, and multivariate analysis revealed 14-3-3β overexpression was an independent risk factor for extrahepatic metastasis. Patients with increased 14-3-3β expression in primary tumors had worse 5-year overall survival rates, and 14-3-3β overexpression was an independent prognostic factor on Cox regression analysis. Furthermore, stably overexpressed 14-3-3β enhanced hepatocellular carcinoma cell migration and proliferation and increased anchorage-independent cell growth. In addition, in vivo study in a nude-mice model showed tumor formation significantly increased with 14-3-3β overexpression. In conclusion, this is the first report to show that increased 14-3-3β expression is associated with subsequent extrahepatic metastasis and worse survival rates, as well as cancer progression of hepatocellular carcinoma. Thus, 14-3-3β may be a novel prognostic biomarker and therapeutic target in hepatocellular carcinoma.


Reversal of pulmonary circulation.
The preliminary results and the technique of total reversal of the pulmonary circulation (RPC) are presented. Total RPC is technically feasible and not incompatible with life. It affords a new experimental model for in vivo study of pulmonary pathophysiology. The influence of this reversal on blood oxygenation, on pulmonary vascular resistance, and on established pulmonary hypertension, as well as its reaction to hypoxia and acidosis, needs further investigation. RPC may have clinical implications in essential pulmonary hypertension and congenital pulmonary vascular anomalies.


Cosegregation of X-linked retinitis pigmentosa and hemophilia A.
We examined a family pedigree in which retinitis pigmentosa and hemophilia A were inherited in an X-linked manner. Six female carriers were identified by electroretinography. Results of ophthalmoscopic examination were normal in two women, while four displayed marked variability in phenotypic expression. Six of seven males identified with retinitis pigmentosa had hemophilia A. One asymptomatic boy had a markedly abnormal electroretinogram despite normal ophthalmoscopic examination. Pedigree analysis showed a high recombination rate, which would be expected as these two genes are known to be at opposite arms of the X chromosome.


Catalytic asymmetric synthesis of allylic thiol derivatives.
The palladium(II) complex [(Rp,S)-COP-Cl]2 and its enantiomer catalyze the rearrangement of linear prochiral O-allyl carbamothioates under mild conditions to provide branched S-allyl carbamothioates in high yield and high enantiomeric purity.


Overdispersion of ant colonies: a test of hypotheses.
The nest locations of two ant species in the Colorado Desert are intraspecifically overdispersed. Intraspecific overdispersion has been thought to represent strong intraspecific competition. Here we consider this hypothesis along with three competing hypotheses: microhabitat selection by foundress queens, predation on foundress queens, and predation on established colonies. To test these hypotheses five types of data were collected: (1) the forager population sizes of Veromessor pergandei and Pogonomyrmex californicus, (2) the response of the territory use of V. pergandei to varying levels of food, (3) the encounter rates of conspecifics and other ant species to foundress queens artificially placed near and far from conspecific colonies, (4) predation on colonies as a function of colony spacing, and (5) the relationship between the plant microhabitat at the nest and colony spacing. The results show that established colonies have no apparent selectivity for a particular type of plant microhabitat nor do foundress queens show avoidance or attraction toward conspecifics. V. pergandei workers show only a slight ability to find V. pergandei queens that are artificially placed near their entrances. Certain spiders are the most common ant predators on our study area. Direct observations on spiders indicate that colonies with closer neighbors are not prone to a higher risk of predation. In addition, the estimates of the death rate of workers from a mark-recapture technique indicate that colonies with closer neighbors lose similar numbers of workers as compared to colonies with further neighbors. In favor of the competition hypothesis, the summed size of intraspecific nearest neighbor pairs are larger for colonies that are spaced further apart than those colonies that are spaced closer together. We also develop an index of foraging directionality for the column foraging species V. pergandei. Using this measure, we find that nearest neighbors tend to avoid foraging toward each other. The response of territory use to food levels was tested with experiments involving patches of cracked wheat. These experiments showed that patches away from nearest neighbors were found significantly sooner than patches toward nearest neighbors. The above five sets of data together suggest that resource competition and perhaps queen predation by established colonies account for the intraspecific spatial patterns of these species.


Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space. Part III: Giant cell formation on the implanted lens surface.
Among the cell components appearing on an implanted intraocular lens (IOL), the macrophage is the most active participant in the foreign-body response. The morphological stages of the macrophage in the response include not only an activated form and a flat epithelioid cell, but also a giant cell observed in the later stage of the response. The giant cells on the IOLs implanted in the rabbit eye and in the mouse peritoneal space were investigated by means of Wolter's implant cytology staining and scanning and transmission electron microscopic observation. Differences in the two biological environments as the site of IOL implantation are discussed.


