Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer.
New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR-132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 μg/day) or JV-1-38 (20 μg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1α, metalloproteinases (MMPs) -2 and -9, β-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1α expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated β-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer.


Cat hindlimb motoneurons during locomotion. I. Destination, axonal conduction velocity, and recruitment threshold.
Fine flexible wire microelectrodes chronically implanted in the fifth lumbar ventral root (L5 VR) of 17 cats rendered stable records of the natural discharge patterns of 164 individual axons during locomotion on a treadmill. Fifty-one out of 164 axons were identified as motoneurons projecting to the anterior thigh muscle group. For these axons, the centrifugal propagation of action potentials was demonstrated by the technique of spike-triggered averaging using signals recorded from cuff electrodes implanted around the femoral nerve. The axonal conduction velocity was measured from the femoral nerve cuff records. For 43/51 motoneurons, the corresponding target muscle was identified by spike-triggered averaging of signals recorded from bipolar EMG electrodes implanted in each of the anterior thigh muscles: vastus intermedius, medialis and lateralis, sartorius anterior and medialis, and rectus femoris. For 32/51 motoneurons, the recruitment threshold during locomotion was determined from the mean value of the rectified digitally smoothed EMG of the target muscle measured at the time when the motoneuron fired its first spike for each step. The recruitment threshold of every motoneuron was relatively constant for a given speed of walking, but for some units there were small systematic variations as a function of treadmill speed (range: 0.1-1.3 m/s). Recruitment thresholds were standardized with respect to the mean value of peak EMG activity of the target muscle during 16 s of walking at 0.5 m/s. For 28/51 motoneurons recorded in nine cats, recruitment thresholds (range: 3-93% of peak target muscle EMG) were linearly correlated (r = 0.51, P less than 0.02) to axonal conduction velocities (range: 57-117 m/s). In addition, for seven recorded pairs of motoneurons that projected to the same muscle in the same cat, the recruitment thresholds were ordered by relative conduction velocities. Taken together, these results are consistent with the notion that, in normal cat locomotion up to a medium trot, anterior thigh motoneurons are progressively recruited in an orderly fashion.


Comparing the Sensitivities of Measures of Adherence to Antihypertensive Drugs Using Korean National Health Insurance Claims Data.
Numerous studies have utilized various forms of adherence measures. However, methods for measuring adherence are inconsistent. Moreover, few studies are available that have compared sensitivities of the effects of several criteria on medication adherence. This study aims to compare measures of adherence using varied analytical decisions. We included three measures for adherence: proportion of days covered with one or more medications (PDCwith≥1), duration weighted mean PDC (PDCwm), and daily polypharmacy possession ratio (DPPR). We compared the sensitivities of the measures by changing parameters in the Korean nationwide claims database. First, we used PDCwith≥1 as our base model. Then, we divided an adherence measure algorithm into three categories: (1) definition of data cleaning, (2) inclusion criteria and observation period, and (3) calculation methods of medication adherence. The categories included eight decision nodes that incorporated 25 alternative options. Finally, we assessed the medication adherence for the base-case with commonly used values and then varied to measure with each alternative option. The base-case included 14,288 beneficiaries with antihypertensives. Among eight decisions, both handling an end-date-of-study and overlaps had the strongest impacts on measuring PDCwith≥1, PDCwm, and DPPR, with small differences in sample size. Instead of the estimates of adherence from PDCwm, those of PDCwith≥1 and DPPR were similar. Furthermore, a tendency toward a higher medication adherence was observed with a smaller study population. The decisions regarding identifying an end-date-of-study and overlaps showed meaningful impacts of all three measures including PDCwith≥1, PDCwm, and DPPR on measuring medication adherence.


Dynamically Modulated Mask Sparse Tracking.
Visual tracking is a critical task in many computer vision applications such as surveillance and robotics. However, although the robustness to local corruptions has been improved, prevailing trackers are still sensitive to large scale corruptions, such as occlusions and illumination variations. In this paper, we propose a novel robust object tracking technique depends on subspace learning-based appearance model. Our contributions are twofold. First, mask templates produced by frame difference are introduced into our template dictionary. Since the mask templates contain abundant structure information of corruptions, the model could encode information about the corruptions on the object more efficiently. Meanwhile, the robustness of the tracker is further enhanced by adopting system dynamic, which considers the moving tendency of the object. Second, we provide the theoretic guarantee that by adapting the modulated template dictionary system, our new sparse model can be solved by the accelerated proximal gradient algorithm as efficient as in traditional sparse tracking methods. Extensive experimental evaluations demonstrate that our method significantly outperforms 21 other cutting-edge algorithms in both speed and tracking accuracy, especially when there are challenges such as pose variation, occlusion, and illumination changes.


Advancements and Future Outlook of PET/CT-Guided Interventions.
Advancements in minimally invasive technology, coupled with imaging breakthroughs, have empowered the field of interventional radiology to achieve unparalleled precision in image-guided diagnosis and treatment while simultaneously reducing periprocedural morbidity. Molecular imaging, which provides valuable physiological and metabolic information alongside anatomical localization, can expand the capabilities of image-guided interventions. Among various molecular imaging techniques, positron emission tomography (PET) stands out for its superior spatial resolution and ability to acquire quantitative data. PET has emerged as a crucial tool for oncologic imaging and plays a pivotal role in both staging and the assessment of treatment responses. Typically used in combination with computed tomography (CT) (PET/CT) and occasionally with magnetic resonance imaging MRI (PET/MRI), PET as a hybrid imaging approach offers enhanced insights into disease progression and response. In recent years, PET has also found its way into image-guided interventions, especially within the rapidly expanding field of interventional oncology. This review aims to explore the current and evolving role of metabolic imaging, specifically PET, in interventional oncology. By delving into the unique advantages and applications of PET in guiding oncological interventions and assessing response, we seek to highlight the increasing significance of this modality in the realm of interventional radiology.


On the use of learning automata in the control of broadcast networks: a methodology.
Due to its fixed assignment nature, the well-known time division multiple access (TDMA) protocol suffers from poor performance when the offered traffic is bursty. In this paper, an adaptive TDMA protocol, which is capable of operating efficiently under bursty traffic conditions, is introduced. According to the proposed protocol, the station which is granted permission to transmit at each time slot is selected by means of learning automata (LA). The choice probability of the selected station is updated by taking into account the network feedback information. The system which consists of the LA and the network is analyzed and it is proven that the choice probability of each station asymptotically tends to be proportional to the probability that this station is not idle. Although there is no centralized control of the stations and the traffic characteristics are unknown and time-variable, each station tends to take a fraction of the bandwidth proportional to its needs. Furthermore, extensive simulation results are presented, which indicate that the proposed protocol achieves a significantly higher performance than other well-known TDMA protocols when operating under bursty traffic conditions.


A study of partial denture designs produced by an alumni group of dentists in health service practice.
Seventy-three dental surgeons working in general dental practice, all members of an alumni group, were given identical casts and produced designs for a mandibular partial denture. The designs were subsequently analysed and the dentists' skills in communicating their design intentions to technicians were also assessed. In this instance a preference for simple straightforward designs was demonstrated with a tendency to favour stereotype responses to detailed design challenges, which were not necessarily apposite. More recent graduates produced designs which were more likely to be understood by the technician.


Lung Cancer Screening in Brazil Comparing the 2013 and 2021 USPSTF Guidelines.
It is estimated that, from 2023 to 2025, lung cancer (LC) will be the second most frequent cancer in Brazil, but the country does not have an LC screening (LCS) policy. To compare the number of individuals eligible for screening, 5-year preventable LC deaths, and years of life gained (YLG) if LC death is averted by LCS, considering 3 eligibility strategies by sociodemographic characteristics. This comparative effectiveness research study assessed 3 LCS criteria by applying a modified version of the LC-Death Risk Assessment Tool (LCDRAT) and the LC-Risk Assessment Tool (LCRAT). Data are from the 2019 Brazilian National Household Survey. Participants included ever-smokers aged 50 to 80 years. Data analysis was performed from February to May 2023. Exposures included ever-smokers aged 50 to 80 years, US Preventive Services Task Force (USPSTF) 2013 guidelines (ever-smokers aged 55 to 80 years with ≥30 pack-years and <15 years since cessation), and USPSTF 2021 guidelines (ever-smokers aged 50 to 80 years with 20 pack-years and <15 years since cessation). The primary outcomes were the numbers of individuals eligible for LCS, the 5-year preventable deaths attributable to LC, and the number of YLGs if death due to LC was averted by LCS. In Brazil, the eligible population for LCS was 27 280 920 ever-smokers aged 50 to 80 years (13 387 552 female [49.1%]; 13 249 531 [48.6%] aged 50-60 years; 394 994 Asian or Indigenous [1.4%]; 3 111 676 Black [11.4%]; 10 942 640 Pardo [40.1%]; 12 830 904 White [47.0%]; 12 428 536 [45.6%] with an incomplete middle school education; and 12 860 132 [47.1%] living in the Southeast region); 5 144 322 individuals met the USPSTF 2013 criteria for LCS (2 090 636 female [40.6%]; 2 290 219 [44.5%] aged 61-70 years; 66 430 Asian or Indigenous [1.3%]; 491 527 Black [9.6%]; 2 073 836 Pardo [40.3%]; 2 512 529 [48.8%] White; 2 436 221 [47.4%] with an incomplete middle school education; and 2 577 300 [50.1%] living in the Southeast region), and 8 380 279 individuals met the USPSTF 2021 LCS criteria (3 507 760 female [41.9%]; 4 352 740 [51.9%] aged 50-60 years; 119 925 Asian or Indigenous [1.4%]; 839 171 Black [10.0%]; 3 330 497 Pardo [39.7%]; 4 090 687 [48.8%] White; 4 022 784 [48.0%] with an incomplete middle school education; and 4 162 070 [49.7%] living in the Southeast region). The number needed to screen to prevent 1 death was 177 individuals according to the USPSTF 2013 criteria and 242 individuals according to the USPSTF 2021 criteria. The YLG was 23 for all ever-smokers, 19 for the USPSTF 2013 criteria, and 21 for the USPSTF 2021 criteria. Being Black, having less than a high school education, and living in the North and Northeast regions were associated with increased 5-year risk of LC death. In this comparative effectiveness study, USPSTF 2021 criteria were better than USPSTF 2013 in reducing disparities in LC death rates. Nonetheless, the risk of LC death remained unequal, and these results underscore the importance of identifying an appropriate approach for high-risk populations for LCS, considering the local epidemiological context.


