Diagnostic laparoscopy in abdominal stab wounds: a prospective, randomized study.
The optimal strategy for identifying patients with abdominal stab wounds requiring surgical repair has not been defined. The potential benefits of diagnostic laparoscopy by incorporating it into the routine diagnostic workup of patients with anterior abdominal stab wounds was evaluated in a two-layer, randomized study. From May 1997 through January 2002, stable patients without peritonitis but with demonstrated peritoneal violation were randomized (A) to exploratory laparotomy (AEL) (n = 23) or diagnostic laparoscopy (ADL) (n = 20). Simultaneously, patients with equivocal peritoneal violation on local wound exploration were randomized (B) to diagnostic laparoscopy (BDL) (n = 28) or expectant nonoperative management (BNOM) (n = 31). Hospital morbidity, length of stay, and costs were primary endpoints, with postdischarge disability being a secondary endpoint. In patients with peritoneal penetration (AEL vs. ADL), there were minimal differences in the therapeutic operation rate (8 of 23 [AEL] vs. 8 of 20 [ADL], p = 0.761), mortality (none), morbidity (3 of 23 vs. 2 of 20, p = 0.999), hospital stay (mean +/- SD) (5.7 +/- 2.5 vs. 5.1 +/- 4.0 days, p = 0.049), hospital costs (4.6 +/- 1.3 vs. 4.8 +/- 1.9 x 1,000 EUR, p = 0.576), and length of sick leave (34 +/- 12 vs. 29 +/- 11 days, p = 0.305). In patients with equivocal peritoneal penetration (BDL vs. BNOM), laparoscopy found more mostly minor organ injuries (7 of 28 [BDL] vs. 1 of 31 [BNOM], p = 0.022) with no significant difference in therapeutic operations (3 of 28 vs. 1 of 31, p = 0.337) or morbidity (3 of 28 vs. 0 of 31, p = 0.101), but was associated with increased length of stay (2.6 +/- 2.1 vs. 1.9 +/- 1.8 days, p = 0.022), hospital costs (4.2 +/- 1.3 vs. 1.5 +/- 1.1 x 1,000 EUR, p = 0.000), and sick leave requirements (18 of 23 vs. 8 of 28 of eligible patients, p = 0.001). In patients with demonstrated peritoneal violation, laparoscopy offers little benefit over exploratory laparotomy. In patients with equivocal peritoneal penetration on local wound exploration, laparoscopy detects more mostly minor organ injuries than expectant nonoperative management but is associated with increased hospital stay, costs, and sick leave requirements. Overall, diagnostic laparoscopy cannot be recommended as a routine diagnostic tool in anterolateral abdominal and thoracoabdominal stab wounds.


The glucose-regulated protein GRP94 interacts avidly in the endoplasmic reticulum with sucrase-isomaltase isoforms that are associated with congenital sucrase-isomaltase deficiency.
The glucose-regulated protein GRP94 is a molecular chaperone that is located in the endoplasmic reticulum (ER). Here, we demonstrate in pull down experiments an interaction between GRP94 and sucrase-isomaltase (SI), the most prominent disaccharidase of the small intestine. GRP94 binds to SI exclusively via its mannose-rich form compatible with an interaction occurring in the ER. We have also examined the interaction GRP94 to a panel of SI mutants that are associated with congenital sucrase-isomaltase deficiency (CSID). These mutants exhibited more efficient binding to GRP94 than wild type SI underlining a specific role of this chaperone in the quality control in the ER. In view of the hypoxic milieu of the intestine, we probed the interaction of GRP94 to SI and its mutants in cell culture under hypoxic conditions and observed a substantial increase in the binding of GRP94 to the SI mutants. The interaction of GRP94 to the major carbohydrate digesting enzyme and regulating its folding as well as retaining SI mutants in the ER points to a potential role of GRP94 in maintenance of intestinal homeostasis by chaperoning and stabilizing SI.


Evaluation of Wait Times for Otolaryngology Appointments in Illinois.
The objective of this study was to quantify the wait times that patients may encounter for common clinical diagnoses when seeking otolaryngology care, while determining whether a wait time disparity exists based on geographic location within Illinois. In November 2022, a list of Illinois otolaryngologists was obtained from www.entnet.org. Using a uniform script, each of the 291 otolaryngologists were contacted. The caller posed as a new patient with either sudden sensorineural hearing loss, a neck mass, or chronic sinusitis. Each clinic was called 3 times and wait times were recorded. One hundred fifty-eight otolaryngologists were included in the analysis. The average statewide wait time for a new patient presenting with sudden unilateral hearing loss, a neck mass, and chronic sinusitis was 18.0, 22.6, and 25.5 days, respectively. There was no statistically significant difference between urban and rural wait times. Although wait time differences were noted, the lack of urban versus rural p value significance may be attributed to the small sample size (n = 11) of rural otolaryngologists in Illinois. However, the overall wait times in this study were longer compared to those reported in other studies, suggesting that the current number of otolaryngologists in Illinois is inadequate to meet the public need. We have demonstrated that the current demand for otolaryngology care is outstripping the existing supply in Illinois. This suggests that an emphasis should be placed on training more otolaryngologists, or increasing the use of physician extenders, while incentivizing otolaryngologists to practice in rural areas. 5.


Improved active fiber-based retroreflector with intensity stabilization and a polarization monitor for the near UV.
We present an improved active fiber-based retroreflector (AFR) providing high-quality wavefront-retracing anti-parallel laser beams in the near UV. We use our improved AFR for first-order Doppler-shift suppression in precision spectroscopy of atomic hydrogen, but our setup can be adapted to other applications where wavefront-retracing beams with defined laser polarization are important. We demonstrate how weak aberrations produced by the fiber collimator may remain unobserved in the intensity of the collimated beam but limit the performance of the AFR. Our general results on characterizing these aberrations with a caustic measurement can be applied to any system where a collimated high-quality laser beam is required. Extending the collimator design process by wave optics propagation tools, we achieved a four-lens collimator for the wavelength range 380-486 nm with the beam quality factor of M2 ≃ 1.02, limited only by the not exactly Gaussian beam profile from the single-mode fiber. Furthermore, we implemented precise fiber-collimator alignment and improved the collimation control by combining a precision motor with a piezo actuator. Moreover, we stabilized the intensity of the wavefront-retracing beams and added in-situ monitoring of polarization from polarimetry of the retroreflected light.


Discovery of a general method of solving the Schrödinger and dirac equations that opens a way to accurately predictive quantum chemistry.
Just as Newtonian law governs classical physics, the Schrödinger equation (SE) and the relativistic Dirac equation (DE) rule the world of chemistry. So, if we can solve these equations accurately, we can use computation to predict chemistry precisely. However, for approximately 80 years after the discovery of these equations, chemists believed that they could not solve SE and DE for atoms and molecules that included many electrons. This Account reviews ideas developed over the past decade to further the goal of predictive quantum chemistry. Between 2000 and 2005, I discovered a general method of solving the SE and DE accurately. As a first inspiration, I formulated the structure of the exact wave function of the SE in a compact mathematical form. The explicit inclusion of the exact wave function's structure within the variational space allows for the calculation of the exact wave function as a solution of the variational method. Although this process sounds almost impossible, it is indeed possible, and I have published several formulations and applied them to solve the full configuration interaction (CI) with a very small number of variables. However, when I examined analytical solutions for atoms and molecules, the Hamiltonian integrals in their secular equations diverged. This singularity problem occurred in all atoms and molecules because it originates from the singularity of the Coulomb potential in their Hamiltonians. To overcome this problem, I first introduced the inverse SE and then the scaled SE. The latter simpler idea led to immediate and surprisingly accurate solution for the SEs of the hydrogen atom, helium atom, and hydrogen molecule. The free complement (FC) method, also called the free iterative CI (free ICI) method, was efficient for solving the SEs. In the FC method, the basis functions that span the exact wave function are produced by the Hamiltonian of the system and the zeroth-order wave function. These basis functions are called complement functions because they are the elements of the complete functions for the system under consideration. We extended this idea to solve the relativistic DE and applied it to the hydrogen and helium atoms, without observing any problems such as variational collapse. Thereafter, we obtained very accurate solutions of the SE for the ground and excited states of the Born-Oppenheimer (BO) and non-BO states of very small systems like He, H(2)(+), H(2), and their analogues. For larger systems, however, the overlap and Hamiltonian integrals over the complement functions are not always known mathematically (integration difficulty); therefore we formulated the local SE (LSE) method as an integral-free method. Without any integration, the LSE method gave fairly accurate energies and wave functions for small atoms and molecules. We also calculated continuous potential curves of the ground and excited states of small diatomic molecules by introducing the transferable local sampling method. Although the FC-LSE method is simple, the achievement of chemical accuracy in the absolute energy of larger systems remains time-consuming. The development of more efficient methods for the calculations of ordinary molecules would allow researchers to make these calculations more easily.