Emergency contraception knowledge after a community education campaign.
This study evaluates the effectiveness of a community education campaign in the Boston community of Jamaica Plain conducted by the Massachusetts Emergency Contraception (EC) Network aimed at improving public knowledge of EC. Pre- and postintervention surveys of reproductive-age women were conducted to evaluate the effectiveness of the community education campaign. Knowledge of EC was compared before and after the intervention using surveys of community-based samples of women. One hundred eighty-eight and 290 women participated in the preintervention and postintervention surveys, respectively. Following the intervention, women were significantly more likely to have heard of EC (91% vs. 82%, p=.007), know the mechanism of action of EC (49% vs. 39%, p=.04), have discussed EC with a health care provider (38% vs. 25%, p=.003) and have received an advance prescription for EC (22% vs. 12%, p=.004), as well as were more likely to use EC in the future if needed (79% vs. 63%, p=.0002). This grassroots-based community education campaign on EC was effective in improving EC knowledge in this Boston community.


How effective are self-management interventions in promoting health-related quality of life in people after primary treatment for breast cancer? A critical evidence synthesis.
Self-management interventions (SMIs) are designed to empower people living beyond breast cancer and help them adjust to a new normal. This structured review aimed to critically appraise and synthesise up-to-date evidence on the effectiveness of SMIs to promote health-related quality of life (HRQoL) in people with breast cancer in the post-treatment period. According to PRISMA statement guidelines, MEDLINE, EMBASE and CINAHL were searched for peer-reviewed publications of randomised controlled trials of SMIs. Pre-specified selection criteria were applied to all retrieved records. Methodological quality and risk of bias were evaluated by using the Caldwell framework and Cochrane Collaboration Risk of Bias tool, respectively. Findings were integrated into a narrative critical evidence synthesis. Nine eligible trials were identified that tested nine SMIs. Five SMIs were based on cognitive behaviour therapy (CBT). Eight SMIs targeted recipients' decision-making and taking-action skills. Across trials, gains in one to four domains of HRQoL were reported. SMIs predominantly promoted recipients' physical and functional well-being, regardless of methodological quality or self-management skills applied, but effect sizes were consistently small. SMIs were mainly prescribed for 12 weeks, but optimal dosage cannot be confirmed currently. SMIs informed by CBT and/or offered through recipient education were marginally more effective. Evidence derived from moderate-to-good quality trials. SMIs are potentially effective after primary treatment for breast cancer, although effect sizes are small and inconsistent across HRQoL domains. More rigorous development and testing is required, while co-production from the early development stages or at the refinement phase is recommended.


Klinefelter's syndrome and acute leukemia.
Klinefelter's syndrome is associated with an increased risk of certain types of cancer. A small number of reports have documented the occurrence of acute leukemia in these patients. Our review of 1200 consecutive patients investigated cytogenetically for actual or suspected hematologic malignancy revealed only one patient with acute leukemia and the 47,XXY syndrome. This finding suggests that the risk of acute leukemia in Klinefelter's patients is no greater than that of the general population.


Biochemical ecology of the forest tent caterpillar: responses to dietary protein and phenolic glycosides.
Interactions between quaking aspen (Populus tremuloides) and the forest tent caterpillar (Malacosoma disstria) are likely to be influenced by leaf protein and phenolic glycoside levels, and insect detoxication activity. We investigated the direct and interactive effects of dietary protein and phenolic glycosides on larval performance and midgut enzyme activity of forest tent caterpillars. We conducted bioassays with six artificial diets, using both first and fourth stadium larvae. Four of the diets comprised a 2×2 factorial design-two levels of protein, each with and without phenolic glycosides. Additionally, we assayed high protein diets containing S,S,S-tributylphosphorotrithioate (DEF, an esterase inhibitor) and DEF plus phenolic glycosides. Enzyme solutions were prepared from midguts of sixth instars and assayed for β-glucosidase, esterase and glutathione transferase activities. First instar mortality and development times were higher for larvae on diets low in protein or containing phenolic glycosides. Effects of phenolic glycosides were especially pronounced at low protein levels and when administered with DEF. Fourth instar development times were prolonged, and growth rates reduced, in response to consumption of low protein diets. Effects of phenolic glycosides on growth were less pronounced, although the effect for larvae on the low protein diet was nearly significant. Activity of each of the enzyme systems was reduced in larvae reared on low protein diets, and esterase activity was induced in larvae fed phenolic glycosides. Our results suggest that larval performance may be strongly affected by levels of protein and phenolic glycosides commonly occurring in aspen foliage, and that these factors may play a role in differential defoliation of aspen by forest tent caterpillars.