Rapid kinetic studies of SH oxidation-induced calcium release from sarcoplasmic reticulum vesicles.
We studied the kinetics of calcium release induced by SH oxidation in triads isolated from frog and rabbit skeletal muscle by measuring calcium fluxes by a fast filtration method. In both species SH oxidation induced release of 70-80% of the passively loaded calcium with a rate constant of 1 s-1. This rate constant is 3 times higher than the rate constant of calcium-induced calcium release and 15 times lower than the rate constant of ATP-induced release. Calcium release induced by SH oxidation exhibited the same calcium dependence of calcium-induced calcium release and was also inhibited by physiological [MG2+]. Neither SH oxidation-induced calcium release nor calcium-induced calcium release were regulated by luminal calcium. The redox state of thiol groups does not seem to control ATP-induced calcium release since the rate constant of calcium release after SH oxidation was not different from the rate constant measured in the presence of the reducing agent dithiothreitol. Our results do not support a role for SH oxidation, per se, as an essential step for the release of calcium from sarcoplasmic reticulum.


Progressive suppression of muscle glucose utilization during pregnancy.
Glucose utilization indices (GUIs) were measured in heart and a range of skeletal muscles in conscious, unrestrained, virgin or pregnant rats in the absorptive and post-absorptive phases. A clear effect of pregnancy to diminish muscle GUIs was identified, the magnitude of which was greatest in late gestation in the absorptive phase. Differences in the time courses and magnitudes of the response to pregnancy were observed between individual muscles. The effects of pregnancy are discussed in relation to an increased availability of lipid fuels and to decreased insulin and glucose concentrations.


Ultrasound-guided L5/S1 intradiscal needle placement using biplanar approach with the patient in the lateral decubitus position: A report of three cases.
The use of ultrasound (US)-guided intradiscal injection has been described in the literature with the patient lying in the prone position; however, many patients are unable to lie in the prone position. Therefore, we describe an innovative technique of US-guided platelet-rich plasma (PRP) administration in the lumbar intervertebral disc (IVD) of 3 patients with chronic lower back pain who failed to improve with conservative management. For all the 3 patients, magnetic resonance imaging showed annular tears of the L5/S1 IVD with broad-based central posterior protrusions. PRP injection was performed with the patients in the lateral decubitus position or modified recovery position. With the transducer initially placed in the short axis to the lumbar spine, the needle was inserted in-plane to the IVD, with the needle trajectory clearly visualized. Once the needle entered the annulus fibrosus, placement of the needle was confirmed by turning the transducer along the long axis of the spine to validate the location of the needle tip inside the IVD. Discus stimulation was performed with contrast administered to elicit each patient's usual pain, and spread of the contrast was confirmed under fluoroscopy. Upon confirmation of the intradiscal location, 3 ml of PRP was administered. This report described a novel technique demonstrating that US-guided lumbar intradiscal needle placement for PRP administration in patients lying in the lateral decubitus position is feasible.


Decreased baseline beta-lactamase production and inducibility associated with increased piperacillin susceptibility of Pseudomonas cepacia isolated from children with cystic fibrosis.
The incidence of pulmonary infections in children with cystic fibrosis caused by Pseudomonas cepacia, an organism which may possess an inducible beta-lactamase, has increased since 1978. Seven of 13 sputum isolates of P. cepacia from children with cystic fibrosis were classified as inducible by quantitative enzyme production following preincubation with 100, 200, or 400 micrograms/ml of cefoxitin. The recovery of inducible strains tended to be associated with recent ceftazidime therapy. Susceptibility to aztreonam, ceftazidime, and piperacillin alone or combined with the beta-lactamase inhibitors. YTR 830 or sulbactam, and isoelectric focusing for beta-lactamase were performed. Inducible isolates produced significantly more beta-lactamase than noninducible strains with or without the addition of cefoxitin. Noninducible isolates were more susceptible than inducible isolates to 8 micrograms/ml of piperacillin, a difference that was eliminated with the addition of either beta-lactamase inhibitor. Twelve of 13 strains produced a beta-lactamase band in the pH range of 7.9-8.1; no differences in satellite patterns were noted between the two groups of organisms. Increased production of beta-lactamase in the absence of an inducer may account for piperacillin resistance in P. cepacia in children with cystic fibrosis.


[Characteristics of duodenoplasty in duodenal ulcers of various localization].
Experience and methods of duodenoplasty in duodenal ulcers and pyloric stenosis are presented. Pylorus-saving duodenoplasty in combination with selective proximal vagotomy (SPV) can be performed in the majority of patients with duodenal ulcers. Pyloric sphincter is destroyed by ulcer rarely (7.2%). Removal of ulcerous substrate reduces significantly per cent of postoperative complications, including recurrence of ulcer. Long-term results (from 1 to 20 years) of pylorus-saving duodenoplasty with SPV in 259 patients with duodenal ulcer were analyzed. Low per cent of complications and lethal outcomes have been demonstrated.


[Clinical-epidemiological aspects of pityriasis versicolor (PV) in a fishing community of the semiarid region in Falcon State, Venezuela].
Between August 2001 and May 2002, the prevalence and several epidemiological and clinical characteristics of pityriasis versicolor (PV) were studied in 902 individuals aged two months- 60 years, 426 females and 476 males, from a fishery community of Río Seco, a semiarid region in the state of Falcon, north-western Venezuela. The overall prevalence of the disease was 15.52% (140/902). The frequency of infection was higher in females (65.7% vs. 34.3%), children under one year of age and adolescents (27.9% y 32.1%, respectively), and dark skin (67.9%). The most commonly affected anatomical areas were the face (57.9%) and thorax (27.1%). The most important clinical features of the disease were: hypochromic (91.4%), multicentric (73.6%), pruritic (92.9%), fine scaled (80.7%) and irregularly shaped borders (91.4%). On the basis of these results, the possible risk factors on transmission dynamic and maintenance of the disease endemically is discussed.


The inheritance of gossypol level in Gossypium. II. Inheritance of seed gosypol in two trains of cultivated Gossypoium barbadense L.
Two strains of cultivated Gossypium barbadense L., Sea Island AS-2 and Pima S-4, were used to study the effects of alleles at two loci on the production and/or storage of gossypol in mature embryos. The normal alleles, Gl(2) and Gl(3), are "native" to G. barbadense, whereas the mutant alleles, gl(2) and gl(3), were introduced from Gossypium hirsutum L. through backcrossing. Each strain was grown in three replications per trial, and one, Sea Island AS-2, was grown in three environments. Each experiment consisted of all possible crosses, including reciprocals, of the four true-breeding genotypes, plus parents. Additive effects accounted for more than 90% of the total genetic variance for seed gossypol level in all trials. Epistatic effects, though small, were frequently significant. In G. barbadense Gl(2) and Gl(3) were associated with the production of similar amounts of gossypol, whereas previous trials with cultivated varieties of G. hirsutum showed that Gl(2) was more than twice as expressive as Gl(3). The greater average productivity of seed gossypol in cultivated G. barbadense, as compared with G. hirsutum, was attributed to greater activity at the Gl(3) locus in the former species.


Multiple squamous cell carcinomas of the skin after therapy with sorafenib combined with tipifarnib.
Keratoacanthomas, as well as an actinic keratosis progressing to squamous cell cancer, have been reported in patients who were treated with sorafenib, a multikinase inhibitor known to suppress the actions of Raf kinase and vascular endothelial growth factor receptor. We describe a 70-year-old white woman with metastatic renal cell carcinoma who was treated with a combination of sorafenib and tipifarnib (a farnesyltransferase inhibitor). She had no history of skin cancer. However, within 3 months after starting this therapy, she developed 3 erythematous nodules on her legs. Pathologic examination showed deeply invasive, well-differentiated squamous cell carcinomas. The tumors were excised, and sorafenib-tipifarnib treatment was discontinued. No new lesions have developed to date. Targeted agents, such as sorafenib and tipifarnib, are increasingly being used in the management of visceral malignant neoplasms. A temporal relationship was observed between the initiation of the targeted treatments and the emergence of these cutaneous cancers. Further study of the mechanisms responsible for the rapid appearance of squamous cell cancers in this setting may provide insights into the pathogenesis of skin tumors.


Induction of the nodA promoter of Rhizobium leguminosarum Sym plasmid pRL1JI by plant flavanones and flavones.
An expression vector containing the Rhizobium leguminosarum nodA promoter cloned in front of the Escherichia coli lacZ gene was used to characterize the properties of the R. leguminosarum nodA gene-inducing compound(s) present in sterile root exudate of the host plant Vicia sativa L. subsp. nigra (L.). The major inducing compound was flavonoid in nature, most likely a flavanone. The commercially available flavonoids naringenin (5,7,4'-trihydroxyflavanone), eriodictyol (5,7,3'4'-tetrahydroxyflavanone), apigenin (5,7,4'-trihydroxyflavone), and luteolin (5,7,3',4'-tetrahydroxyflavone) induced the nodA promoter to the same level as the root exudate. On the basis of chromatographic properties, it was concluded that none of these compounds is identical to the inducer that is present in root exudate. The induction of the nodA promoter by root exudate and by the most effective inducer naringenin was very similar, as judged from the genetic requirements and the kinetics of induction.


Predictive value of margins in diagnostic biopsies of nonmelanoma skin cancers.
With geographic regional variation, nonmelanoma skin cancer biopsy reports include assessment of margins. When margins are reported as negative, clinical dilemmas may emerge concerning the necessity of additional treatment. To evaluate the predictive value of biopsy margins with regard to residual tumor present in subsequent excisions of nonmelanoma skin cancers. This is a retrospective review of 235 diagnostic nonmelanoma skin cancer biopsies and their corresponding excisions for margin status at biopsy, and the presence of residual tumor in subsequent excisions. Twelve of 148 squamous cell carcinomas (8.1%) had negative biopsy margins and all of the subsequent excisions were free of residual tumor. The squamous cell carcinomas with negative biopsy margins consisted predominantly of nonfacial, superficial tumors of the well-differentiated and keratoacanthoma subtype. Nine of 87 basal cell carcinomas (10.3%) had negative biopsy margins. Seven of those 9 (77.8%) had residual tumor present in subsequent excisions. Statistical analysis performed reached significance, but with small sample size as only 21 of the biopsy specimens had negative margins. Also, residual tumor was determined via standard bread-loafing technique on excisions, which is known to examine only a proportion of the tissue and can lead to false-negative results. The results of this small pilot study suggest that negative-margin diagnostic biopsies may be therapeutic for well-differentiated or keratoacanthoma subtypes of squamous cell carcinoma because all subsequent excisions were devoid of tumor. Negative biopsy margins from basal cell carcinomas were not predictive of tumor removal.