The effect of early weight-bearing on the stability of femoral neck fractures treated with Knowles pins.
I compared the effects of early weight-bearing on the stability of femoral neck fractures following Knowles-pin fixation with data on a similar group of patients who were studied ten years previously, in which weight-bearing had been delayed until radiographic evidence of fracture-healing was apparent. The results concerning stability were essentially comparable, indicating that early weight-bearing did not adversely affect the stability of a properly reduced and pinned displaced fracture of the femoral neck. Factors that did adversely affect stability following fixation with Knowles pins included the degree of initial displacement of the fracture (Garden Type IV), failure to adequately reduce or fix the fracture, and severe demineralizing bone disease as measured in an iliac-crest biopsy specimen obtained at the time of surgery.


The Impact of Missing Values and Single Imputation upon Rasch Analysis Outcomes: A Simulation Study.
Imputation becomes common practice through availability of easy-to-use algorithms and software. This study aims to determine if different imputation strategies are robust to the extent and type of missingness, local item dependencies (LID), differential item functioning (DIF), and misfit when doing a Rasch analysis. Four samples were simulated and represented a sample with good metric properties, a sample with LID, a sample with DIF, and a sample with LID and DIF. Missing values were generated with increasing proportion and were either missing at random or completely at random. Four imputation techniques were applied before Rasch analysis and deviation of the results and the quality of fit compared. Imputation strategies showed good performance with less than 15% of missingness. The analysis with missing values performed best in recovering statistical estimates. The best strategy, when doing a Rasch analysis, is the analysis with missing values. If for some reason imputation is necessary, we recommend using the expectation-maximization algorithm.


Trypsin inhibitory capacity in vernal keratoconjunctivitis.
To study tear trypsin inhibitory capacity (T-TIC), serum trypsin inhibitory capacity (S-TIC) and their relationship to matrix metalloproteinases (MMP)-1 and -9 in patients with vernal keratoconjunctivitis (VKC). In the first phase of the study, inactivation of alpha-1 antitrypsin (AAT) by MMP-1 and -9 was investigated in vitro. Subsequently, tear samples were collected after clinical evaluation from 14 patients with active VKC and 15 normal control subjects. Tear cytology was performed on all samples. Levels of T-TIC and S-TIC were determined by spectrophotometry, whereas levels of tear pro-MMP-1, pro-MMP-9, and active MMP-1 and -9 were determined by enzyme-linked immunosorbent assay (ELISA). MMP-1 and -9 inactivated AAT in vitro. S-TIC was significantly higher (P < 0.0001), and T-TIC (P < 0.0001) significantly lower in VKC samples. Tear levels of pro-MMP-1 and pro-MMP-9, and the activity of MMP-1 and -9 was significantly greater in patients with VKC than in healthy subjects (P < 0.0001). There was no significant correlation between T-TIC, MMP-1, and MMP-9 activity. In addition, T-TIC was not correlated to the total clinical score or to single clinical sign scores. In this study, tear trypsin inhibitory capacity was shown to be reduced and tear MMP-1 and -9 activity increased in patients with VKC. Although T-TIC did not correlate with VKC severity, a local reduced inhibitory capacity of ATT may facilitate or prolong conjunctival inflammation in VKC.


Endoscopic-assisted combined transcrusal anterior petrosal approach for resection of large petroclival meningioma: operative video and nuances of technique.
In this illustrative video, the authors demonstrate an endoscopic-assisted combined transcrusal anterior petrosal approach for resection of a large petroclival meningioma with significant brainstem compression involving Meckel's cave. This unique petrosal variant provides increased petroclival exposure that can potentially preserve hearing by combining a transcrusal labyrinthectomy with anterior petrosectomy (Kawase's approach). The advantages include multidirectional angles of attack to the brainstem and petroclival region without cerebellar retraction. Endoscopic assistance allows expanded visualization into deep surgical corridors. The surgery was performed in a two-stage fashion, and a near-total resection was achieved with cranial nerve and hearing preservation. The operative nuances are demonstrated. The video can be found here: https://stream.cadmore.media/r10.3171/2022.1.FOCVID21257.


Zombie states for description of structure and dynamics of multi-electron systems.
Canonical Coherent States (CSs) of Harmonic Oscillator have been extensively used as a basis in a number of computational methods of quantum dynamics. However, generalising such techniques for fermionic systems is difficult because Fermionic Coherent States (FCSs) require complicated algebra of Grassmann numbers not well suited for numerical calculations. This paper introduces a coherent antisymmetrised superposition of "dead" and "alive" electronic states called here Zombie State (ZS), which can be used in a manner of FCSs but without Grassmann algebra. Instead, for Zombie States, a very simple sign-changing rule is used in the definition of creation and annihilation operators. Then, calculation of electronic structure Hamiltonian matrix elements between two ZSs becomes very simple and a straightforward technique for time propagation of fermionic wave functions can be developed. By analogy with the existing methods based on Canonical Coherent States of Harmonic Oscillator, fermionic wave functions can be propagated using a set of randomly selected Zombie States as a basis. As a proof of principles, the proposed Coupled Zombie States approach is tested on a simple example showing that the technique is exact.


Predicting protein thermostability changes from sequence upon multiple mutations.
A basic question in protein science is to which extent mutations affect protein thermostability. This knowledge would be particularly relevant for engineering thermostable enzymes. In several experimental approaches, this issue has been serendipitously addressed. It would be therefore convenient providing a computational method that predicts when a given protein mutant is more thermostable than its corresponding wild-type. We present a new method based on support vector machines that is able to predict whether a set of mutations (including insertion and deletions) can enhance the thermostability of a given protein sequence. When trained and tested on a redundancy-reduced dataset, our predictor achieves 88% accuracy and a correlation coefficient equal to 0.75. Our predictor also correctly classifies 12 out of 14 experimentally characterized protein mutants with enhanced thermostability. Finally, it correctly detects all the 11 mutated proteins whose increase in stability temperature is >10 degrees C. The dataset and the list of protein clusters adopted for the SVM cross-validation are available at the web site http://lipid.biocomp.unibo.it/~ludovica/thermo-meso-MUT.


[Effects in the adherence treatment and psychological adjustment after the disclosure of HIV/AIDS diagnosis with the "DIRE" clinical model in Colombian children under 17].
A study in five Colombian cities in 2006, confirms the findings of other international studies: the majority of HIV-positive children not know their diagnosis, caregivers are reluctant to give this information because they believe that the news will cause emotional distress to the child becoming primary purpose of this study to validate a model of revelation. We implemented a clinical model, referred to as: "DIRE" that hypothetically had normalizing effects on psychological adjustment and adherence to antiretroviral treatment of HIV seropositive children, using a quasi-experimental design. Test were administered (questionnaire to assess patterns of disclosure and non-disclosure of the diagnosis of VIH/SIDA on children in health professionals and participants caregivers, Family Apgar, EuroQol EQ- 5D, MOS Social Support Survey Questionnaire Information treatment for VIH/SIDA and child Symptom Checklist CBCL/6-18 adapted to Latinos) before and after implementation of the model to 31 children (n: 31), 30 caregivers (n: 30) and 41 health professionals. Data processing was performed using the Statistical Package for the Social Science version 21 by applying parametric tests (Friedman) and nonparametric (t Student). No significant differences in adherence to treatment (p=0.392), in the psychological adjustment were found positive significant differences at follow-ups compared to baseline 2 weeks (p: 0.001), 3 months (p: 0.000) and 6 months (p: 0.000). The clinical model demonstrated effectiveness in normalizing of psychological adjustment and maintaining treatment compliance. The process also generated confidence in caregivers and health professionals in this difficult task.