Derivation of sensory neurons and neural crest stem cells from human neural progenitor hNP1.
Although sensory neurons constitute a critical component for the proper function of the nervous system, the in vitro differentiation of functional sensory neurons from human stem cells has not yet been reported. This study presents the differentiation of sensory neurons (SNs) from a human neural progenitor cell line, hNP1, and their functional maturation in a defined, in vitro culture system without murine cell feeder layers. The SNs were characterized by immunocytochemistry and their functional maturation was evaluated by electrophysiology. Neural crest (NC) precursors, as one of the cellular derivatives in the differentiation culture, were isolated, propagated, and tested for their ability to generate sensory neurons. The hSC-derived SNs, as well as the NC precursors provide valuable tools for developing in vitro functional systems that model sensory neuron-related neural circuits and for designing therapeutic models for related diseases.


Preferential outcrossing in the complex species Persoonia mollis R. Br. (Proteaceae).
The breeding system of the extremely diverse species Persoonia mollis (Proteaceae) was characterized to, firstly, assess its importance as a mechanism promoting diversity and, secondly, to investigate the mode of control over selective fruit abortion. Fruit quantity and quality was assessed following self-and outcross-pollination manipulations. Twenty percent of outcrossed flowers set fruit, compared to only 1% of flowers fertilized with self-pollen. Fruits produced by self-fertilization were 72% of the weight of cross-fertilized fruits. Fruits produced by self-fertilization were significantly fewer in number and lighter than fruits following natural pollination of unmanipulated flowers (17% fruit set), but outcrossed and naturally pollinated fruits were equivalent. Flower to fruit demography suggested that a post-zygotic mechanism may be preferentially selecting the most vigorous zygote genotypes, as ovary abscission occurs mostly between 4 and 30 weeks after pollination, regardless of pollen source. Self-pollen tube growth was found to be inhibited within the styly, while pollen tubes were found in the ovary for 50% of all outcrossed flowers. These data suggest that a pre-zygotic "pseudo" self-incompatibility mechanism is the cause of low fruit set following self-pollination. The breeding system of P. mollis was found to promote outbreeding, with an emphasis on flexibility and post-zygotic choice following pre-zygotic "pseudo" self-incompatibility.


Primary and secondary synovial chondrometaplasia: histopathologic and clinicoradiologic differences.
One hundred thirty-six cases diagnosed clinically as either synovial chondrometaplasia or osteocartilaginous loose bodies were reviewed. On the basis of the histopathologic peculiarities, the cases were grouped into two distinct categories, primary and secondary synovial chondrometaplasia, comprising 10 and 126 cases, respectively. In each group there was synovial chondrometaplasia but the histologic patterns were dissimilar. In cases of secondary synovial chondrometaplasia the initiating factors were usually obvious and the lesions were nonaggressive. Primary synovial chondrometaplasia, on the other hand, was aggressive and was associated with a high incidence of recurrence.


Convergent enantioselective synthesis of vinigrol, an architecturally novel diterpenoid with potent platelet aggregation inhibitory and antihypertensive properties. 1. Application of anionic sigmatropy to construction of the octalin substructure.
The coupling of building blocks 15 and 36e in the presence of MgBr(2).OEt(2) at 0 degrees C proceeds with an exo stereoselectivity (3.2:1) considerably more advantageous for the acquisition of carbinol 37e than in the absence of the additive (exo/endo = 1:5.7). The pivotal transformation that sets all of the relevant stereocenters of the cis-octalin 55 is the oxyanionic-accelerated [3,3]-sigmatropic rearrangement of 37e. A salient feature is the structurally enforced adoption of a boatlike transition state that serves to properly set four vicinal methine hydrogens in an all-cis arrangement. The ensuing conversion of 55 into iodo sulfone 62 has permitted X-ray crystallographic confirmation of all absolute stereochemical assignments since the isopropyl substituent was initially installed enantioselectively via the Evans oxazolidinone protocol. No intramolecular anionic cyclization of 62 to generate the tricyclic framework was seen. This absence of reactivity is attributed to conformational factors that inhibit attainment of the proper S(N)2 reaction trajectory.


Starting dose selection and dose escalation for oncology small molecule first-in-patient trials: learnings from a survey of FDA-approved drugs.
The ideal starting dose for an oncology first-in-patient (FIP) trial should be low enough to be safe but not too far removed from therapeutically relevant doses. A low starting dose combined with small dose increments could lead to a lengthy dose escalation and could expose patients unnecessarily to sub-therapeutic dosing. In the current analyses, we reviewed 59 approved small molecule oncology drugs (SMOD) with the overarching goals to assess the current approaches of FIP starting dose selection and dose escalation, and to identify potential opportunities for improving trial efficiency and minimizing number of patients receiving sub-therapeutic dose levels. Of 59 SMODs, the majority (~ 66%) were kinase inhibitors and ~ 73% were approved for solid tumor indications. Most of the trials used a 3 + 3 design for dose escalation and had a median (range) of 4 cohorts (0-11) to reach MTD from the starting dose. The maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) to starting dose ratio was highly variable with a median (range) of 8 (0.25-125). About 71% of the FIP trials had < 6 dose escalation steps to reach MTD or RP2D (with 15% ≤ 2 dose escalations), but the remaining 29% of trials had ≥ 6 dose escalation steps to reach MTD or RP2D suggesting that there is still room for increasing efficiency by reducing the number of dose escalation steps, reducing the variability in MTD to starting dose ratio, and consequently reducing significant number of patients exposed at sub-therapeutic doses in the dose escalation phase of FIP study.