Neural disturbances in chickens caused by dietary T-2 toxin.
Graded concentrations of dietary T-2 toxin (0, 1, 2, 4, 8, and 16 mug/g) were fed to groups of 40 chickens. T-2 toxin was found to cause an abnormal positioning of the wings, hysteroid seizures, and impaired righting reflex in young chickens. The abnormal wing positioning occurred spontaneously or as the result of dropping from a height of 1 meter. The seizures could be elicited by rough handling or loud noises. The seizures and the abnormal wing posture would not occur again when the stimulus was repeated unless a rest period of 3 to 6 h was allowed. The loss of righting reflex could be demonstrated at any time. The total incidence of neural symptoms was dependent on the length of exposure to T-2 toxin and to its concentration. Neural toxicity occurred at dosages of 4, 8, and 16 mug per g of diet, which are the same doses that retard growth. This neural toxicity of T-2 toxin in chickens is similar to the neural disturbances associated with alimentary toxic aleukia, a nutritional toxicosis of humans produced by eating moldy grain. T-2 toxin has been implicated also in moldy corn toxicosis which has neural manifestations in horses and swine.


Regulation of differentiation in normal and transformed erythroid cells.
Studies are described employing two erythropoietic systems to elucidate regulatory mechanisms that control both normal erythropoiesis and erythroid differentiation of transformed hemopoietic precursors. Evidence is provided suggesting that normal erythroid cell precursors require erythropoietin as a growth factor that regulates the number of precursors capable of differentiating. Murine erythroleukemia cells proliferate without need of erythropoietin; they show a variable, generally low, rate of spontaneous differentiation and a brisk rate of erythropoiesis in response to a variety of chemical agents. Present studies suggest that these chemical inducers initiate a series of events including cell surface related changes, alterations in cell cycle kinetics, and modifications of chromatin and DNA structure which result in the irreversible commitment of these leukemia cells to erythroid differentiation and the synthesis of red-cell-specific products.


Endometrial carcinoma in women 40 years of age or younger.
Adenocarcinoma of the endometrium in patients 40 years of age or younger is rare and accounts for 2.9% of all endometrial cancers diagnosed in the study community. However, the diagnosis of malignancy was confirmed in only 32 of 54 patients (59.2%) with pathologic material available for review. None of the 32 patients had Stein-Leventhal syndrome or was receiving sequential oral contraceptives. Obesity was found in only 37.5%, nulligravidity in 37.5%, and hypertension in 25%. In 81%, the presenting symptom was abnormal vaginal bleeding, and 6 patients (19%) had coexisting ovarian neoplasms (4 endometrioid carcinomas, 1 mucinous cystadenocarcinoma, and 1 adenocarcinoma arising in a cystic teratoma). Atypical endometrial hyperplasia, previously interpreted as well-differentiated adenocarcinoma, was diagnosed in 11 of 22 patients. The pathologic criteria for establishing a diagnosis of atypical endometrial hyperplasia and distinguishing it from well differentiated adenocarcinoma of the endometrium are emphasized. Thirteen of 32 patients received no radiation therapy and none developed pelvic recurrence or metastatic tumor. The 2 deaths from tumor were in patients with stage 3 ovarian cancer, and no patients died of endometrial carcinoma. The current policy is to treat patients with atypical endometrial hyperplasia and well-differentiated adenocarcinoma (clinical stage I, pathology confirmed) by hysterectomy without irradiation treatment. Because of 6 of the 32 patients (19%) had coexisting ovarian neoplasms, careful examination of the adnexa at the time of clinical staging is emphasized.


Pancreatic Cystic Lesions: New Endoscopic Trends in Diagnosis.
The diagnosis of incidental pancreatic cystic lesions is increasing in the general population because of the routine use of cross-sectional imaging modalities. Not all cysts are neoplastic, and the majority of cystic neoplasms have a low overall likelihood of progression to malignancy. Current management is based on imaging and cyst fluid analysis, but we are not able to diagnose the specific type of cyst and its malignant potential in a significant number of patients. Better diagnostic tools are required to avoid unnecessary surgical resections that carry an important risk of morbidity and mortality. Herein we review current evidence concerning the use of new endoscopic modalities for the evaluation of pancreatic cystic lesions. We focus our discussion on the new cyst fluid markers, and the advancements on modalities such as confocal endomicroscopy, contrast-enhanced endoscopic ultrasound, and the use of Spyglass. We also discuss the use of new devices to improve the cellular yield from cyst fluid and to obtain cyst-wall tissue, namely the cytology brush, the fine needle biopsy, and forceps for cyst-wall biopsy.


Obstructive Sleep Apnea in Developmental Age: 22-Item Pediatric Sleep Questionnaire for an Observational Descriptive Investigation.
The aim of this paper is to perform an observational descriptive study of the Obstructive Sleep Apnea Syndrome (OSAS) in a population of children by evaluating the prevalence and role of sex and age variables. The 22-item Pediatric Sleep Questionnaire (PSQ) was administered to parents of children aged 3 to 12 years. The questionnaire is a very simple tool since it allows for the indication of patients with possible OSAS diagnosis through a cut-off of 0.33. The anonymous diagnostic questionnaire, available in digital format, was administered to the population under study by a link or QR code. Only the questionnaires completed in all their parts were recorded and analyzed. Eight hundred and thirty-two questionnaires were collected. One hundred and fifty-four subjects obtained a PSQ score > 0.33 and the prevalence of OSAS was 18.51%. The Chi-square test showed a statistically significant association between the PSQ score > 0.33 and male sex. The higher prevalence of subjects with a value of PSQ > 0.33 (n = 277) are aged 3-4-5 years, followed by the 6-7-8 range in the group with PSQ score > 0.33, p < 0.05. The prevalence of OSAS was 18.51% in children aged 3 to 12 years. The variables male biological sex and the age group 3-8 year were statistically significant for subjects with OSAS diagnosis. This study underlines the use of the 22-item Pediatric Sleep Questionnaire as a first screening tool to identify children at risk of OSAS.


Engaging One Health for Non-Communicable Diseases in Africa: Perspective for Mycotoxins.
The role of mycotoxins-e.g., aflatoxins, ochratoxins, trichothecenes, zearalenone, fumonisins, tremorgenic toxins, and ergot alkaloids-has been recognized in the etiology of a number of diseases. In many African countries, the public health impact of chronic (indoor) and/or repeated (dietary) mycotoxin exposure is largely ignored hitherto, with impact on human health, food security, and export of African agricultural food products. Notwithstanding, African scientific research reached milestones that, when linked to findings gained by the international scientific community, make the design and implementation of science-driven governance schemes feasible. Starting from Nigeria as leading African Country, this article (i) overviews available data on mycotoxins exposure in Africa; (ii) discusses new food safety issues, such as the environment-feed-food chain and toxic exposures of food producing animals in risk assessment and management; (iii) identifies milestones for mycotoxins risk management already reached in West Africa; and (iv) points out preliminary operationalization aspects for shielding communities from direct (on health) and indirect (on trade, economies, and livelihoods) effects of mycotoxins. An African science-driven engaging of scientific knowledge by development actors is expected therefore. In particular, One health/One prevention is suggested, as it proved to be a strategic and sustainable development framework.


Hidden diversity in sardines: genetic and morphological evidence for cryptic species in the goldstripe sardinella, Sardinella gibbosa (Bleeker, 1849).
Cryptic species continue to be uncovered in many fish taxa, posing challenges for fisheries conservation and management. In Sardinella gibbosa, previous investigations revealed subtle intra-species variations, resulting in numerous synonyms and a controversial taxonomy for this sardine. Here, we tested for cryptic diversity within S. gibbosa using genetic data from two mitochondrial and one nuclear gene regions of 248 individuals of S. gibbosa, collected from eight locations across the Philippine archipelago. Deep genetic divergence and subsequent clustering was consistent across both mitochondrial and nuclear markers. Clade distribution is geographically limited: Clade 1 is widely distributed in the central Philippines, while Clade 2 is limited to the northernmost sampling site. In addition, morphometric analyses revealed a unique head shape that characterized each genetic clade. Hence, both genetic and morphological evidence strongly suggests a hidden diversity within this common and commercially-important sardine.


Plant functional types do not predict biomass responses to removal and fertilization in Alaskan tussock tundra.
Plant communities in natural ecosystems are changing and species are being lost due to anthropogenic impacts including global warming and increasing nitrogen (N) deposition. We removed dominant species, combinations of species and entire functional types from Alaskan tussock tundra, in the presence and absence of fertilization, to examine the effects of non-random species loss on plant interactions and ecosystem functioning.After 6 years, growth of remaining species had compensated for biomass loss due to removal in all treatments except the combined removal of moss, Betula nana and Ledum palustre (MBL), which removed the most biomass. Total vascular plant production returned to control levels in all removal treatments, including MBL. Inorganic soil nutrient availability, as indexed by resins, returned to control levels in all unfertilized removal treatments, except MBL.Although biomass compensation occurred, the species that provided most of the compensating biomass in any given treatment were not from the same functional type (growth form) as the removed species. This provides empirical evidence that functional types based on effect traits are not the same as functional types based on response to perturbation. Calculations based on redistributing N from the removed species to the remaining species suggested that dominant species from other functional types contributed most of the compensatory biomass.Fertilization did not increase total plant community biomass, because increases in graminoid and deciduous shrub biomass were offset by decreases in evergreen shrub, moss and lichen biomass. Fertilization greatly increased inorganic soil nutrient availability.In fertilized removal treatments, deciduous shrubs and graminoids grew more than expected based on their performance in the fertilized intact community, while evergreen shrubs, mosses and lichens all grew less than expected. Deciduous shrubs performed better than graminoids when B. nana was present, but not when it had been removed.Synthesis. Terrestrial ecosystem response to warmer temperatures and greater nutrient availability in the Arctic may result in vegetative stable-states dominated by either deciduous shrubs or graminoids. The current relative abundance of these dominant growth forms may serve as a predictor for future vegetation composition.