Analysis of antigenic variation in cysticerci of Taenia solium.
By studying the reactions and cross-reactions of antigen extracts from different collections of Taenia solium with their respective hyperimmune antisera, and by using numerical taxonomy to analyze the results, a measure of antigenic diversification within T. solium was established. Results varied somewhat depending on the immunological method employed. Double immunodiffusion and immunoelectrophoresis agreed in that all cysticerci were not identical, but shared approximately one third of their antigens. Double immunodiffusion recognized two groups of identical cysticerci: one included 50% of the cysticerci and the other, 21%. Immunoelectrophoresis was more discriminatory in that it recognized few extracts as identical. Electrophoretic data revealed that the most frequently shared antigen among cysticerci corresponded to that most frequently detected by immunologically responsive humans with cerebral cysticercosis. Antigen diversification of T. solium may provide a possible explanation of the pleomorphic immune response of man to this parasite.U


A Review of the Role of Bioreactors for iPSCs-Based Tissue-Engineered Articular Cartilage.
Osteoarthritis (OA) is the most common degenerative joint disease without an ultimate treatment. In a search for novel approaches, tissue engineering (TE) has shown great potential to be an effective way for hyaline cartilage regeneration and repair in advanced stages of OA. Recently, induced pluripotent stem cells (iPSCs) have been appointed to be essential stem cells for degenerative disease treatment because they allow a personalized medicine approach. For clinical translation, bioreactors in combination with iPSCs-engineerd cartilage could match patients needs, serve as platform for large-scale patient specific cartilage production, and be a tool for patient OA modelling and drug screening. Furthermore, to minimize in vivo experiments and improve cell differentiation and cartilage extracellular matrix (ECM) deposition, TE combines existing approaches with bioreactors. This review summarizes the current understanding of bioreactors and the necessary parameters when they are intended for cartilage TE, focusing on the potential use of iPSCs. Bioreactors intended for cartilage TE must resemble the joint cavity niche. However, recreating human synovial joints is not trivial because the interactions between various stimuli are not entirely understood. The use of mechanical and electrical stimulation to differentiate iPSCs, and maintain and test chondrocytes are key stimuli influencing hyaline cartilage homeostasis. Incorporating these stimuli to bioreactors can positively impact cartilage TE approaches and their possibility for posterior translation into the clinics.


Transmastoid approach to spontaneous temporal bone cerebrospinal fluid leaks: hearing improvement and success of repair.
To determine whether the transmastoid approach to repair of spontaneous temporal bone cerebrospinal fluid (CSF) leak is safe and effective and if improvement in conductive hearing loss is an achievable goal with this approach. Case series with chart review. Tertiary academic medical center. Fifteen consecutive patients (16 ears) presented with spontaneous temporal bone CSF leaks over a 6-year period. Clinical data, imaging, audiometry, operative reports, and postoperative course were reviewed. Median age was 59.5 years. Mean body mass index was 40.7 kg/m2. All presented with chronic otorrhea after tympanostomy tube placement and conductive/mixed hearing loss. The mean preoperative air-bone gap was 19 dB. A transmastoid approach alone was used in 15 cases; 1 underwent middle fossa craniotomy. Most defects were located in the tegmen mastoideum and tympani. All repairs were multilayered, typically using autologous mastoid bone, temporalis fascia, and tissue sealant. Primary repair was successful in 15 cases; 1 patient with persistent postoperative otorrhea subsequently underwent middle fossa craniotomy, but no frank leakage was found. No serious complications were encountered. Following transmastoid repair, postoperative audiograms were available for 14 patients. The mean improvement in air-bone gap was 12 dB. Closure of the air-bone gap to ≤12 dB occurred in 100% of cases. The transmastoid approach to repair of spontaneous temporal bone CSF leak is highly successful. Furthermore, patients in this series had excellent hearing results with closure of their air-bone gap to ≤12 dB, which has not been previously described.


[Analysis on the scrap situation of COVID-19 vaccine in Suzhou city].
To analyze the usage and loss of the COVID-19 vaccine in ten districts of Suzhou city from December 18, 2020 to April 30, 2021.The results showed the loss rate was 0.222‰ in Suzhou city. The loss rate of pre-filled packaging COVID-19 vaccine was higher than that of vial packaging. The loss rate of 40 packaging was the lowest in vial packaging. The loss rate of all kinds of COVID-19 vaccine in stable inoculation unit was the lowest. It is recommended to distribute 40 vial packaging COVID-19 vaccine for centralized vaccination to reduce the loss of COVID-19 vaccine.


Contemporary Outcomes of Infants with Gastroschisis in North America: A Multicenter Cohort Study.
To quantify outcomes and analyze factors predictive of morbidity and mortality in infants with gastroschisis. Clinical data regarding neonates with gastroschisis born between 2009 and 2014 were prospectively collected at 175 North American centers. Multivariate regression was used to assess risk factors for mortality and length of stay (LOS). Gastroschisis was diagnosed in 4420 neonates with median birth weight 2410 g (IQR 2105-2747). Survival (discharge home or alive in hospital at 1 year) was 97.8% with a 37 day median LOS (IQR 27-59). Sepsis, defined by positive blood or cerebrospinal fluid culture, was the only significant independent predictor of mortality (P = .04). Significant independent determinants of LOS and the percentage of neonates affected were as follows: bowel resection (9.8%, P < .0001), sepsis (8.6%, P < .0001), presence of other congenital anomalies (7.6%, including 5.8% with intestinal atresias, P < .0001), necrotizing enterocolitis (4.5%, P < .0001), and small for gestational age (37.3%, P = .0006). Abdominal surgery in addition to gastroschisis repair occurred in 22.3%, with 6.4% receiving gastrostomy or jejunostomy tubes and 6.3% requiring ostomy creation. At discharge, 57.0% were less than the 10th percentile weight for age. The mode of delivery (52.4% cesarean delivery) was not associated with any differences in outcome. Although neonates with gastroschisis have excellent overall survival they remain at risk for death from sepsis, prolonged hospitalization, multiple abdominal operations, and malnutrition at discharge. Outcomes appear unaffected by the use of cesarean delivery. Further opportunities for quality improvement include sepsis prevention and enhanced nutritional support.


Management of oncologic transplant recipient: the profile of the radiation oncologist.
Long-term survival after organ transplantation is increasing. As a result, many physicians may encounter various solid organ cancers during follow up. We review papers who address their attention on those malignancies and their treatment. Aim of this work is to discuss the role of radiotherapy especially when helped by new technologies in the management of brain, skin, head and neck, lung, breast, prostate and anal cancer. In our institution we are used to treat such patients by Helical Tomotherapy in order to avoid graft and to limit high risk toxicity. As example, we include a scalp and pelvic irradiation in which high dose conformality is linked to best organ sparing.


The physics of bacterial decision making.
The choice that bacteria make between sporulation and competence when subjected to stress provides a prototypical example of collective cell fate determination that is stochastic on the individual cell level, yet predictable (deterministic) on the population level. This collective decision is performed by an elaborated gene network. Considerable effort has been devoted to simplify its complexity by taking physics approaches to untangle the basic functional modules that are integrated to form the complete network: (1) A stochastic switch whose transition probability is controlled by two order parameters-population density and internal/external stress. (2) An adaptable timer whose clock rate is normalized by the same two previous order parameters. (3) Sensing units which measure population density and external stress. (4) A communication module that exchanges information about the cells' internal stress levels. (5) An oscillating gate of the stochastic switch which is regulated by the timer. The unique circuit architecture of the gate allows special dynamics and noise management features. The gate opens a window of opportunity in time for competence transitions, during which the circuit generates oscillations that are translated into a chain of short intervals with high transition probability. In addition, the unique architecture of the gate allows filtering of external noise and robustness against variations in circuit parameters and internal noise. We illustrate that a physics approach can be very valuable in investigating the decision process and in identifying its general principles. We also show that both cell-cell variability and noise have important functional roles in the collectively controlled individual decisions.


The Validity and Reliability of Borderline Personality Features Scale for Children-Short Form in Turkish Adolescents.
This study has aimed to investigate the validity and reliability of the Borderline Personality Features Scale for Children-Short Form (BPFSC-SF-TR) in Turkish adolescents. The study was carried out with adolescents between the ages of 12-18 from clinical (N=168) and community (N=181) backgrounds. All participants were asked to complete the BPFSC-SF-TR, the Personality Belief Questionaire - Short Form (PBQ-SF), the Brief Symptom Inventory (BSI) and the Personality Inventory for DSM-5- Short Form (PID-5-SF) scales. Also, the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version-Turkish Version (K-SADS-PL-TR) was administered to the participants in the clinical group and their parents were asked to complete the Pediatric Quality of Life Inventory (PEDsQL). Test-retest correlations and the Cronbach's α coefficients were calculated. BPFSC-SF-TR scores of both groups of participants positively correlated with the PBQ-BF borderline subscale, the PID-5-SF borderline related facets and the BSI scores, and negatively correlated with the PedsQL in the clinical group. Furthermore, the clinical group had higher total BPFSC-SF-TR scores than the community group, and their scores positively correlated with the number of diagnoses and psychiatric symptoms determined by using the KSADS-PL-TR. Exploratory and multi-group confirmatory factor analyses of the data of both groups supported a single factor structure. The Cronbach's α of the scale was 0.84 in the clinical group, and 0.79 in the community group. The test-retest reliability correlation coefficient of the scale was 0.71. The BPFSC-SF-TR is a valid and reliable tool for Turkish adolescents.