Myocarditis and dilated cardiomyopathy in athletes: diagnosis, management, and recommendations for sport activity.
This article focuses on uncommon heart diseases associated with an increased risk for sudden death during exercise, namely, myocarditis and dilated cardiomyopathy.


Efficacy of an acellular pertussis vaccine in Japan.
To assess the efficacy of an acellular pertussis vaccine that has been used in Japan since 1981, 283 patients with pertussis were selected among patients with suspected pertussis seen at hospitals located around the Tokyo Metropolitan area from 1981 to 1983. The survey of secondary cases in household contacts showed that attack rates in children 0 to 6 years of age were 73.1% in unimmunized children, 15.0% in those fully immunized by whole-cell vaccines, and 15.4% in those given acellular vaccines. The efficacy of Japanese acellular pertussis vaccines was 79% and was not different from that of whole cell vaccines.


Comparison of whole-body vertical stiffness and leg stiffness during single-leg hopping in place in children and adults.
In the hopping literature, whole-body vertical stiffness and leg stiffness are used interchangeably, due to most of the movement occurring in the vertical direction. However, there is some anterior/posterior movement of the center of mass and displacements of the foot during hopping in place in both children and adults. Further it is not understood if leg stiffness show a similar pattern as whole-body vertical stiffness when increasing hopping frequency. The purpose of this study was to test if whole-body vertical stiffness and leg stiffness are different during single-leg hopping in-place in children and adults, across a range of frequencies. Seventeen children aged 5-11years and 16 young adults participated in this study. The subjects hopped at their preferred frequency as well as 20% below, 20% above and 40% above preferred frequency. Our results demonstrate that both whole-body vertical stiffness and leg stiffness increase when increasing hopping frequency for children and adults. However, whole-body vertical stiffness consistently overestimates leg stiffness due to a similar peak force but a greater leg length change compared to vertical COM displacement. This suggests a considerable horizontal COM movement from landing to mid-stance during hopping. Children aged 5-11years old showed lower absolute values but higher normalized values of two stiffness measures than adults. This suggests somewhat adult-like stiffness control in children, but a reduced ability to manipulate the horizontal movement during single-leg hopping in place when compared to adults.


Kinetics of left ventricular rotation during exercise and its relation to exercise tolerance in atrial fibrillation: assessment by two-dimensional speckle tracking echocardiography.
Left ventricular (LV) rotation plays an important role in cardiac function both at rest and during exercise in sinus rhythm. The kinetics of rotation during exercise and the relation between exercise tolerance and rotation-related parameters in patients with atrial fibrillation (AF) are unknown. Twenty-nine patients (age 62 ± 13 years, 6 females) with AF and preserved LV ejection fraction (LVEF) were studied using two-dimensional speckle tracking echocardiography at rest and during exercise with a supine bicycle ergometer (20 W, 10 min). We measured the systolic rotation (Rot) and the peak rotation rate in systole and early diastole (eRotR) at the apical and basal levels of the LV. All patients underwent cardiopulmonary exercise testing to obtain their percent achieved of the predicted peak oxygen consumption (% peak VO2) value. During exercise, apical Rot-related indices were significantly increased only in the preserved % peak VO2 group. In contrast, E/e' was significantly elevated only in the reduced % peak VO2 group. Multivariable stepwise regression analysis showed that apical ΔRot was independently associated with % peak VO2 (β = 0.72; p < 0.01). Apical ΔeRotR, which could not be selected as an independent predictor of % peak VO2, had a good linear correlation with apical ΔRot (r = 0.81, p < 0.01). The augmentation of apical rotation in response to exercise may coincide with an increase of the apical derotation rate, and apical rotation reserve may reflect exercise tolerance in patients with AF and preserved LVEF.