Value of sports pre-participation examination in health care for adolescents.
Though adolescence is typically perceived as a time of good health in many places in the world,the reality is that adolescents have many health problems, including medical and behavioral disorders. The ideal location for health maintenance visits is the office of a clinician who has an established relationship with the adolescent patient. The clinician can use the interest of youth for sports to improve the health care of these youth in various ways, as reviewed in this article. A sports pre-participation examination (PPE) is recommended before the adolescent engages in organized sports. During this evaluation, various issues can be covered, including anticipatory guidance for sports participation, stress involved with organized sports, drug or supplement abuse in sports, eating disorders, and weight control practices, in-jury prevention, principles of sports participation, the importance of regular physical activity and normal growth and development. The pre-participation examination is reviewed in this article, including taking a proper history, performing the physical examination, and ordering appropriate laboratory tests. Youth with medical illnesses can be clinician-directed to the sports activities that are best and safest for them. Keeping youth active in some type of physical activity is important and thus, the examination can be used to allow full or partial participation in all or only some sports. This paper summarizes the clinician's approach to using sports activities as a way of improving the health of youth.


[Self-perceived work disability in a school of children with special needs].
Increased psychosocial and physical demands of the Special Education Centers (SEC) workers can also lead to intense involvement, triggering stressful and to trigger stress situations and potentially work disability. The objective of this study was to assess the self-perceived occupational disability and its relation with socio-demographic, occupational and health variables with in a sample of this these workers. Cross-sectional study with of 40 SEC workers of in Murcia (Spain) (n = 40). The Spanish WRFQ version was used to measure self-perceived work ability. A structured self-administered questionnaire was used for to collect sociodemographic, occupational, and health variables. A descriptive analysis of the studied variables was performed. Differences between groups were studied using the Mann-Whitney U test, Student's T test and Kruskal-Wallis test. The mean age of the sample was 40.15 ± 10.53 years; 82.5% were women, 60% were computer users and 92.50% were directly attending children. The subscales of production requirements and physical demands had the worst results. Workers <40 years presented lower scores in for the time management subscales (p = 0.002) and production requirements (p = 0.01); computer users in time management (p <0.001), production requirements (p <0.001) and psychological requirements (p = 0.005); as well as among those working as managers and healthcare employeesthe employment status of executive and sanitary. The level of self-perceived occupational disability is was low in this collective, with the subscales of production requirements and physical requirements being the worst evaluated. The working conditions related to a higher degree of self-perceived occupational disability are were the use of of a computer, the employment status and the manual materials handling.


[Change in energy metabolism of ascites cancer cells with a decrease in pH].
In Hank's balanced salt solution EL-4 ascites thymoma cells possessed endogenous respiration which was sufficient for the maintenance of their ATP level: pH decrease down to 6.0 had no effect either on endogenous respiration or the ATP level. Glucose had no influence on the respiration of EL-4 cells but inhibited that of Ehrlich ascites carcinoma (EAC) cells by 40% (Crabtree effect); respiration of the both cell lines was strongly (4-fold) inhibited after simultaneous addition of glucose, lactate and pH decrease. EL-4 cells had no endogenous glycolysis; EAC cells showed a low level of glycolysis only after pH decrease. Glucose addition led to activation of glycolysis (both inhibited 2-fold after a decrease of pH down to 6.0. The respiration inhibition at pH 7.3 and 6.0 caused no decrease of ATP depletion when glucose was present in the medium; this result may be due to suppression of ATP consumption. Incubation of EL-4 cells under respiration and glycolysis deficiency conditions resulted in a sharp ATP depletion; pH decrease delayed this depletion.


[Thalassotherapy: long-term developments].
The currently available medical technologies for the rehabilitative and balneological treatment of osteoarthrosis enable specialists to significantly suppress the activity of inflammatory and destructive process, reduce severity of pain syndrome, improve functional abilities of the patients, prevent the further development of the disease, and increase the overall efficiency of health resort-based therapy by 18-20%.


Assessment of the Efficiency of Chemical and Thermochemical Depolymerization Methods for Lignin Valorization: Principal Component Analysis (PCA) Approach.
Energy demand and the use of commodity consumer products, such as chemicals, plastics, and transportation fuels, are growing nowadays. These products, which are mainly derived from fossil resources and contribute to environmental pollution and CO2 emissions, will be used up eventually. Therefore, a renewable inexhaustible energy source is required. Plant biomass resources can be used as a suitable alternative source due to their green, clean attributes and low carbon emissions. Lignin is a class of complex aromatic polymers. It is highly abundant and a major constituent in the structural cell walls of all higher vascular land plants. Lignin can be used as an alternative source for fine chemicals and raw material for biofuel production. There are many chemical processes that can be potentially utilized to increase the degradation rate of lignin into biofuels or value-added chemicals. In this study, two lignin degradation methods, CuO-NaOH oxidation and tetramethyl ammonium hydroxide (TMAH) thermochemolysis, will be addressed. Both methods showed a high capacity to produce a large molecular dataset, resulting in tedious and time-consuming data analysis. To overcome this issue, an unsupervised machine learning technique called principal component analysis (PCA) is implemented.


Carrier-envelope phase stable few-cycle pulses at 400 kHz for electron-ion coincidence experiments.
Coincident electron-ion detection after photoionization in a "reaction microscope" is a very powerful tool to study atomic and molecular dynamics. However, the implementation of this tool in the field of attosecond science has so far been rather limited, due to the lack of high repetition rate laser sources capable of delivering few-cycle pulses with sufficient energy per pulse. In this article, the development of a Non-collinear Optical Parametric Amplifier (NOPA) capable of delivering Carrier-Envelope Phase (CEP) stable pulses with sub-6 fs duration and pulse energies in the few-µJ range is presented. The potential of combining the high repetition rate source and a reaction microscope operating at this high frequency is demonstrated in a proof-of-principle experiment on strong field ionization of Ar atoms.


Dissecting structural and nucleotide genome-wide variation in inbred Iberian pigs.
In contrast to international pig breeds, the Iberian breed has not been admixed with Asian germplasm. This makes it an important model to study both domestication and relevance of Asian genes in the pig. Besides, Iberian pigs exhibit high meat quality as well as appetite and propensity to obesity. Here we provide a genome wide analysis of nucleotide and structural diversity in a reduced representation library from a pool (n=9 sows) and shotgun genomic sequence from a single sow of the highly inbred Guadyerbas strain. In the pool, we applied newly developed tools to account for the peculiarities of these data. A total of 254,106 SNPs in the pool (79.6 Mb covered) and 643,783 in the Guadyerbas sow (1.47 Gb covered) were called. The nucleotide diversity (1.31x10-3 per bp in autosomes) is very similar to that reported in wild boar. A much lower than expected diversity in the X chromosome was confirmed (1.79x10-4 per bp in the individual and 5.83x10-4 per bp in the pool). A strong (0.70) correlation between recombination and variability was observed, but not with gene density or GC content. Multicopy regions affected about 4% of annotated pig genes in their entirety, and 2% of the genes partially. Genes within the lowest variability windows comprised interferon genes and, in chromosome X, genes involved in behavior like HTR2C or MCEP2. A modified Hudson-Kreitman-Aguadé test for pools also indicated an accelerated evolution in genes involved in behavior, as well as in spermatogenesis and in lipid metabolism. This work illustrates the strength of current sequencing technologies to picture a comprehensive landscape of variability in livestock species, and to pinpoint regions containing genes potentially under selection. Among those genes, we report genes involved in behavior, including feeding behavior, and lipid metabolism. The pig X chromosome is an outlier in terms of nucleotide diversity, which suggests selective constraints. Our data further confirm the importance of structural variation in the species, including Iberian pigs, and allowed us to identify new paralogs for known gene families.


Analysis of liver transplantation.
Liver transplantation has been developed to the point of a service operation, the exploitation of which depends upon the establishment of multiple regional centers. The increased use of this procedure will permit the delivery of optimum health care to victims of endstage liver disease.


Influence of lifestyle, coping, and job stress on blood pressure in men and women.
We designed this study to clarify the role of work stress on long-term blood pressure control and in particular to investigate whether perceived work stress directly affected resting blood pressure levels or whether there were indirect effects mediated by coping mechanisms and lifestyle. Men (n = 337) and women (n = 317) working in a government tax office completed questionnaires for assessment of work-related stress, coping strategies, and lifestyle. Seven resting blood pressure measurements were recorded serially on each of two occasions a week apart. Men had higher blood pressures (119.6/68.6 versus 110.9/65.6 mm Hg) than women; they used more "maladaptive" coping strategies, drank more alcohol, and ate less healthily but exercised more than women. There were no direct associations between measures of work stress and blood pressure. In univariate and regression analyses, both body mass index and lifestyle factors in the form of alcohol consumption, exercise, and diet were related to blood pressure in men and women. Various "adaptive" or "maladaptive" coping mechanisms were identified and independently related to both job stress and blood pressure levels. Women were more likely to use "healthier" or adaptive coping mechanisms than men. Thus, work stress per se had no direct effect on blood pressure, but the ways that individuals reported coping with stress were significantly related to blood pressure, with blood pressure elevation effects appearing to be mediated largely by dietary and drinking habits and physical inactivity. The results point to the need to target individual coping strategies and lifestyle as much as the working environment in workplace cardiovascular health promotion programs.


Poor outcome of very low birthweight babies with serious congenital heart disease.
To evaluate incidence and mortality of congenital heart disease in very low birthweight babies. Retrospective analysis of a 12 year period. Forty seven babies were diagnosed with severe congenital heart disease. The most common lesions were ventricular septal defect and coarctation of the aorta. Mortality attributed to congenital heart disease was 32%. Coarctation of the aorta, the second most common lesion, was fatal in 62% of cases. Closure of a patent ductus arteriosus with indomethacin proved to be detrimental in babies with undiagnosed coarctation, causing rapid deterioration in some. Very low birthweight neonates with severe congenital heart disease have a higher mortality than babies with higher birth weight. A contributing factor is closure of a patent ductus arteriosus if an underlying lesion has not been recognised. This could be of significance if the use of prophylactic treatment with indomethacin becomes more common.