Total ankle arthroplasty.
Ankle arthritis has traditionally been treated surgically with arthrodesis (fusion) after conservative measures have been exhausted. The success of joint arthroplasty in the knee, hip, and shoulder inspired many attempts over the past 30 years to construct a workable ankle prosthesis. The failures of first generation prostheses caused skepticism regarding the feasibility of total ankle arthroplasty (TAR), but the mistakes of the past have been transformed into improvements and modifications. Today's second generation total ankle designs show promise, and outcomes are encouraging. The Agility Ankle (DePuy, Warsaw, IN) designed by Dr. Frank Alvine is featured in this article. The method of implant and postoperative management are reviewed.


Giant lipoma of the small bowel associated with perforated ileal diverticulum.
The authors present a rare case of the middle aged man who presented with a typical history and clinical findings suggestive of an acute appendicitis. After initial assessment, he required a surgical intervention. Operation findings revealed a perforated ileal diverticulum into a giant lipoma of the small bowel. The patient made a good postoperative recovery.


Impact of spot charge inaccuracies in IMPT treatments.
Spot charge is one parameter of pencil-beam scanning dose delivery system whose accuracy is typically high but whose required value has not been investigated. In this work we quantify the dose impact of spot charge inaccuracies on the dose distribution in patients. Knowing the effect of charge errors is relevant for conventional proton machines, as well as for new generation proton machines, where ensuring accurate charge may be challenging. Through perturbation of spot charge in treatment plans for seven patients and a phantom, we evaluated the dose impact of absolute (up to 5× 106 protons) and relative (up to 30%) charge errors. We investigated the dependence on beam width by studying scenarios with small, medium and large beam sizes. Treatment plan statistics included the Γ passing rate, dose-volume-histograms and dose differences. The allowable absolute charge error for small spot plans was about 2× 106 protons. Larger limits would be allowed if larger spots were used. For relative errors, the maximum allowable error size for small, medium and large spots was about 13%, 8% and 6% for small, medium and large spots, respectively. Dose distributions turned out to be surprisingly robust against random spot charge perturbation. Our study suggests that ensuring spot charge errors as small as 1-2% as is commonly aimed at in conventional proton therapy machines, is clinically not strictly needed.


Interferon regulatory factor 5 and autoimmune lupus.
Systemic lupus erythematosus (SLE) is a severe multi-system autoimmune disease, whereas interferon regulatory factor (IRF) 5 belongs to the family of transcription factors that modulate immune system activities. Recently, many lines of investigations suggested that IRF5 gene polymorphisms are closely associated with the disease onset of SLE. Indeed, expressed in B cells, dendritic cells (DCs), monocytes and macrophages, IRF5 could significantly affect these immune cells participating in the pathogenesis of SLE, and numerous studies implied that this transcription factor is mechanistically linked to the disease progression. Here, we comprehensively review the updated evidence indicating the roles of IRF5 in autoimmune lupus. Hopefully, the information obtained will lead to a better understanding of the pathogenesis and development of novel therapeutic strategies for the systemic autoimmune disease.


Vertical fracture and marginal bone loss of internal-connection implants: a finite element analysis.
Marginal bone loss around implants is of great concern, and its cause may be multifactorial. Recently, clinical cases presenting marginal bone loss, in most cases accompanied by vertical fracture of internal-connection implants in the buccolingual direction, have been reported, in which unfavorable stress distribution is one possible cause of marginal bone resorption. The purpose of the current study was to characterize this type of marginal bone loss and implant fracture by conducting a finite element analysis (FEA). Clinical and radiographic evaluations showed that the prostheses of all reported cases had implant-level setups and were directly screwed to the internal implants. Intriguingly, all vertical fractures reported were in the buccolingual direction. Therefore, to characterize the specific implant fractures, FEA was conducted with misfit models created for two different setups, abutment-level and implant-level, both with screw-retained prostheses. The models were subjected to initial misfits of 0 μm (representing perfect fit), 50 μm, 100 μm, 150 μm, or 200 μm, and vertical loading was then applied. FEA revealed that, for the implant-level setup, excessive stress at the neck of the implant gradually increased in the buccolingual direction as the misfit increased. This result was not seen for the abutment-level setup. A broad maximum stress distribution was evident for the implant-level setup but not for the abutment-level setup. Broad distribution of excessive stress in the FEA correlated to the clinical cases, and marginal bone loss in these cases may be associated with mechanical alterations. To avoid unnecessary complications, selection of an abutment-level setup is strongly suggested.


Production of insulin-like growth factor binding proteins (IGFBPs) by porcine granulosa cells: identification of IGFBP-2 and -3 and regulation by hormones and growth factors.
Using ligand blotting and immunoprecipitation we have characterized the insulin like growth factor binding proteins (IGFBPs) produced by cultured porcine granulosa cells. Ligand blot analysis of granulosa cell conditioned medium revealed 5 bands of IGF binding activity with apparent molecular sizes of 44, 40, 34, 29, and 22 kilodaltons (kDa). The 40-44 kDa bands of granulosa- conditioned medium were identified by immunoprecipitation with an antibody to porcine IGFBP-3, the acid-stable subunit of the 150 kDa GH-dependent serum IGFBP complex. The 34 kDa band was immunoprecipitated by an antibody to the rat IGFBP-2, the major IGFBP found in fetal rat serum and in BRL-3A cell cultures. To date we have been unable to immunoprecipitate the 29 and 22 kDa bands with any of the antibodies tested including a panel of monoclonal antibodies to human IGFBP-1, the amniotic fluid IGFBP. The pattern of secretion varied with size of the follicles from which granulosa cells were obtained and the culture conditions. With cells from small (2-4 mm) follicles, short term cultures secreted mainly IGFBP-3 and IGFBP-2, while IGFBP-2 and the 29 and 22 kDa bands were pronounced in longer term cultures. In short term culture, granulosa cells from medium sized (4-6 mm) porcine follicles produced IGFBPs in substantially greater amounts than did those from small (1-3 mm) follicles, but exhibited comparable band patterns. The production of IGFBPs was inhibited by cycloheximide. IGFBP production by granulosa cells in culture was regulated by hormones and growth factors. The most striking effects were the inhibition of IGFBP-3 secretion by transforming growth factor beta and FSH. In contrast, IGFBP-3 levels were enhanced by epidermal growth factor. The IGFBPs produced by cultured porcine granulosa cells are identical in size and immunoreactivity to those previously found in porcine follicular fluid. Thus, follicular cells may be the source of follicular fluid IGFBPs. The IGFBPs may be important modulators of the IGF autocrine/paracrine system in the ovary.


Loneliness and subjective physical health among war veterans: Long term reciprocal effects.
Poor subjective physical health and loneliness are among the most detrimental ramifications of trauma. Indeed, substantial research has examined the link between subjective physical health and loneliness, mainly focusing on how loneliness leads to poorer physical health. However, the effects of poor subjective physical health on loneliness, as well as the reciprocal effects of these two factors, have scarcely been examined. Even less is known regarding the course of these mutual effects among individuals who have been exposed to trauma. The current investigation examines the reciprocal effects of subjective physical health and loneliness among a group of war veterans over four decades. Two-hundred and seventy-four Israeli veterans from the 1973 Yom- Kippur War reported self-rated health (SRH), somatization and loneliness at 1991 (T1), 2003 (T2), 2008 (T3) and 2015 (T4). An autoregressive cross-lagged (ARCL) modeling strategy was employed to test the bidirectional relationship between subjective health and loneliness. The results showed that from T1 to T2, loneliness predicted subjective physical health. However, from T2 to T3, and from T3 to T4, subjective physical health predicted loneliness. PTSD moderated the association between loneliness and subjective physical health. The findings show a novel pattern of influences, demonstrating that the reciprocal effects of subjective physical health and loneliness change over time. The findings imply that subjective health and interpersonal experiences are inherently connected.