Parental rearing behaviour and personality characteristics of depressed patients.
Within the framework of a large and ongoing study of depression in its biological, clinical, psychological and social aspects, 141 patients of both sexes in the age range 21 to 65 years participated in a study of parental rearing practices and personality characteristics. The perceived parental rearing behaviour was assessed by means of a specially constructed inventory (EMBU), and the personality characteristics by means of a Swedish personality inventory, the KSP, which had previously been shown to measure relatively stable personality characteristics. Several important correlations emerged between parental rearing practices and personality traits. In particular, power assertive practices and psychological types of discipline (shaming, guilt-engendering) showed significant correlations with aspects of aggression and significant negative correlations with socialization. There was a good agreement between male and female patients in the judgement of the rearing behaviour of their fathers. However, female patients scored their mother as more abusive, whereas male patients scored them as more over-protective. On the whole, the rearing practices of the mothers were judged more negatively than those of the fathers. The findings of this study appear to be consistent with earlier results reported by other authors.


Prognostic significance of morphometric endomyocardial biopsy analysis in patients with idiopathic dilated cardiomyopathy.
To date, considerable controversy exists on the prognostic significance of morphometric endomyocardial biopsy findings in patients with idiopathic dilated cardiomyopathy (IDC). Quantitative analyses of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters of left ventricular endomyocardial biopsy specimens were performed in 124 patients with IDC. During 51 +/- 22 months follow-up after left ventricular endomyocardial biopsy, major arrhythmic events, defined as sustained ventricular tachycardia (VT), ventricular fibrillation (VF), or sudden cardiac death, were observed in 24 patients (19%). Death from any cause or heart transplant was observed in 39 patients (31%). The amount of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters determined from left ventricular endomyocardial biopsy specimens did not differ significantly between patients with and patients without major arrhythmic events or between patients with and patients without transplant-free survival during follow-up. Quantitative analysis of the amount of interstitial structured tissue, myofibril volume fraction, and myocytic fiber diameters in left ventricular endomyocardial biopsy specimens does not appear to be useful for predicting arrhythmic events and transplant-free survival in IDC.


Transfection in Primary Cultured Neuronal Cells.
Transfection allows the introduction of foreign nucleic acid into eukaryotic cells. It is an important tool in understanding the roles of NMDARs in neurons. Here, we describe using lipofection-mediated transfection to introduce cDNA encoding NMDAR subunits into postmitotic rodent primary cortical neurons maintained in culture.


Posterior chamber intraocular lens implantation during pars plana lensectomy and vitrectomy for diabetic complications.
Ten eyes had posterior chamber lenses implanted in the ciliary sulcus in front of the anterior lens capsule during diabetic pars plana lensectomy and vitrectomy. Six months later, nine eyes had improved vision and one had the same vision as compared with preoperative acuity levels. Two eyes had 0.5 and eight eyes had 0.1 or better acuity. None of the eyes developed iris or angle neovascularization or glaucoma, and all ten eyes had clear vitreous cavities with attached maculas. The posterior chamber lenses were well tolerated and provided good visual rehabilitation.


mRNA delivery in cancer immunotherapy.
Messenger RNA (mRNA) has drawn much attention in the medical field. Through various treatment approaches including protein replacement therapies, gene editing, and cell engineering, mRNA is becoming a potential therapeutic strategy for cancers. However, delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular uptake. Therefore, in addition to mRNA modification, efforts have been devoted to developing nanoparticles for mRNA delivery. In this review, we introduce four categories of nanoparticle platform systems: lipid, polymer, lipid-polymer hybrid, and protein/peptide-mediated nanoparticles, together with their roles in facilitating mRNA-based cancer immunotherapies. We also highlight promising treatment regimens and their clinical translation.


Social networks and job quality in Mexico: 2005-2019.
This investigation analyzes labor implications of employment procurement through friends and family on wages, workers' benefits and job longevity in comparison to other job search methods in Mexico during 2005-2019. Various econometric models are performed. For salary, fixed effects by city and year will be estimated through Pooled Ordinary Least Squares (OLS). Second, it is analyzed if jobs obtained through friends and family are more likely to provide benefits equal to or greater than those required by law, for this, a logistic model and an ordered logistic model are employed with fixed effects; and finally, for the duration of employment we use a parametric survival model. The results indicate that employment procured through family and friends result in higher salaries and longer work durations but less work benefits.


Stimulation of cell growth in the U-937 human myeloid cell line by honey royal jelly protein.
Royal jelly was fractionated by ion-exchange chromatography and a protein (DIII protein) that had growth stimulating activity to the U-937 human myeloid cell line was obtained. The molecular weight of the DIII protein was 58 kDa on SDS-PAGE. The growth stimulating activity of the DIII protein was shown to be relatively heat and pH stable.