Effects of puerarin on lipopolysaccharide-induced myocardial dysfunction in isolated rat hearts.
Myocardial dysfunction is a serious complication induced by sepsis. Puerarin is an oriental medicine that possesses therapeutic benefits for cardiovascular diseases. The aim of this study was to evaluate the anti-myocardial dysfunction effects of puerarin in isolated rat hearts induced by lipopolysaccharide- and compare the myocardial protective effects between the different concentrations of puerarin. Isolated hearts were attached to a Langendorff apparatus and perfused with lipopolysaccharide (LPS) and different concentrations of puerarin. The hemodynamic parameters of heart rate (HR), left ventricular end systolic pressure [LVESP], +dp/dtmax, and -dp/dtmax were recorded. The biochemical indexes of lactic dehydrogenase (LDH), tumor necrosis factor alpha (TNF-α), and creatine kinase (CK) in the coronary effluent were measured at 40, 90, and 120 min of perfusion. TNF-α in myocardial tissues was measured after perfusion was completed. As a result, puerarin (0.24 μmmol/L-0.48 μmmol/L) significantly increased LVESP, +dp/dtmax, -dp/dtmax, and HR in isolated rat hearts that were declined by LPS during perfusion periods. Puerarin could protect against increased LDH, CK, and TNF-α in coronary effluent of isolated rat hearts by LPS during perfusion periods. Treatment of 0.48 μmmol/L puerarin significantly decreased the TNF-α in coronary effluent of isolated rat hearts compared with the treatment of 0.12 and 0.24 μmmol/L puerarin, but the TNF-α values were not reverted to baseline levels. However, the difference of TNF-α in myocardial tissue in the three puerarin-combined groups was statistically significant. This study confirms that puerarin can improve LPS-induced contractile dysfunction in isolated heart and inhibit LPS-stimulated myocardial TNF-α production.


Serology of oral Actinobacillus actinomycetemcomitans and serotype distribution in human periodontal disease.
Actinobacillus actinomycetemcomitans from the human oral cavity was serologically characterized with rabbit antisera to the type strain NCTC 9710; a number of reference strains, including Y4, ATCC 29522, ATCC 29523, ATCC 29524, NCTC 9709; and our own isolates representative of each of 10 biotypes. Using immunoabsorbed antisera, we identified three distinct serotypes by immunodiffusion and indirect immunofluorescence. Serotype a was represented by ATCC 29523 and SUNYaB 75; serotype b was represented by ATCC 29522 and Y4; and serotype c was represented by NCTC 9710 and SUNYaB 67. Indirect immunofluorescence revealed no reaction between the three A. actinomycetemcomitans serotype-specific antisera and 62 strains representing 23 major oral bacterial species. Distinct from the serotype antigens were at least one A. actinomycetemcomitans species common antigen and an antigen shared with other Actinobacillus species, Haemophilus aphrophilus, and Haemophilus paraphrophilus. All serotype a A. actinomycetemcomitans strains failed to ferment xylose, whereas all serotype b organisms fermented xylose. Serotype c included xylose-positive as well as xylose-negative strains. A total of 301 isolates of A. actinomycetemcomitans from the oral cavity of 74 subjects were serologically categorized by indirect immunofluorescence with serotype-specific rabbit antisera. Each patient harbored only one serotype of A. actinomycetemcomitans. Fourteen healthy subjects, five diabetics, and seventeen adult periodontitis patients exhibited serotypes a and b in approximately equal frequency, whereas serotype c was found less frequently. In contrast, in 29 localized juvenile periodontitis patients, the incidence of serotype b was approximately two times higher than that of serotypes a or c, suggesting a particularly high periodontopathic potential of A. actinomycetemcomitans serotype b strains. In subjects infected with A. actinomycetemcomitans, serum antibodies were detected to the serotype antigens, indicating that these antigens may play a role in the pathogenesis of periodontal disease.


Impairment of hepatic insulin receptors during chronic ethanol administration.
Chronic alcoholism is frequently associated with impaired intermediary metabolism and insulin resistance. The cellular defects leading to insulin resistance have not been clearly defined but could result from reduced insulin binding or abnormalities in any one of several postreceptor steps. The purpose of the present studies was to measure 125I-insulin binding and internalization kinetics and postreceptor response of the enzyme activity of tyrosine aminotransferase in isolated cultured rat hepatocytes. Four weeks of alcohol ingestion significantly reduced to 47% of control the 125I-insulin binding sites measured either as surface or total (after digitonin permeabilization). In contrast, 125I-epidermal growth factor binding was not significantly changed. Internalization of surface-bound 125I-insulin was decreased, but degradation was not increased, indicating that altered kinetics did not account for the change. Ethanol ingestion markedly reduced in liver cytosol some enzymes regulated by insulin and involved in glucose homeostasis. Basal activities of tyrosine aminotransferase and glucokinase were reduced 51% (P less than 0.01) and 32% (P less than 0.01), respectively. In contrast, phosphoenolpyruvate carboxykinase was unchanged. In short-term cultured hepatocytes from ethanol-fed rats, the maximum response of tyrosine amino-transferase to insulin was reduced 40% (P less than 0.01) without a change in the concentration causing 50% of the maximum response (EC50) compared with controls. In contrast, dexamethasone increased tyrosine aminotransferase to similar maximal levels and with similar EC50, indicating that ethanol did not alter the intracellular response. In conclusion, chronic ethanol ingestion caused significant time-dependent and selective changes in cell surface binding of insulin that was associated with subsequent postreceptor events.


The influence of surgery on the natural history of angiographically documented left ventricular aneurysm: the Coronary Artery Surgery Study.
Coronary artery bypass surgery with or without aneurysmectomy has been used to treat patients with angiographically defined left ventricular aneurysm. To evaluate whether surgery benefits such patients, we analyzed the data from 1131 patients who were enrolled in the registry of the Coronary Artery Surgery Study. Four hundred sixty-seven patients underwent bypass surgery, of which 238 also had left ventricular resection, and 30 had resection alone. The overall operative mortality was 7.9%; the operative mortality was 7% for bypass alone compared with 9% for bypass surgery plus left ventricular resection (NS). Long-term survival by life-table analysis was similar for both medically and surgically treated patients (69% vs 67%, respectively). Cox survival analysis identified congestive heart failure score, duration of chest pain, extent of coronary disease, left ventricular end-diastolic pressure, age, and surgical therapy as important predictors of outcome. Patient subsets that showed improved survival with surgical therapy after adjustment for inequities in baseline characteristics were patients with three-vessel disease and those patients in moderate- and high-risk subgroups. Surgical therapy significantly reduced symptoms of angina and use of cardiac medications but the incidence of recurrent infarction was similar for both therapies.


Post-transcriptional regulation of H-ferritin gene expression in human monocytic THP-1 cells by protein kinase C.
The mRNA coding for H-ferritin was highly induced in human monocytic THP-1 cells following treatment with phorbol 12-myristate 13-acetate (PMA). The induction was detected at 3 h, reached maximal levels at 12 h, and was sustained for up to 48 h subsequent to PMA exposure. PMA-induced up-regulation of H-ferritin gene expression was also observed in other leukaemic cell lines, HL60 and U937, but not in non-leukaemic cell types, including human fibroblasts, endothelial cells and smooth muscle cells. The effect of PMA could be completely blocked by the protein kinase C inhibitor, H-7. Furthermore, treatment of THP-1 cells with bacterial phospholipase C also produced a marked increase in expression of H-ferritin mRNA, suggesting the activation of protein kinase C was responsible for the accumulation of mRNA. Nuclear run-off experiments demonstrated that PMA did not increase the transcriptional rate of the H-ferritin gene. In contrast, the half-life of the H-ferritin mRNA measured in the presence of actinomycin D was greatly prolonged in PMA-treated cells. The induction of H-ferritin mRNA by PMA required no protein synthesis. Conversely, treatment of THP-J cells with protein synthesis inhibitor, cycloheximide, resulted in a 4-5-fold increase in H-ferritin mRNA. The increase in the stability of the H-ferritin mRNA was also observed in cells treated with cycloheximide. Taken together, these results suggest that the stability of H-ferritin mRNA in THP-1 is subjected to regulation via a protein kinase C-mediated phosphorylation on existing putative protein factor(s).


[Risk factors associated, diagnostic methods and treatment for endometriosis, used in clinical service endometriosis gynecology Hospital General de Mexico (2009-2011)].
Endometriosis no ectopic endometrial stroma and glands. Have different risk factors. Four theories explain it: the theory of coelomic metaplasia, embryonic cell debris, deployment and immunological. Clinical data are pain and infertility. For the American Fertility Society (AFS) is divided into minimal, mild, moderate and severe. Diagnostic studies are antigen Ca 125, Magnetic Resonance, and abdominal ultrasound. The ideal method is direct visualization with histological confirmation. The medical and surgical treatment. To determine the risk factors, diagnosis of Endometriosis and effectiveness of treatments used in clinical Endometriosis Gynecology Unit at the General Hospital of Mexico OD. A descriptive, longitudinal and retrospective duration of 2 years 6 months in 30 patients diagnosed with endometriosis in the clinical treatment of Endometriosis General Hospital of Mexico OD. The most affected age group was 21 to 25 years, the risk factors are Gesta 1, a resident of Mexico, Mullerian malformation. The symptom was dysmenorrhea. In 16 were diagnosed as a surgical finding and laparoscopically diagnosed. It is important to study the risk factors. The diagnosis is made using clinical data, quantification of CA125 antigen and imaging studies. Medical treatment is indicated both in the preoperative as well as postoperative surgical treatment and seeks to eradicate the lesions.