Abdominal drain amylase on the first day after pancreatectomy: a predictive factor for pancreatic fistula.
To analyze abdominal drain on the first postoperative day and evaluate its predictive nature for the diagnosis of Pancreatic Fistula exclusion, seeking to establish a cutoff point from which lower values demonstrate safety in excluding the possibility of this complication. From August 2017 to June 2020, data from 48 patients undergoing pancreatic resection were collected and analyzed from a prospective cohort. The patients were divided into two groups, one group consisting of patients who did not develop PF (Group A), and the other composed of patients who developed PF (Group B). The receiver operation characteristic curve was constructed, and cutoff points were evaluated by calculating sensitivity and specificity. Group A brought 30 patients together (62.5%) and Group B brought 18 patients together (37.5%). The 444 U/L value was the most satisfactory cutoff point for the receiver operation characteristic curve (CI 0.690-0.941), with a sensitivity of 94.4% and a specificity of 60%, thus being able to select 18 of 30 patients who did not succumb to PF. Abdominal drain on the first postoperative day can be used as a predictive factor in the diagnosis of PF exclusion (CI 0.690-0.941), with the value of 444 U/L being the best performance cutoff point.


In vivo ultrasonic debridement forces in bicuspids: a pilot study.
Hand instruments lead to application of excessive forces, resulting in extensive root substance removal. Ultrasonic debridement primarily removes accretions from root surfaces. However, there is a lack of information on procedural aspects of ultrasonic debridement. The purpose of the present study was to assess the forces applied by different therapists during ultrasonic root surface debridement of bicuspids in periodontal patients in vivo. Ten dentists and 10 dental hygienists each debrided 1 aspect of a bicuspid with moderate chronic periodontitis using an ultrasonic curet. The forces applied were recorded using a piezo-electric receiver built into the handle of the ultrasonic curet, an electronic transducer, and an analogous writer. The force recordings were converted from millivolts into Newtons (N). Mean positive and negative forces were calculated for each therapist, and t tests were used to assess differences in these forces between dentists and dental hygienists. The results showed that the mean positive force applied by dentists was 1.00 N (range 0.53 to 1.34 N). The corresponding mean value for dental hygienists was 0.77 N (range 0.20 to 1.22 N). The mean root debridement time was 110.2 seconds (range 38 to 165 seconds) for dentists and 90.8 seconds (range 38 to 244 seconds) for dental hygienists. The mean percentage of total debridement time used for positive force application by dentists was 76.1%, and for dental hygienists 63.9%. Negative forces impacting on the periodontal soft tissues were also recorded. These negative forces reached a mean of 0.16 N for dentists and 0.31 N for dental hygienists. From these observations, it may be concluded that application of ultrasonic debridement therapy is highly subjective, and that dentists and dental hygienists may not be adequately trained to use these instruments optimally.


Effects of acoustic heterogeneity in breast thermoacoustic tomography.
The effects of wavefront distortions induced by acoustic heterogeneities in breast thermoacoustic tomography (TAT) are studied. Amplitude distortions are shown to be insignificant for different scales of acoustic heterogeneities. For wavelength-scale, or smaller, heterogeneities, amplitude distortion of the wavefront is minor as a result of diffraction when the detectors are placed in the far field of the heterogeneities. For larger-scale heterogeneities at the parenchyma wall, by using a ray approach (geometric optics), we show that no refraction-induced multipath interference occurs and, consequently, that no severe amplitude distortion, such as is found in ultrasound tomography, exists. Next, we consider the effects of phase distortions (errors in time-of-flight) in our numerical studies. The numerical results on the spreads of point sources and boundaries caused by the phase distortions are in good agreement with the proposed formula. After that, we demonstrate that the blurring of images can be compensated for by using the distribution of acoustic velocity in the tissues in the reconstructions. The effects of the errors in the acoustical velocities on this compensation also are investigated. An approach to implement the compensation using only TAT data is proposed. Lastly, the differences in the effects of acoustic heterogeneity and the generation of speckles in breast TAT and breast ultrasound imaging are discussed.


Comparative evaluation of leukocyte- and platelet-rich plasma and pure platelet-rich plasma for cartilage regeneration.
Platelet-rich plasma (PRP) has gained growing popularity in the treatment of articular cartilage lesions in the last decade. However, the potential harmful effects of leukocytes in PRP on cartilage regeneration have seldom been studied in vitro, and not at all in vivo yet. The objective of the present study is to compare the effects of leukocyte- and platelet-rich plasma (L-PRP) and pure platelet-rich plasma (P-PRP) on cartilage repair and NF-κB pathway, in order to explore the mechanism underlying the function of leukocytes in PRP in cartilage regeneration. The constituent analysis showed that P-PRP had significantly lower concentrations of leukocytes and pro-inflammatory cytokines compared with L-PRP. In addition, cell proliferation and differentiation assays indicated P-PRP promoted growth and chondrogenesis of rabbit bone marrow mesenchymal stem cells (rBMSC) significantly compared with L-PRP. Despite similarity in macroscopic appearance, the implantation of P-PRP combining rBMSC in vivo yielded better cartilage repair results than the L-PRP group based on histological examination. Importantly, the therapeutic effects of PRP on cartilage regeneration could be enhanced by removing leukocytes to avoid the activation of the NF-κB pathway. Thus, PRP without concentrated leukocytes may be more suitable for the treatment of articular cartilage lesions.


Body composition and resting energy expenditure in clinically stable, non-weight-losing patients with severe emphysema.
To characterize the metabolic status of weight-stable and clinically stable individuals with advanced emphysema. Seventy-nine patients with severe emphysema (FEV(1), 29 +/- 13% of predicted [mean +/- SD]) evaluated for enrollment in the National Emphysema Treatment Trial and 20 age-matched healthy subjects were studied. Pulmonary function laboratory of university-affiliated teaching hospital. Data collection. We measured lung function, body composition, serum leptin levels, serum tumor necrosis factor receptors (sTNF-Rs), resting oxygen consumption (RVO(2)) normalized to weight in kilograms (RVO(2)/kg), and RVO(2) normalized to fat-free mass (FFM) [RVO(2)/FFM]. The patient group and healthy group had similar age, body mass index (BMI), and body composition. RVO(2)/kg, RVO(2)/FFM, and sTNF-R levels were higher in patients compared to healthy subjects. There were no differences in serum leptin levels between emphysematous and healthy subjects, and there was no correlation between leptin and sTNF-R and RVO(2)/kg. Furthermore, both groups had similar gender-related differences in FFM, percentage of body fat, and serum leptin levels. Patients with lower BMI showed the greatest differences from control subjects in RVO(2)/kg. In weight-stable subjects with advanced emphysema, RVO(2)/kg and RVO(2)/FFM were higher compared to healthy subjects, especially in those with BMI in the lower end of the normal range. RVO(2)/kg and RVO(2)/FFM did not correlate with leptin or sTNF-R levels. These data show that a higher metabolic rate is found in patients with emphysema who are clinically and weight stable. Thus, hypermetabolism is a feature of the disease and not sufficient to lead to weight loss.


Successful crizotinib rechallenge after crizotinib-induced organizing pneumonia in anaplastic lymphoma kinase-rearranged non-small cell lung cancer.
Crizotinib, a first-line anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor, has shown promising results for the treatment of locally advanced and metastatic lung cancer presenting the ALK rearrangement. On the other hand, secondary organizing pneumonia (OP) caused by anti-cancer drugs has been reported. While it is sometimes needed to rechallenge the suspected drug, the standard therapeutic strategy for secondary OP has not yet been established. We report a 60-year-old male with ALK-rearranged non-small cell lung cancer who developed crizotinib-induced OP and was successfully rechallenged with crizotinib. Six months after the rechallenge, the patient has achieved a partial response. To our knowledge, this is the first case in which crizotinib-induced OP has been successfully treated.