Randomized controlled comparison of two cognitive behavioral therapies for obese children: mother versus mother-child cognitive behavioral therapy.
Parent-child treatments have been shown to be superior to child-focused treatments of childhood obesity. Yet until now, the comparative effectiveness of parent-only and parent-child approaches has been little studied. Fifty-six obese children and their families were randomly assigned to a 16-session cognitive behavioral therapy (CBT) for the parents only or for a combined treatment of parents and children. Children's percent overweight, the body mass index of their mothers, and behavioral and psychological problems of children and mothers were assessed. Both treatments reduced children's percent overweight significantly and equally by 6-month follow-up. Also both treatments provided similar results in reducing general behavior problems (externalizing and internalizing behavior problems), global and social anxiety, and depression. Our results point to a comparable efficacy of the two treatments. Further, psychological well-being of both mothers and children can be improved in a CBT for obese children and their parents. Future studies should focus on finding ways to improve the adherence of families to long-term treatment of obesity in childhood.


The effect of energy losses in alpha-particle sources on the shape of peaks in spectra obtained with wide-angle geometry.
It has been shown that two main effects contribute to the tailing in the shapes of alpha-peaks measured with silicon detectors: the ionization loss in the source and the response of the detector. We studied the relative influence of both factors in measurements with small source-to-detector distances. The computer simulation code 'the stopping and range of ions in matter' has been used to obtain the energy spectra of a 226Ra source as a function of the source thickness. Results of the simulation are compared with experimental measurements.


Single Cell RNA Sequencing of Human Milk-Derived Cells Reveals Sub-Populations of Mammary Epithelial Cells with Molecular Signatures of Progenitor and Mature States: a Novel, Non-invasive Framework for Investigating Human Lactation Physiology.
Cells in human milk are an untapped source, as potential "liquid breast biopsies", of material for investigating lactation physiology in a non-invasive manner. We used single cell RNA sequencing (scRNA-seq) to identify milk-derived mammary epithelial cells (MECs) and their transcriptional signatures in women with diet-controlled gestational diabetes (GDM) with normal lactation. Methodology is described for coordinating milk collections with single cell capture and library preparation via cryopreservation, in addition to scRNA-seq data processing and analyses of MEC transcriptional signatures. We comprehensively characterized 3740 cells from milk samples from two mothers at two weeks postpartum. Most cells (>90%) were luminal MECs (luMECs) expressing lactalbumin alpha and casein beta and positive for keratin 8 and keratin 18. Few cells were keratin 14+ basal MECs and a small immune cell population was present (<10%). Analysis of differential gene expression among clusters identified six potentially distinct luMEC subpopulation signatures, suggesting the potential for subtle functional differences among luMECs, and included one cluster that was positive for both progenitor markers and mature milk transcripts. No expression of pluripotency markers POU class 5 homeobox 1 (POU5F1, encoding OCT4) SRY-box transcription factor 2 (SOX2) or nanog homeobox (NANOG), was observed. These observations were supported by flow cytometric analysis of MECs from mature milk samples from three women with diet-controlled GDM (2-8 mo postpartum), indicating a negligible basal/stem cell population (epithelial cell adhesion molecule (EPCAM)-/integrin subunit alpha 6 (CD49f)+, 0.07%) and a small progenitor population (EPCAM+/CD49f+, 1.1%). We provide a computational framework for others and future studies, as well as report the first milk-derived cells to be analyzed by scRNA-seq. We discuss the clinical potential and current limitations of using milk-derived cells as material for characterizing human mammary physiology.


An innovative accelerated carbonation process for treatment of incineration bottom ash and biogas upgrading.
Incineration is the main technology used for the management of municipal solid waste, in parallel to various recycling programs. However, incineration should not be considered as the final step for waste management as the ash still needs to be treated and disposed properly. In this work, an innovative accelerated carbonation of incineration bottom ash (IBA) using simulated biogas composition from anaerobic digestion processes (a mixture of CH4 and CO2) has been applied to lower the leaching of heavy metals from the carbonated IBA and its associated toxicity. Various temperatures and reaction times were explored for carbonation optimization and it was found that the carbonation at 25 °C for 8 h was the optimal reaction condition by taking into account the degree of carbonation and time constraint. The mineral content, functional groups, thermal stability, leaching patterns and ecotoxicity of both raw IBA and carbonated IBA were tested. It was found that carbonated IBA leached out less heavy metals than the raw IBA due to the locking of heavy metals in the calcite matrix. Cost-benefit analysis was also conducted on the industrial-scale process with a capacity of processing 10 tons of IBA per day. The results indicated that the proposed process had great economic potential.