Genetic polymorphism in patients with early and late onset of ulcerative colitis.
The aim was to investigate SNPs of TLR-2,3,4, NOD2/CARD15, JAK-2, and IL-10 in patients with the early and late UC onset. Matherials and methods: 126 patients with UC were investigated. To assess the predisposition of the early and late UC onset the incidence of the following SNPs: Arg753Gln TLR2 gene, Phe412Leu TLR3 gene, Asp299Gly and Thr399Ile TLR4 gene, C-819T, G-1082A and C-592A gene IL-10, Val617Phe gene JAK2, Gly908Arg gene NOD2/CARD15 were analyzed. Results: 76 patients had early disease onset and 50 had a late one. SNPs of TLR3 were observed in 50.8% cases. TLR4 polymorphism was more common than TLR3, and was observed in 81 (64.3%) UC patients. Polymorphism of NOD2/CARD15 and IL-10 genes were revealed with almost the same frequency 49 (38.9%) and 50 (39.9%) patients, respectively. Conclusions: Polymorphisms of TLR-2,3 genes and TLR4 Asp299Gly, NOD2/CARD15 prevailed in patients with the late UC onset that allows to suppose that bacterial flora plays one of the key roles in modification of immune response and UC development. In patients with early UC onset polymorphisms of the JAK2 and IL-10 genes prevailed responsible for the cytokine cascade activation and cause the immune mechanism that might lead to a more aggressive course of the disease.


Creation of a potato mutant lacking the starch branching enzyme gene StSBE3 that was generated by genome editing using the CRISPR/dMac3-Cas9 system.
The potato tuber starch trait is changed depending on the composition of amylose and amylopectin. The amount of amylopectin is determined by the activity of the starch branching enzymes SBE1, SBE2, and SBE3 in potato. SBE3, a homolog of rice BEI, is a major gene that is abundant in tubers. In this study, we created mutants of the potato SBE3 gene using CRISPR/Cas9 attached to the translation enhancer dMac3. Potato has a tetraploid genome, and a four-allele mutant of the SBE3 gene is desired. Mutations in the SBE3 gene were found in 89 of 126 transformants of potato plants. Among these mutants, 10 lines contained four mutant SBE3 genes, indicating that 8% efficiency of target mutagenesis was achieved. These mutants grew normally, similar to the wild-type plant, and yielded sufficient amounts of tubers. The potato starch in these tubers was similar to that of the rice BEI mutant. Western blot analysis revealed the defective production of SBE3 in the mutant tubers, suggesting that these transformants were loss-of-function mutants of SBE3.


Secretome analysis of novel IgE-binding proteins from Penicillium citrinum.
The Penicillium genus of fungi is a frequently reported cause of allergic reactions. However, only a limited number of allergens have been reported. In Penicillium spp., many allergens show higher IgE-binding activity in culture filtrate extracts than in cellular extracts. In order to investigate the IgE-reactive profile of mold-sensitized patients, secreted IgE-reactive proteins from Penicillium citrinum were identified by 2-DE, serum immunoblotting, and nanoLC-MS/MS. Among the IgE-reactive spots, one known allergen, Pen c 13, and four novel allergens were identified. The cDNAs coding for Pen c 32 and Pen c 30 were cloned using designed primers based on nanoLC-MS/MS analysis. The amino acid sequences of Pen c 32 and Pen c 30 were, respectively, found to have extensive similarity with those of pectate lyases and catalases from various fungi. Native Pen c 30 was shown to have catalase activity and to bind to serum IgE from 48% of mold-allergic patients and induced immediate type skin reactions in a sensitized patient. Here, we present a proteome approach which resulted in the identification of four novel secreted allergens. These novel allergens might be useful in allergy diagnosis and in the treatment of mold-allergic disorders.


Exploring the role of COVID-19 pandemic-related changes in social interactions on preschoolers' emotion labeling.
During the COVID-19 pandemic people were increasingly obliged to wear facial masks and to reduce the number of people they met in person. In this study, we asked how these changes in social interactions are associated with young children's emotional development, specifically their emotion recognition via the labeling of emotions. Preschoolers labeled emotional facial expressions of adults (Adult Faces Task) and children (Child Faces Task) in fully visible faces. In addition, we assessed children's COVID-19-related experiences (i.e., time spent with people wearing masks, number of contacts without masks) and recorded children's gaze behavior during emotion labeling. We compared different samples of preschoolers (4.00-5.75 years): The data for the no-COVID-19-experience sample were taken from studies conducted before the pandemic (Adult Faces Task: N = 40; Child Faces Task: N = 30). The data for the with-COVID-19-experience sample (N = 99) were collected during the COVID-19 pandemic in Switzerland between June and November 2021. The results did not indicate differences in children's labeling behavior between the two samples except for fearful adult faces. Children with COVID-19-experience more often labeled fearful faces correctly compared to children with no COVID-19 experience. Furthermore, we found no relations between children's labeling behavior, their individual COVID-19-related experiences, and their gaze behavior. These results suggest that, even though the children had experienced differences in the amount and variability of facial input due to the pandemic, they still received enough input from visible faces to be able to recognize and label different emotions.


Sprint Interval Training and Continuous Aerobic Exercise Training Have Similar Effects on Exercise Motivation and Affective Responses to Exercise in Patients With Major Depressive Disorders: A Randomized Controlled Trial.
Background: Sprint interval training (SIT) has become increasingly popular and is seen as a promising exercise strategy to increase fitness in healthy people. Nevertheless, some scholars doubt the appropriateness of a SIT training protocol for largely physically inactive populations. SIT might be too arduous, and therefore contribute to feelings of incompetence, failure, and lower self-esteem, which may undermine participants' exercise motivation. Therefore, we examined whether participation in 12 SIT sessions would lead to different changes in self-determined motivation, affective responses to exercise, cardiorespiratory fitness, physical activity, and depressive symptom severity compared to aerobic exercise training (CAT) in a sample of patients with major depressive disorders (MDD). Methods: Two groups of 25 patients (39 women, 11 men) with unipolar depression were randomly assigned to the SIT or CAT condition (M = 36.4 years, SD = 11.3). Data were assessed at baseline and post-intervention (three weekly 35-min sessions of SIT/CAT over a 4-week period). Self-determined exercise motivation was assessed with a 12-item self-rating questionnaire, affective valence was assessed in each session, prior, during, and after the exercise training using the Feeling Scale (FS). Cardiovascular fitness was measured with a maximal bicycle ergometer test, self-perceived fitness with a 1-item rating scale, physical activity with the International Physical Activity Questionnaire (IPAQ-SF), and depressive symptom severity with the Beck Depression Inventory II (BDi-II). Results: The SIT and CAT groups did not differ with regard to their changes in self-determined motivation from baseline to post-intervention. Participants in the SIT and CAT group showed similar (positive) affective responses during and after the training sessions. Cardiorespiratory fitness, self-perceived fitness and depressive symptom severity similarly improved in the SIT and CAT group. Finally, significant increases were observed in self-reported physical activity from baseline to post-intervention. However, these increases were larger in the CAT compared to the SIT group. Conclusion: From a motivational point of view, SIT seems just as suited as CAT in the treatment of patients with MDD. This is a promising finding because according to self-determination theory, it seems advantageous for patients to choose between different exercise therapy regimes, and for their preferences with regard to exercise type and intensity to be considered.


Synthesis and luminescent properties of La(1-x)Nd(x)P₅O₁₄ nanocrystals.
La(1-x)Nd(x)P5O14 nanocrystals were synthesized using a coprecipitation method. Their structure and morphology were determined. The luminescence and excitation spectra of La(1-x)Nd(x)P5O14 nanocrystals were measured in the entire range of Nd(3+) concentration. It was found that the relative intensities of absorption transitions increased significantly with concentration due to the cooperative interactions. The effect of concentration on fluorescence transitions was investigated. It was found that the intensity of the (4)F3/2 → (4)I11/2 transition significantly increased with concentration relative to the resonant (4)F3/2 → (4)I9/2 transition almost three times due to strong reabsorption. The concentration quenching of fluorescence was discussed in terms of the Yokota-Tanimoto model.


Effects of synbiotic supplementation on breast milk levels of IgA, TGF-β1, and TGF-β2.
Effects of probiotics on the immunological composition of breast milk have been investigated in a few previous studies. The aims of this study were to determine the effects of synbiotic (probiotic plus prebiotic) supplementation on immunoglobulin A (IgA), transforming growth factor β1 (TGF-β1), and transforming growth factor β2 (TGF-β2) levels of breast milk and on diarrhea incidence in infants. In this randomized, double-blind, and placebo-controlled trial, we recruited 80 lactating mothers who were exclusively breastfeeding their 3-month-old infants. We randomly divided the mothers into 2 groups to receive a daily synbiotic supplement (n = 40) or a placebo (n = 40) for 30 days. Demographic and clinical data (ie, health status) were obtained through an interview. The IgA levels of breast milk were detected by nephelometry, and the levels of TGF-β1 and TGF-β2 were measured using a commercial Platinum ELISA kit. The breast milk IgA increased significantly from 0.41 ± 0.09 to 0.48 ± 0.15 g/L in the supplemented group (P = .018), while in the placebo group, no significant changes were observed. Although the breast milk TGF-β1 levels did not change significantly, the TGF-β2 levels of breast milk increased significantly from 270 ± 37.8 to 382 ± 43.7 pg/mL in the supplemented group (P = .043). Also, the incidence of diarrhea in infants decreased significantly in the supplemented group while no significant changes were observed in the placebo group after the experimental period. Synbiotic supplementation may have positive effects on the immune composition of breast milk and the reduction of diarrhea incidence in infants.


The development of animal personality: relevance, concepts and perspectives.
Recent studies of animal personality have focused on its proximate causation and its ecological and evolutionary significance, but have mostly ignored questions about its development, although an understanding of the latter is highly relevant to these other questions. One possible reason for this neglect is confusion about many of the concepts and terms that are necessary to study the development of animal personality. Here, we provide a framework for studying personality development that focuses on the properties of animal personality, and considers how and why these properties may change over time. We specifically focus on three dimensions of personality: (1) contextual generality at a given age or time, (2) temporal consistency in behavioural traits and in relationships between traits, and (3) the effects of genes and experience on the development of personality at a given age or life stage. We advocate using a new approach, contextual reaction norms, to study the contextual generality of personality traits at the level of groups, individuals and genotypes, show how concepts and terms borrowed from the literature on personality development in humans can be used to study temporal changes in personality at the level of groups and individuals, and demonstrate how classical developmental reaction norms can provide insights into the ways that genes and experiential factors interact across ontogeny to affect the expression of personality traits. In addition, we discuss how correlations between the effects of genes and experience on personality development can arise as a function of individuals' control over their own environment, via niche-picking or niche-construction. Using this framework, we discuss several widely held assumptions about animal personality development that still await validation, identify neglected methodological issues, and describe a number of promising new avenues for future research.