The English National Health Service: 1979--2005.
This article aims to assess the development of the English National Health Service (NHS) over the period 1979--2005, against the original, and often repeated, core objectives of the system: that it be universal in offering coverage to all members of the population in times of health care need; that it be comprehensive in its provision of health care services; and that it be (largely) free at the point of use. Comprehensiveness is open to interpretation, and may depend upon the wealth of the nation. Universality and (largely) free care at the point of use, which lend themselves to the principle of equal access for equal need, are more concrete, and it is not difficult to ascertain if they have been substantially and/or systematically violated. The article details briefly the developments in resource allocation, provider payment mechanisms, incentives and accountability, and notes that much of the emphasis on health sector change since the mid 1980s has been placed upon improving supply side efficiency and reducing waiting lists/times. Improving NHS efficiency, and indeed related aspirations associated with choice and health outcomes, can be perceived as 'secondary' objectives, in that they should not serve to undermine the core objectives of the system, assuming that the security offered by having an accessible, universal health care system is considered worthy of protection. The overall conclusion is that the NHS has performed quite well against its core objectives to date, although it is possible that the current preoccupation with choice and health outcomes will lead us down a different policy path in the future.


Development of pulmonary air leak in an extremely-low-birth-weight infant without mechanical ventilation: a case report.
A 34-year-old woman at 25 weeks 3 days was diagnosed with preterm labor and underwent an emergency cesarean section. The neonate did not cry or show any activity. The heart rate was 80 beats/min and the oxygen saturation on pulse oximetry (SpO2) was 77%. Immediately, positive pressure ventilation was delivered by T piece resuscitator, and then anesthesiologist performed endotracheal intubation. The neonate demonstrated severe cyanosis and the SpO2 dropped to 30%. Ventilation was not successful even after intubation, and we found neck crepitus, chest wall distension, and severe cyanosis on physical examination. We suspected tension pneumothorax and performed needle thoracentesis. The neonate was stabilized and transferred to the neonatal intensive care unit for further treatment, but expired on the 10th day of life. We report a case of pulmonary air leak developing tension pneumothorax, pneumomediastinum, subcutaneous emphysema in an extremely-low-birth-weight preterm infant immediately after birth.


Acupuncture in Osgood-Schlatter disease.
This article describes the use of acupuncture in the management of knee pain in Osgood-Schlatter disease. Manual and electroacupuncture were used. The patient responded well to acupuncture and found it effective in relieving his knee pain. Acupuncture should be considered in Osgood-Schlatter disease, both to manage the pain and to limit the need to take oral analgaesics for a prolonged period.


Augmin deficiency in neural stem cells causes p53-dependent apoptosis and aborts brain development.
Microtubules that assemble the mitotic spindle are generated by centrosomal nucleation, chromatin-mediated nucleation, and nucleation from the surface of other microtubules mediated by the augmin complex. Impairment of centrosomal nucleation in apical progenitors of the developing mouse brain induces p53-dependent apoptosis and causes non-lethal microcephaly. Whether disruption of non-centrosomal nucleation has similar effects is unclear. Here, we show, using mouse embryos, that conditional knockout of the augmin subunit Haus6 in apical progenitors led to spindle defects and mitotic delay. This triggered massive apoptosis and abortion of brain development. Co-deletion of Trp53 rescued cell death, but surviving progenitors failed to organize a pseudostratified epithelium, and brain development still failed. This could be explained by exacerbated mitotic errors and resulting chromosomal defects including increased DNA damage. Thus, in contrast to centrosomes, augmin is crucial for apical progenitor mitosis, and, even in the absence of p53, for progression of brain development.


The spectrum of monogenic autoinflammatory syndromes: understanding disease mechanisms and use of targeted therapies.
Monogenic autoinflammatory diseases encompass a distinct and growing clinical entity of multisystem inflammatory diseases with known genetic defects in the innate immune system. The diseases present clinically with episodes of seemingly unprovoked inflammation (fever, rashes, and elevation of acute phase reactants). Understanding the genetics has led to discovery of new molecules involved in recognizing exogenous and endogenous danger signals, and the inflammatory response to these stimuli. These advances have furthered understanding of innate inflammatory pathways and spurred collaborative research in rheumatology and infectious diseases. The pivotal roles of interleukin (IL)-1beta in cryopyrin-associated periodic syndromes, tumor necrosis factor (TNF) in TNF receptor-associated periodic syndrome, and links to inflammatory cytokine dysregulation in other monogenic autoinflammatory diseases have resulted in effective therapies targeting proinflammatory cytokines IL-1beta and TNF and uncovered other new potential targets for anti-inflammatory therapies.


OIP5-AS1 contributes to the development in endometrial carcinoma cells by targeting miR-152-3p to up-regulate SLC7A5.
Endometrial carcinoma (EC) is one common gynecological tumor, threatening physical and psychological health of females. Huge amount of essays indicated that long non-coding RNAs (lncRNAs) were widely reported to serve as a crucial regulator in the biological movements among multiple carcinomas, including EC. RT-qPCR was implemented to detect the expression of target genes. Loss/gain-of-function experiments certified the impacts of OIP5-AS1 and miR-152-3p on EC cell progression. Data of this research suggested that powerful expression of OIP5-AS1 was discovered in EC cell lines. Loss/gain-of-function assays inferred that OIP5-AS1 promoted proliferative, migratory and invasive abilities, and Epithelial-Mesenchymal Transition (EMT). In addition, we identified miR-152-3p expression was negatively modulated by OIP5-AS1. OIP5-AS1 accelerated the development of EC cells via downregulating miR-152-3p expression. SLC7A5 was selected out as a downstream target of miR-152-3p. The competing relationship between OIP5-AS1 and SLC7A5 was corroborated by luciferase reporter assay. Eventually, the results of rescue assays indicated that SLC7A5 overexpression could restore the impacts of OIP5-AS1 ablation on the progression of EC cells. Our research confirmed that OIP5-AS1 propeled the development of EC cells through targeting miR-152-3p/SLC7A5. OIP5-AS1 could be utilized as a target for EC treatment.


Malting-A method for modifying volatile composition of black, brown and green lentil seeds.
Technique of malting legume seeds is not currently widespread among scientists as well as industrial maltsters. However, this method of seed modification is successfully used by humankind for millennia to improve technological parameters, as well as change taste and aroma of various food products. Three lentil cultivars (black, brown and green) were malted (steeped, germinated for three various time periods and then kilned) to produce nine lentil malts. Malting had significant influence on the volatile composition of lentil seeds. Total concentration of volatiles in the green lentils increased and decreased in the case of black and brown lentils after malting procedure. However, most importantly, in every lentil cultivar the contribution of various groups of compounds (such as aldehydes, alcohols, terpenes or ketones) to the overall volatilome was changed due to the malting procedure.


[The significance and place of HBsAg neutralization test in the diagnosis and algorithm of hepatitis B infection].
The diagnosis of hepatitis B virus infection is evaluated serologically, virologically, biochemically, and with histologic liver indicators. The aim of this study was to investigate the place and significance of the HBsAg neutralization test in the diagnostic algorithm for hepatitis Binfection. From the venous blood samples sent to Ankara Numune Education and Research Hospital Medical Microbiology Laboratory between September 2014 and May 2016 for HBsAg test, serum samples regarded each patient as reactive (≥ 0.9 S\CO) , 9 ≤ S ≤ CO ≤ 30) were studied twice. A total of 105 samples which were reactive in both analyses were included in the study. After the evaluation of these samples by neutralization confirmation test, which is routinely performed in our laboratory, the samples were stored under optimal conditions and studied for HBV DNA with the real-time PCR and for HBeAg, anti-HBeAg, anti-HBc IgM, and anti-HBc total antibody assays by ELISA. The 105 samples, in which HBsAg was detected, were analyzed with the neutralization test. The presence of HBsAg was confirmed by neutralization test in 67 of 105 samples (63.8%), and of these patients, two patients (2.3%) had negative HBV DNA and anti-HBc total antibody test (false positive neutralization test). Of the 105 samples included in the study, the anti-HBc total antibody test was positive in 78 patients (74.3%). However, out of these 78 patients who were positive for the anti-HBc total antibody test, there were 13 patients (16.7%) with negative neutralization and HBV DNA test results (false positive anti-HBc total antibody test). The HBV DNA positivity was detected significantly lower in samples with HBsAg level ≤ 5 S/CO compared to the samples with HBsAg level > 5 S/CO (p= 0.020). Also, if the unit price of the neutralization test used in our study was considered, the cost was 17,00 TL while the unit price of HBV DNA test was 55,00 TL. Utilization of the neutralization test instead of HBV DNA test provides a saving of 38,00 TL per patient. The use of the neutralization test as a validation test when the HBsAg titre was less than or equal to 5S/CO will significantly reduce the cost of the test without the need for HBV DNA test. We suggest that if both the neutralization test and the anti-HBc total antibody test is negative in a sample with an HBsAg titration higher than 5 S/CO, the decision can be made without the need for HBV DNA test. However; if the neutralization test is negative, but the anti-HBc total antibody test is positive, then HBV DNA needs to be determined to eliminate the inconsistency between neutralization and anti-HBc total antibody assays. At the same time, we found that the use of anti-HBc total antibody test along with HBsAg as a screening test did not provide any advantage since the anti-HBc total antibody test was detected to have a high false positivity (16.7%) rate.