Hybrid Pyridine-Pyridone Foldamer Channels as M2-Like Artificial Proton Channels.
Currently, completely abiotic channel systems that concurrently reproduce the high selectivity and high permeation rate of natural protein channels are rare. Here, we provide one such biomimetic channel system, i.e., a novel family of helically folded hybrid amide foldamers that can serve as powerful artificial proton channels to mimic key transport features of the exceptionally selective Matrix-2 (M2) proton channels. Possessing an angstrom-scale tubular pore 3 Å in diameter, these low water permeability artificial channels transport protons at a rate 1.22 and 11 times as fast as gramicidin A and M2 channels, respectively, with exceptionally high selectivity factors of 167.6, 122.7, and 81.5 over Cl- , Na+ , and K+ ions. Based on the experimental and computational findings, we propose a novel proton transport mechanism where a proton may create a channel-spanning water chain from two or more short water chains to facilitate its own transmembrane flux via the Grotthuss mechanism.


The learning curve revisited: stapedotomy.
To determine whether the outcome of stapedotomy changes with experience. Retrospective case review of an academic otologic practice of a fellowship-trained otologist that consisted of 50 consecutive patients who underwent primary stapedotomy. The main outcome measures were preoperative and postoperative audiograms for both the operated ear and the opposite ear (control). There were no major complications or loss of hearing among the 50 patients. Minor complications included 1 middle ear infection, 2 torn flaps, and 1 tympanic membrane perforation. One patient had worse conductive hearing loss after surgery. The hearing of 2 patients was unchanged. Hearing for the entire group improved (P > 0.001) from a speech reception threshold of 55 dB (SD, 17 dB) to 30 dB (SD, 19 dB). Complete closure of the air-bone gap was achieved in 20% of the first 10 patients and 30% of the last 10 patients. The results of stapedotomy improve with experience, although the learning curve seems less steep than has been reported for total or near-total footplate removal. Stapedotomy can be successfully performed early in surgical experience, but the learning curve should be acknowledged and discussed with the patient.


Exogenous ketosis increases circulating dopamine concentration and maintains mental alertness in ultra-endurance exercise.
Exogenous ketosis can improve psychocognitive functioning during exercise as well as stimulate postexercise muscular recovery. Therefore, we hypothesized that ketone ester (KE) supplementation can counteract the decline in psychocognitive functioning during ultra-endurance exercise and stimulate muscular recovery. Eighteen recreational runners participated in a full 100 km trail run (RUN, n = 8), or ran to premature exhaustion (80 km: n = 6; 60 km: n = 4). Before (25 g), during (25 g·h-1), and after (5 × 25 g in 24 h) RUN they received ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE, n = 9) supplements or a noncaloric placebo (CON, n = 9). Blood samples and muscle biopsies were taken, and mental alertness was assessed by a psychocognitive test battery at different times before, during, and up to 36 h after RUN. Compared with CON (<0.3 mM), in KE blood d-β-hydroxybutyrate concentration was consistently elevated to ∼2-3 mM during RUN. In CON, RUN increased visual reaction times from 353 ± 53 to 419 ± 54 ms, and movement execution times from 174 ± 47 to 245 ± 64 ms. But this effect was fully negated by KE (P < 0.05). Plasma dopamine concentrations doubled in KE during RUN but remained stable in CON, resulting in higher concentrations after RUN in KE (4.1 ± 1.7 nM) than in CON (2.4 ± 0.8 nM, P = 0.048). KE also inhibited muscular infiltration of macrophages and suppressed AMPK phosphorylation status until 36-h postexercise (P < 0.05 KE vs. CON). In conclusion, KE increases circulating dopamine concentration and improves mental alertness, as well as improves postexercise muscular inflammation in ultra-endurance exercise.NEW & NOTEWORTHY Oral ketone ester ingestion elevates circulating dopamine concentration during ultra-endurance exercise. This is associated with improved mental alertness. Furthermore, ketone ester intake inhibits postexercise skeletal muscle macrophage infiltration, and counteracts the increase in AMPK phosphorylation after exercise, which indicates improved muscular energy status.


Molecular dynamics imaging in micropatterned living cells.
Micropatterning approaches using self-assembled monolayers of alkyl thiols on gold are not optimal for important imaging modalities in cell biology because of absorption of light and scattering of electrons by the gold layer. We report here an anisotropic solid microetching (ASOMIC) procedure that overcomes these limitations. The method allows molecular dynamics imaging by wide-field and total internal reflection fluorescence (TIRF) microscopy of living mammalian cells and correlative platinum replica electron microscopy.


Efficacy and safety of G-CSF, low-dose cytarabine and aclarubicin in combination with l-asparaginase, prednisone in the treatment of refractory or relapsed acute lymphoblastic leukemia.
Acute lymphoblastic leukemia (ALL) patients who fail to acquire complete remission (CR) or who relapse after initial response have poor prognosis. At present there is no consensus as to the standard salvage therapy for these patients. In this study, we retrospectively evaluate safety and efficacy of a salvage regimen (CAGLP) consisting of G-CSF, low-dose cytarabine, aclarubicin, l-asparaginase and prednisone. Thirty-six patients were included with primary refractory (n=13) or relapse (n=23). The overall response rate (ORR) and CR rate were 86.1% and 63.9%, respectively. With a median follow-up of 34 months, the probability of overall survival (OS) at 2 years was 30%±10% and the disease-free survival (DFS) rate was 15%±8%. Treatment-related mortality was 5.6%. Our preliminary results indicated that CAGLP was feasible, safe and effective as a salvage reinduction chemotherapy for primary refractory and relapsed ALL patients.