Therapeutic impact of adult-type acute lymphoblastic leukemia regimens in B-cell/L3 acute leukemia and advanced-stage Burkitt's lymphoma.
Adult B/L3-ALL is a rare disease subset characterized by an aggressive clinical course and a poor response to conventional adult ALL-type chemotherapy. Recent data from the GMALL Group showed that prognosis can be improved with an innovative treatment regimen. In the current retrospective survey we focus on therapeutic results obtained at our Institutions during a 15-year period with ALL-type regimens in 34 adults with either B/L3-ALL or advanced-stage Burkitt's lymphoma. Five successive ALL treatment programs were developed. They included a homogeneous induction phase with early intrathecal chemoprophylaxis, multidrug postremission consolidation followed by cranial irradiation (4 trials), high-dose chemotherapy plus autografting (2 trials), late consolidation (2 trials), and variable-length maintenance (4 trials). Early response and prolonged disease-free survival rates were analyzed according to selected clinical and therapeutic variables. Overall, a complete remission was achieved in 62%, with a median duration of 1.6 years and a 10-year remission rate of 49%. A diagnosis of B/L3-ALL (p = 0.007), the use of idarubicin instead of adriamycin during induction (p = 0.018), a serum creatinine < 1.6 mg/dL, and an uninvolved central nervous system were associated with higher response rates. As regards long-term disease-free survival, results were significantly better in patients with < 1 x 10(9)/L L3/blast cells in the peripheral blood (p = 0.0029) and/or aged < 50 years (p = 0.04), and in those consolidated with the most recent rotational high-dose plus peripheral blood stem cell autotransplant regimen. According to the results presented, ALL-like regimens may still represent a worthwhile therapeutic choice. The use of idarubicin during induction, the prognostic subclassification of patients, a careful control of dysmetabolic complications, the selection of the proper chemo-radioprevention for meningeal disease and perhaps the introduction of high-dose chemotherapy supported by autologous stem cell rescue appear to be the mainstay of further improvements.


Diagnostic accuracy of commercially available immunochromatographic rapid tests for diagnosis of dengue in India.
There is limited evidence regarding the accuracy of dengue rapid diagnostic kits despite their extensive use in India. We evaluated the performance of four immunochromatographic Rapid Diagnostic Test (RDTs) kits: Multisure dengue Ab/Ag rapid test (MP biomedicals; MP), Dengucheck combo (Zephyr Biomedicals; ZB), SD bioline dengue duo (Alere; SD) and Dengue day 1 test (J Mitra; JM). This is a laboratory-based diagnostic evaluation study. Rapid tests results were compared to reference non-structural (NS1) antigen or immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) results of 241 dengue-positive samples and 247 dengue-negative samples. Sensitivity and specificity of NS1 and IgM components of each RDT were calculated separately and in combination (either NS1 or IgM positive) against reference standard ELISA. A total of 238, 226, 208, and 146 reference NS1 ELISA samples were tested with MP, ZB, SD, and JM tests, respectively. In comparison to the NS1 ELISA reference tests, the NS1 component of MP, ZB, SD, and JM RDTs demonstrated a sensitivity of 71.8%, 85.1%, 77.2% and 80.9% respectively and specificity of 90.1%, 92.8%, 96.1 %, and 93.6%, respectively. In comparison to the IgM ELISA reference test, the IgM component of RDTs showed a sensitivity of 40.0%, 50.3%, 47.3% and 20.0% respectively and specificity of 92.4%, 88.6%, 96.5%, and 92.2% respectively. Combining NS1 antigen and IgM antibody results led to sensitivities of 87.5%, 82.9%, 93.8% and 91.7% respectively, and specificities of 75.3%, 73.9%, 76.5%, and 80.0% respectively. Though specificities were acceptable, the sensitivities of each test were markedly lower than manufacturers' claims. These results also support the added value of combined antigen-and antibody-based RDTs for the diagnosis of acute dengue.


High-throughput sequencing revealed novel Dehalococcoidia in dechlorinating microbial enrichments from PCB-contaminated marine sediments.
In this study, six PCE-to-ethene dechlorinating cultures, fed with a fermentable substrate (lactate) or hydrogen as electron donor, were obtained from PCB and PCE dechlorinating microcosms constructed with PCB-contaminated marine sediments. A novel Chloroflexi member (OTU-DIS1) affiliated to Dehalococcoidales Incertae Sedis, only distantly related to known dechlorinating bacteria, dominated the enrichment cultures (up to 86% of total OTUs). Sulfate-, thiosulfate- and sulfur-reducing bacteria affiliated to genera Desulfobacter, Dethiosulfatibacter and Desulfuromusa were also found to lesser extent. Remarkably, tceA, vcrA and the bifunctional PCE/PCB dehalogenase genes pcbA1, pcbA4 and pcbA5 were found in all dechlorinating microbial enrichments indicating the coexistence of different Dehalococcoides mccartyi strains. The reductive dechlorination rate in each culture remained unvaried over long-term operation (≈ 30 months) and ranged between 0.85 and 0.97 mmol Cl-1 released L-1 d-1 in the lactate-fed microbial enrichments and between 0.66 and 0.85 mmol Cl-1 released L-1 d-1 in the H2-fed microbial enrichments. Overall, this study highlights the presence of yet unexplored biodiversity in PCBs contaminated marine sediments and indicates these environments as promising sources of novel organohalide-respiring bacteria.


Neuroimaging studies of normal brain development and their relevance for understanding childhood neuropsychiatric disorders.
To review the maturational events that occur during prenatal and postnatal brain development and to present neuroimaging findings from studies of healthy individuals that identify the trajectories of normal brain development. Histological and postmortem findings of early brain development are presented, followed by a discussion of anatomical, diffusion tensor, proton spectroscopy, and functional imaging findings from studies of healthy individuals, with special emphasis on longitudinal data. Early brain development occurs through a sequence of major events, beginning with the formation of the neural tube and ending with myelination. Brain development at a macroscopic level typically proceeds first in sensorimotor areas, spreading subsequently and progressively into dorsal and parietal, superior temporal, and dorsolateral prefrontal cortices throughout later childhood and adolescence. These patterns of anatomical development parallel increasing activity in frontal cortices that subserves the development of higher-order cognitive functions during late childhood and adolescence. Disturbances in these developmental patterns seem to be involved centrally in the pathogenesis of various childhood psychiatric disorders including childhood-onset schizophrenia, attention-deficit/hyperactivity disorder, developmental dyslexia, Tourette's syndrome, and bipolar disorder. Advances in imaging techniques have enhanced our understanding of normal developmental trajectories in the brain, which may improve insight into the abnormal patterns of development in various childhood psychiatric disorders.


Algal Proteins: Extraction, Application, and Challenges Concerning Production.
Population growth combined with increasingly limited resources of arable land and fresh water has resulted in a need for alternative protein sources. Macroalgae (seaweed) and microalgae are examples of under-exploited "crops". Algae do not compete with traditional food crops for space and resources. This review details the characteristics of commonly consumed algae, as well as their potential for use as a protein source based on their protein quality, amino acid composition, and digestibility. Protein extraction methods applied to algae to date, including enzymatic hydrolysis, physical processes, and chemical extraction and novel methods such as ultrasound-assisted extraction, pulsed electric field, and microwave-assisted extraction are discussed. Moreover, existing protein enrichment methods used in the dairy industry and the potential of these methods to generate high value ingredients from algae, such as bioactive peptides and functional ingredients are discussed. Applications of algae in human nutrition, animal feed, and aquaculture are examined.


Incidentally Diagnosed Anomalous Right Coronary Artery with an Interarterial Course Presenting as Chest Pain.
The frequency of advanced cardiopulmonary imaging has increased the incidence of diagnosis of coronary artery anomalies, but this poses an interesting management dilemma of what to do with them once these anomalies are found. We present the case of a 57-year-old female with a past medical history of postpartum cardiomyopathy, recovered heart failure with reduced ejection fraction (EF), and alcohol use disorder who presented with chest pain, shortness of breath, nausea, vomiting, and palpitations. A CT angiogram was performed to rule out pulmonary embolism. No pulmonary embolism was found; however, the CT scan revealed an anomalous right coronary artery originating from the left coronary cusp, which had a malignant interarterial course (ARCA-LCC-IA) with a right dominant pattern of myocardial circulation. Subsequent nuclear stress testing did not show evidence of ischemia. Echocardiogram revealed a recurrently reduced EF of 40%. Our patient poses a management dilemma since she presented with possible angina and was found to have an anomalous right coronary artery (ARCA) with a malignant course, but subsequently she had a negative exercise stress test with nuclear perfusion imaging. We will review the literature on ARCA-LCC-IA and its clinical manifestations both generally and with its connection to this case as well as its management. We discuss the incidence, diagnosis, and management of ARCA-LCC-IA, with a focus on incidentally found lesions.


Spinal substance P receptor expression and internalization in acute, short-term, and long-term inflammatory pain states.
Inflammatory pain involves the sensitization of both primary afferent and spinal cord neurons. To explore the neurochemical changes that contribute to inflammatory pain, we have examined the expression and ligand-induced internalization of the substance P receptor (SPR) in the spinal cord in acute, short-term, and long-term inflammatory pain states. These inflammatory models included unilateral injection of formalin (8-60 min), carrageenan (3 hr), and complete Freund's adjuvant (CFA; 3 d) into the rat hindpaw as well as adjuvant-induced polyarthritis (21 d). In acute inflammatory pain there is ongoing release of substance P (SP) as measured by SPR internalization in lamina I neurons at both 8 and 60 min after formalin injection. Although there is no tonic release of SP in short-term inflammatory pain, at 3 hr after carrageenan injection, SP is released in response to both noxious and non-noxious somatosensory stimulation with SPR internalization being observed in neurons located in both laminae I and III-IV. In long-term inflammatory pain models (CFA and polyarthritis) the same pattern of SP release and SPR activation occurs as is observed in short-term inflammation with the addition that there is a significant upregulation of the SPR in lamina I neurons. These results suggest that SPR internalization might serve as a marker of the contribution of ongoing primary afferent input in acute and persistent pain states. These stereotypical neurochemical changes suggest that there are unique neurochemical signatures for acute, short-term, and long-term inflammatory pain.