Protein Localization and Interaction Studies in Plants: Toward Defining Complete Proteomes by Visualization.
Protein interaction and localization studies in plants are a fundamental component of achieving mechanistic understanding of virus:plant interactions at the systems level. Many such studies are conducted using transient expression assays in leaves of Nicotiana benthamiana, the most widely used experimental plant host in virology, examined by laser-scanning confocal microscopy. This chapter provides a workflow for protein interaction and localization experiments, with particular attention to the many control and supporting assays that may also need to be performed. Basic principles of microscopy are introduced to aid researchers in the early stages of adding imaging techniques to their experimental repertoire. Three major types of imaging-based experiments are discussed in detail: (i) protein localization using autofluorescent proteins, (ii) colocalization studies, and (iii) bimolecular fluorescence complementation, with emphasis on judicious interpretation of the data obtained from these approaches. In addition to establishing a general framework for protein localization experiments in plants, the need for proteome-scale localization projects is discussed, with emphasis on nuclear-localized proteins.


Insulin antagonism: a novel role for human serum transferrin.
We have purified alpha2-glycoprotein (alpha2-GP), an insulin antagonist from human plasma which is induced by growth hormone (GH), and shown that pure alpha2-GP is a potent antagonist of severe insulin-induced hypoglycemia, producing acute hyperglycemia in intact rats and ketonuria in diabetic rats. The N-terminal amino acid sequence of alpha2-GP and the reactivity of alpha2-GP with an antitransferrin monoclonal antibody show that alpha2-GP is identical to human serum transferrin. Furthermore, pure human serum transferrin and non-glycosylated recombinant human transferrin reproduce the insulin antagonist effects of alpha2-GP in rats, whereas ovotransferrin shows no such effect. The neutralization of the insulin antagonism of human serum transferrin by an anti-transferrin monoclonal antibody shows that transferrin has a new function as a potent insulin antagonist. This novel role for human serum transferrin in the regulation of glucose metabolism provides a reasonable mechanism for the diabetogenic effect of GH, and has important implications for the etiology and progression of diabetes.


Cultural safety: a new concept in nursing people of different ethnicities.
Cultural safety is a concept which has been developed by Maori nurses in New Zealand in order to reflect on nursing practice from their point of view as the indigenous minority in our country. The paper contrasts this new concept critically with Leininger's well-known model of transcultural nursing in order to suggest its potential significance. To date work on cultural safety in New Zealand has focused on the attitudes which individual nurses bring to their practice, attempting to change the effects of their social conditioning on their approach to nursing. The paper supports the view that all nursing care is provided in a social context which influences its efficacy, and specifies that the structural elements, such as the institutional context within which nursing care is provided and policies which influence how care is the provided, need to be explicitly recognized. The paper concludes that until the effects on the health care system of inequalities in power between groups in society are addressed we cannot ensure that the needs of persons from minority cultures will be met. Because it illuminates this dimension of nursing care, cultural safety is a concept of general significance for all nurses.


miR-34b-3p May Promote Antiplatelet Efficiency of Aspirin by Inhibiting Thromboxane Synthase Expression.
Aspirin has been widely used for the prevention of cardiovascular diseases, but its antiplatelet efficiency varies between individuals. The present study aimed to evaluate response to aspirin based on gene profiles as well as potential regulating pathways using human blood samples and cell lines. Platelet function in patients 50 years or older with coronary artery disease on 100 mg/day aspirin was measured by light transmission aggregometry (LTA) of arachidonic acid (AA)-induced platelet aggregation. The expression of eight candidate genes-PTGS1/COX1, PLA2G4A, PLA2G6, PLA2G7, TBXAS1, TBXA2R, PTGIR, and ITGA2B-and the ingredients involved in AA metabolism were analyzed. Our data showed that the expressions of thromboxane A synthase 1 (TBXAS1), thromboxane synthase (TXS), and thromboxane B2 (TXB2) were increased in the upper quartile of platelet aggregation (LTA-AA_Q4) group compared with the lower quartile of platelet aggregation (LTA-AA_Q1) group. Our bioinformatics analysis suggested that TBXAS1 was targeted by miR-34b-3p via binding to its 3'-UTR, which was subsequently verified experimentally. Although overexpression of miR-34b-3p exhibited no apparent effect on cell proliferation, inhibition of miR-34b-3p promoted megakaryocyte viability. Our data demonstrated that the expression of TBXAS1 was higher in the aspirin hyporesponsiveness group than that in the hyperresponsiveness group, suggesting that high expression of TBXAS1 may be associated with aspirin hyporesponsiveness. miR-34b-3p may regulate the platelet and aspirin response by suppressing TBXAS1 expression and megakaryocyte proliferation.


Acute management of nutritional demands after spinal cord injury.
A systematic review of the literature was performed to address pertinent clinical questions regarding nutritional management in the setting of acute spinal cord injury (SCI). Specific metabolic challenges are present following spinal cord injury. The acute stage is characterized by a reduction in metabolic activity, as well as a negative nitrogen balance that cannot be corrected, even with aggressive nutritional support. Metabolic demands need to be accurately monitored to avoid overfeeding. Enteral feeding is the optimal route following SCI. When oral feeding is not possible, nasogastric, followed by nasojejunal, then by percutaneous endoscopic gastrostomy, if necessary, is suggested.


Differential activation of stress-responsive signalling proteins associated with altered loading in a rat skeletal muscle.
Skeletal muscle undergoes a significant reduction in tension upon unloading. To explore intracellular signalling mechanisms underlying this phenomenon, we investigated twitch tension, the ratio of actin/myosin filaments, and activities of key signalling molecules in rat soleus muscle during a 3-week hindlimb suspension and 2-week reloading. Twitch tension and myofilament ratio (actin/myosin) gradually decreased during unloading but progressively recovered to initial levels during reloading. To study the involvement of stress-responsive signalling proteins during these changes, the activities of protein kinase C alpha (PKCalpha) and three mitogen-activated protein kinases (MAPKs)--c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), and p38 MAPK--were examined using immunoblotting and immune complex kinase assays. PKCalpha phosphorylation correlated positively with the tension (Pearson's r = 0.97, P < 0.001) and the myofilament ratio (r = 0.83, P < 0.01) over the entire unloading and reloading period. Treatment of the soleus muscle with a PKC activator resulted in a similar paralleled increment in both PKCalpha phosphorylation and the alpha-sarcomeric actin expression. The three MAPKs differed in the pattern of activation in that JNK activity peaked only for the first hours of reloading, whereas ERK and p38 MAPK activities remained elevated during reloading. These results suggest that PKCalpha may play a pivotal role in converting loading stress to intracellular changes in contractile proteins that determine muscle tension. Differential activation of MAPKs may also help alleviate muscle damage, modulate energy transport and/or regulate the expression of contractile proteins upon altered loading.


Entrapment of a tined pacemaker electrode in the tricuspid valve. A case report.
A tined pacemaker electrode was entrapped in the tricuspid valve apparatus. Nonresponding, sustained ventricular tachycardia, and cardiac arrest necessitated forcible removal of the electrode causing partial avulsion of the tricuspid valve. Hemodynamically insignificant tricuspid regurgitation developed subsequently.


Antigen-induced neutrophil chemotactic factor from cloned human T lymphocytes.
Here we report the presence of a low molecular weight (10,000 neutrophil chemotactic factor (NCF) in the supernatants of activated human T lymphocytes. Appreciable amounts of the 10,000 MW NCF were generated by peripheral blood mononuclear cells (PBMC) stimulated with anti-CD3 antibody, and comparable NCF was secreted by both long-term human T-helper (CD4+) cell lines reactive with house dust mite (Dermatophagoides farinae) and influenza A virus-immune T-cell clones. When the cloned T cells were stimulated with specific antigen in the presence of irradiated accessory cells (AC) or insolubilized anti-CD3 antibody the 10,000 MW NCF was readily identifiable in 24-hr culture supernatants. Cultures of AC and antigen alone produced negligible neutrophil chemotactic activity, as did control cultures using an irrelevant allergen (mixed grass pollen). These findings indicate that the 10,000 MW NCF may be T-lymphocyte derived and that formation and release are dependent upon stimulation via the antigen receptor.