Discrepancies between histological and physical methods for trace element mapping in the rat brain.
This paper contains a comparison between four experimental methods for the detection of trace metals in biological tissues, e.g. autoradiography, dithizone-, Timm-staining and microPIXE (Particle Induced X-ray Emission). As research object the hippocampus of the rat was chosen and mainly the Zn-distribution in the fascia dentata has been examined. The comparison was judged on four criteria: spatial resolution, specificity, quantification and influence of the protein binding of the metal on the outcome of each method. Some additional Timm and microPIXE experiments have been performed to compare the metal concentrations for both normal and Zn-deficient rats. The Zn/Cu ratio for both kinds of rats were calculated and some striking differences in the concentrations were obtained. The Zn/Cu ratio for a normal rat was found to be about 40% higher than for a deficient one.


Multicentre analysis of 178,992 type 2 diabetes patients revealed better metabolic control despite higher rates of hypertension, stroke, dementia and repeated inpatient care in patients with comorbid Parkinson's disease.
Especially in older people, physicians are faced with the coexistence of type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). Therefore, this research aimed to compare diabetes endpoints between T2DM with and without PD. Based on the standardized, multicenter, prospective DPV database, 178,992 T2DM patients (≥40 years) were analyzed. 1579 were diagnosed with PD and/or received specific treatment. Hierarchical multivariable regression models were used for group comparisons; adjusted estimates based on observed marginal frequencies were calculated. PD patients were significantly older (77.9 vs. 70.0 years; p < 0.0001) and had a longer diabetes duration (10.3 vs. 8.4 years; p < 0.0001). In young PD patients (<50 years), percentage of females was significantly higher compared to age-matched T2DM patients without PD or people of the German population (66.7 vs. 38.1 vs. 49.0%; p < 0.0001, p < 0.02). After demographic adjustment, T2DM patients with PD showed a significantly lower HbA1c (58.0 vs. 60.3 mmol/mol; p < 0.0001), OAD/GLP-1 treatment (41.9 vs. 45.9%; p < 0.01) and frequency of dyslipidemia (62.0 vs. 64.5%; p < 0.05). In contrast, rates of insulin therapy (57.8 vs. 54.8%; p < 0.05), hypertension (73.3 vs. 68.6%; p < 0.001), antihypertensive medication (60.4 vs. 56.1%; p < 0.01), stroke (12.0 vs. 7.3%; p < 0.0001), dementia (9.2 vs. 2.6%; p < 0.0001) and repeated inpatient care (15.7 vs. 12.0%; p < 0.0001) were significantly higher and duration of hospital stay (6.2 vs. 4.7 days; p < 0.0001) was significantly longer in T2DM with PD. Clear demographic and clinical differences were observed between T2DM with and without PD. In PD patients, metabolic control is better, potentially due to more intensive medical care.


Performance characteristics of a microsphere immunoassay using recombinant HCV proteins as a confirmatory assay for the detection of antibodies to the hepatitis C virus.
The detection of antibody to hepatitis C virus (HCV) is an important assay for the identification of individuals infected with this virus. However, the confirmation of antibody positivity remains problematic. Currently none of the screening or confirmatory assays provide quantitation of the antibodies present. A microsphere assay was designed to provide improved confirmation. Microspheres of 3.6 mum in diameter coated with NeutraAvidin were used to capture biotinylated HCV recombinant proteins. A phycoerythrin goat anti-human immunoglobulin G (IgG) was used to detect specific antibody captured to the microsphere. A human IgG calibrator was designed that was internal to each sample in the microsphere assay. Detection of HCV-specific antibody using these microspheres was straightforward in most samples, with the lower detection limit set at 0.01 microg equivalents of human IgG per milliliter. In antibody-positive samples, the HCV antibody levels ranged from 0.09 to 55 microg equivalents of IgG per milliliter. Forty-nine of the 54 samples (91%) previously identified as having an indeterminate serologic pattern were negative in the microsphere assay. The microspheres and biotinylated HCV proteins were stable for longer than 8 months when stored at 2 degrees C to 8 degrees C and coating of the microspheres was reproducible with an interassay coefficient of variation less than 10%. Avidin-coated microspheres provide an easy solid support on which to design an assay provided the capture reagent being used can be biotinylated effectively. Confirmation of antibody to HCV can be performed using this assay format.