An Antennae-Enriched Odorant-Binding Protein EonuOBP43 Mediate the Behavioral Response of the Tea Green Leafhopper, Empoasca onukii Matsuda to the Host and Nonhost Volatiles.
Olfaction is crucial for Empoasca onukii Matsuda to recognize odors from the host and nonhost plants, and it has been proposed that odorant binding proteins are directly required for odorant discrimination and represent potential targets of interest for pest control. Here, we cloned EonuOBP43 and expressed the recombinant EonuOBP43 protein. Furthermore, competitive fluorescence binding assays with 19 ligands indicated that terpenoids and alkanes showed a relatively higher than for other classes of chemicals. Additionally, ligand docking and site-directed mutagenesis results revealed that seven hydrophobic residues, including Val-86, Met-89, Phe-90, Ile-104, Ile-105, Leu-130, and Val-134, played a key role in the binding of EonuOBP43 to plant volatiles. In olfactometer tests, E. onukii were significantly attracted to α-farnesene and repelled to β-caryophyllene, and dsOBP43 treated adult lost response to α-farnesene and β-caryophyllene. In summary, our results demonstrated that EonuOBP43 may function as a carrier in the process of sensing plant compounds of E. onukii.


On the functionality of the visually deprived occipital cortex in early blind persons.
In early blind mammals, the deprived visual cortex undergoes anatomical and functional alterations. Its functional role was investigated in the early human blind by using patterns of cortical activation as measured by scalp-recorded event-related slow negative DC potential shifts. The blind showed higher occipital negativity than did sighted persons both during a tactile reading task and a non-reading tactile control task. Results point to a possible role for the blind's visual cortex in tactile processes.


Association of Adolescent Sport Participation With Cognition and Depressive Symptoms in Early Adulthood.
Recent studies have associated sport-related concussion with depression and impaired cognitive ability later in life in former professional football players. However, population studies with two 1950s-era cohorts did not find an association between high school football participation and impaired cognition or depressive symptoms in late adulthood. This study assessed whether actual/intended participation in contact sports during adolescence had an adverse effect on participants' cognition or depressive symptoms in early adulthood. We hypothesized that there would not be an association. Cohort study; Level of evidence, 2. This study used a subsample (n = 10,951) from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally (United States) representative prospective cohort study following participants through 4 waves of data collection from 1994 through 2008. Participants were categorized as actual/intended participation in no sports, noncontact sports only, and contact sports. We constructed 6 multivariate and logistic regression models predicting word recall, number recall, modified Center for Epidemiologic Studies Depression Scale, depression diagnosis, suicide ideation, and suicide attempts at wave IV as a function of sport participation during wave I. Sport participation was treated as a factor with the referent category noncontact sports. This analysis was repeated on a males-only sample (n = 5008). In the males-only analysis, participants were classified as actual/intended participation in no sports, noncontact sports, contact sports other than American football, and American football. The referent category remained noncontact sports. Intention to participate in contact sports was not significantly associated with any of the outcomes in the full-sample analysis. Intention to participate in football was significantly associated with a reduced odds of depression diagnosis in adulthood (odds ratio, 0.70; P = .02) when compared with noncontact sports participation in the males-only sample. Football was not significantly associated with impaired cognitive ability, increased depressive symptoms, or increased suicide ideation. Actual/intended participation in contact sports during adolescence did not adversely affect Add Health participants' cognition or depressive symptoms in young adulthood.


Anxiety Sensitivity and Fast-Food Ordering Habits Among Black Adults.
Black adults experience high rates of overweight/obesity, which is linked to chronic diseases and is exacerbated by fast-food consumption. Anxiety sensitivity, a relative stable fear of anxiety-related sensations, has been linked to high caloric intake. Here, we examine whether anxiety sensitivity is associated with fast-food ordering habits within a convenience sample of Black adults. Of 124 adults (79.4% women; Mage=49.3±11.6; 84.8% overweight/obese), 107 (86.3%) reported eating from a fast-food restaurant in the last month. Participants completed the Anxiety Sensitivity-Index 3, which has a total score and physical, cognitive, and social concerns subscales. Investigator-generated items queried frequency of ordering "supersized" quantities of fast-food (e.g., cheeseburgers, fries), and healthy items (e.g., salads, oatmeal, yogurt), respectively, from "never" to "always." Covariate-adjusted ordinal logistic regression models were used to assess relations between measures of interest. Anxiety sensitivity (total and physical concerns) was associated with greater odds of more frequently ordering supersized unhealthy fast-food; and anxiety sensitivity (total and cognitive concerns) was associated with lower odds of more frequently ordering healthy items from fast-food restaurants. Results suggest that adults with greater anxiety sensitivity may engage in fast-food ordering habits that can contribute to the overweight/obesity epidemic. Future studies should replicate results and determine the potential for anxiety sensitivity-reduction interventions to affect dietary choices that contribute to overweight/obesity.


Critical assessment of approaches for molecular docking to elucidate associations of HLA alleles with adverse drug reactions.
Adverse drug reactions have been linked with genetic polymorphisms in HLA genes in numerous different studies. HLA proteins have an essential role in the presentation of self and non-self peptides, as part of the adaptive immune response. Amongst the associated drugs-allele combinations, anti-HIV drug Abacavir has been shown to be associated with the HLA-B*57:01 allele, and anti-epilepsy drug Carbamazepine with B*15:02, in both cases likely following the altered peptide repertoire model of interaction. Under this model, the drug binds directly to the antigen presentation region, causing different self peptides to be presented, which trigger an unwanted immune response. There is growing interest in searching for evidence supporting this model for other ADRs using bioinformatics techniques. In this study, in silico docking was used to assess the utility and reliability of well-known docking programs when addressing these challenging HLA-drug situations. The overall aim was to address the uncertainty of docking programs giving different results by completing a detailed comparative study of docking software, grounded in the MHC-ligand experimental structural data - for Abacavir and to a lesser extent Carbamazepine - in order to assess their performance. Four docking programs: SwissDock, ROSIE, AutoDock Vina and AutoDockFR, were used to investigate if each software could accurately dock the Abacavir back into the crystal structure for the protein arising from the known risk allele, and if they were able to distinguish between the HLA-associated and non-HLA-associated (control) alleles. The impact of using homology models on the docking performance and how using different parameters, such as including receptor flexibility, affected the docking performance were also investigated to simulate the approach where a crystal structure for a given HLA allele may be unavailable. The programs that were best able to predict the binding position of Abacavir were then used to recreate the docking seen for Carbamazepine with B*15:02 and controls alleles. It was found that the programs investigated were sometimes able to correctly predict the binding mode of Abacavir with B*57:01 but not always. Each of the software packages that were assessed could predict the binding of Abacavir and Carbamazepine within the correct sub-pocket and, with the exception of ROSIE, was able to correctly distinguish between risk and control alleles. We found that docking to homology models could produce poorer quality predictions, especially when sequence differences impact the architecture of predicted binding pockets. Caution must therefore be used as inaccurate structures may lead to erroneous docking predictions. Incorporating receptor flexibility was found to negatively affect the docking performance for the examples investigated. Taken together, our findings help characterise the potential but also the limitations of computational prediction of drug-HLA interactions. These docking techniques should therefore always be used with care and alongside other methods of investigation, in order to be able to draw strong conclusions from the given results.


Differential expression of HLA-DQ alleles in peripheral blood mononuclear cells: alleles associated with susceptibility to and protection from autoimmune type 1 diabetes.
Differential expression of human leucocyte antigen (HLA) class II genes has been postulated to influence the risk of developing autoimmune disease. In this study, we investigated the relationship between the level of mRNA expression of DQA1 and DQB1 alleles in peripheral blood mononuclear cells and the influence of the alleles on susceptibility to type 1 diabetes (T1D). Transcripts from pairs of DQA1 and DQB1 alleles were quantified in 59 DQ-heterozygous individuals (29 patients with T1D and 30 healthy control subjects). Luciferase reporter gene assays were used to investigate the relative promoter activities of the alleles associated with high and low risk of disease. DQA1*0301 and the DQB1*06 group of alleles (*0601, *0602, *0603 and *0604) were generally overexpressed in comparison to other alleles. In contrast, mRNA for DQB1*0201/*0202 was generally less abundant than other DQB1 transcripts. These data correlated well with the relative promoter activities observed for the diabetes-associated alleles; the strongest promoters were those derived from DQA1*0301 and DQB1*0602, while a 700-bp fragment derived from the DQB1*0201 promoter showed the lowest activity of the DQB1 constructs. There was no simple correlation between the level of expression of specific DQ alleles and their influence on the risk of diabetes. The functional relevance of our findings and their implications for the pathogenesis of autoimmunity remain to be determined.


Early synaptic dysfunction induced by α-synuclein in a rat model of Parkinson's disease.
Evidence suggests that synapses are affected first in Parkinson's disease (PD). Here, we tested the claim that pathological accumulation of α-synuclein, and subsequent synaptic disruption, occur in absence of dopaminergic neuron loss in PD. We determined early synaptic changes in rats that overexpress human α-synuclein by local injection of viral-vectors in midbrain. We aimed to achieve α-synuclein levels sufficient to induce terminal pathology without significant loss of nigral neurons. We tested synaptic disruption in vivo by analyzing motor defects and binding of a positron emission tomography (PET) radioligand to the vesicular monoamine transporter 2, (VMAT2), [11C]dihydrotetrabenazine (DTBZ). Animals overexpressing α-synuclein had progressive motor impairment and, 12 weeks post-surgery, showed asymmetric in vivo striatal DTBZ binding. The PET images matched ligand binding in post-mortem tissue, and histological markers of dopaminergic integrity. Histology confirmed the absence of nigral cell death with concomitant significant loss of striatal terminals. Progressive aggregation of proteinase-K resistant and Ser129-phosphorylated α-synuclein was observed in dopaminergic terminals, in dystrophic swellings that resembled axonal spheroids and contained mitochondria and vesicular proteins. In conclusion, pathological α-synuclein in nigro-striatal axonal terminals leads to early axonal pathology, synaptic disruption, dysfunction of dopaminergic neurotransmission, motor impairment, and measurable change of VMAT2 in the absence of cell loss.