Curcumin Inhibits HGF-Induced EMT by Regulating c-MET-Dependent PI3K/Akt/mTOR Signaling Pathways in Meningioma.
Meningiomas, which are the most common primary intracranial tumors, have highly aggressive cells in malignant cases. Due to its extensive antitumor effects, curcumin is widely used in experimental and clinical studies. However, the role of curcumin during the epithelial-mesenchymal transition (EMT) in meningioma has not been established. We found that curcumin blocks hepatocyte growth factor- (HGF-) induced proliferation, migration, invasion, and EMT of human malignant meningioma cells by regulating the PI3K/Akt/mTOR signaling pathway. In addition, treatment of human malignant meningioma cells with the tyrosine protein kinase (c-MET) inhibitor (SU11274) or the phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) suppressed HGF-induced migration and EMT. Furthermore, we found that curcumin inhibited tumor growth and HGF-induced EMT in mice subjected to subcutaneous xenotransplantation. These findings indicate that HGF regulates EMT in human malignant meningioma cells through c-MET/PI3K/Akt/mTOR modulation. In conclusion, curcumin inhibits HGF-induced EMT by targeting c-MET and subsequently blocking the PI3K/Akt/mTOR pathway.


During stress, heart rate variability moderates the impact of childhood adversity in women with breast cancer.
Childhood adversity has long-lasting neuro-biological effects that can manifest as exaggerated stress responsivity to environmental challenge. These manifestations include a dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis as well as increased levels of inflammatory mediators in response to stress. In this investigation, vagal parasympathetic activity was assessed for its capacity to moderate the relationship between childhood adversity and stress responsivity (cortisol and inflammation) during an acute laboratory challenge (Trier Social Stress Test-TSST). Thirty women recently diagnosed with breast cancer underwent the TSST during which their heart rate was recorded and saliva samples collected for measurement of cortisol and the proinflammatory cytokine, IL-6. Vagal activity during the TSST was calculated as the high-frequency (HF) component of heart rate variability (HRV). Vagal activity during the TSST moderated the effect of childhood adversity on both the cortisol and the IL-6 response. Women who had lower vagal stress-reactivity during the TSST and reported greater childhood adversity showed a larger rise in cortisol and IL-6 when compared to women with lower childhood adversity. The findings demonstrate that women with exposure to childhood adversity and low vagal stress-reactivity (reduced parasympathetic activity) exhibit an elevated stress response characterized by greater cortisol and proinflammatory cytokine release. Inflammatory burden and HPA dysregulation subsequent to stress may impair cancer control.


Haemoglobin E in pregnancy. A case report. Diagnosis, familiar study and counselling, follow up until delivery and new-born observation.
Haemoglobin E is a beta chain variant quite common in Southeastern Asia. The case of a gravid Thai woman with a microcytic anaemia is reported. The diagnosis of homozygous haemoglobin E was suspected on the basis of ethnic considerations when analysis of her haemoglobin showed the absence of normal HbA1 and about 100% of a variant Hb with electrophoretic mobility with HbC and HbA2. Identification of the haemoglobin variant was performed by using an association of alkaline electrophoresis on agarose gel, acid electrophoresis on agarose gel, haemoglobin isoelectrofocusing, high performance liquid chromatography. A study of haemoglobin pattern in the partner, parents and siblings was also performed. Pregnancy continued without any problems until the 40th week when a caesarean section was performed due to a difficult labour with foetal distress. The haemoglobin pattern of the new-born was studied at birth and after 1 year; as expected, it was quite normal at birth and a heterozygous condition for HbE was observed after 1 year. HbE, in even heterozygous and homozygous states, gives a mild clinical picture but its association with other haemoglobinopathies, such as a double heterozygous state (i.e. HbE/beta Thalassaemia) gives rise to a severe transfusion dependent thalassaemia syndrome. It is the authors' opinion that only a strict interaction between obstetricians and pathologists is the possible correct answer to the new diagnostic question proposed by a rapidly evolving inter-ethnic society.


Domain-Dependent Evolution Explains Functional Homology of Protostome and Deuterostome Complement C3-Like Proteins.
Complement proteins emerged early in evolution but outside the vertebrate clade they are poorly characterized. An evolutionary model of C3 family members revealed that in contrast to vertebrates the evolutionary trajectory of C3-like genes in cnidarian, protostomes and invertebrate deuterostomes was highly divergent due to independent lineage and species-specific duplications. The deduced C3-like and vertebrate C3, C4 and C5 proteins had low sequence conservation, but extraordinarily high structural conservation and 2-chain and 3-chain protein isoforms repeatedly emerged. Functional characterization of three C3-like isoforms in a bivalve representative revealed that in common with vertebrates complement proteins they were cleaved into two subunits, b and a, and the latter regulated inflammation-related genes, chemotaxis and phagocytosis. Changes within the thioester bond cleavage sites and the a-subunit protein (ANATO domain) explained the functional differentiation of bivalve C3-like. The emergence of domain-related functions early during evolution explains the overlapping functions of bivalve C3-like and vertebrate C3, C4 and C5, despite low sequence conservation and indicates that evolutionary pressure acted to conserve protein domain organization rather than the primary sequence.


Synthesis and electrochemical properties of LiMPO4 (M = Fe, Mn, Co) nanocrystals in polyol medium.
Olivine structured LiMPO4 (M = Fe, Mn, Co) was synthesized by the solvothermal process using a polyol medium of diethylene glycol (DEG) without any further heating as a post procedure. The synthesized LiMPO4 nanoparticles exhibited an average length of 200 approximately 400 nm, width of 200 approximately 300 nm, and thickness of 20 approximately 50 nm, and with well dispersed plate and rod morphologies. The Rietveld-refined X-ray diffraction (XRD) pattern of LiFePO4 exhibited a good fit with an olivine structure (space group: Pnma) and no undesirable impurity phases. The LiFePO4 nanocrystals showed a reversible capacity of 167 mAh/g, equating to a utilization efficiency of 98% of its theoretical capacity, with a good cyclability over an extended range up to 40 cycles.


A fast stabliization technique for oxygen sensors with low cathode current densities.
After application of the polarization voltage to a newly prepared oxygen sensor, an initial stabilization of several minutes to a few hours is required. The electrochemical phenomena accounting for this stabilization process are discussed. By far the slowest reaction is the change of the oxidation state of the noble metal cathode after application of the polarization voltage. During this process, reduction of surface oxides at the cathode causes a transient current. The contribution of this reaction to the total current is proportionately higher in the case of oxygen sensors with low cathode current densities (large cathode, membrane of low oxygen permeability) than in the case of sensors with microcathodes. For the first type of sensor, a technique has been developed which allows acceleration of this surface reaction by passing a high constant current across the cathode. With this technique, the stabilization time can be considerably shortened in a reproducible manner, and the sensor is ready to be used within 15 to 30 min of its preparation. This time is comparable to the stabilization time needed for sensors with microcathodes.


Haemorheological profile in patients with systemic sclerosis.
The relationship between rheological alterations and systemic sclerosis (SSc) is not well established. We have determined in 27 patients with SSc (4 male, 21 female ) aged 59 +/- 14 years and in a well matched control group the whole rheological profile, i.e. blood viscosity (BV), plasma viscosity (PV), erythrocyte aggregation (EA), erythrocyte deformability (ED) along with fibrinogen (Fbg), C-reactive protein (CRP), lipids, and erythrocyte indices. Patients show higher Fbg, PV and EA (P<0.01) and lower ED (P<0.01). A negative significant correlation was found between ED and inflammation markers, both CRP (P<0.05) and Fbg (P<0.01), indicating that decreased ED seems to be related to inflammatory changes at microcirculatory levels. In addition, patients with anticentromere antibodies show significantly lower ED than those without (P<0.05). The clinical significance of this observation needs to be clarified, deserving further research.


The activity of Sac1 across ER-TGN contact sites requires the four-phosphate-adaptor-protein-1.
Phosphatidylinositol-4-phosphate (PI4P), a phosphoinositide with key roles in the Golgi complex, is made by Golgi-associated phosphatidylinositol-4 kinases and consumed by the 4-phosphatase Sac1 that, instead, is an ER membrane protein. Here, we show that the contact sites between the ER and the TGN (ERTGoCS) provide a spatial setting suitable for Sac1 to dephosphorylate PI4P at the TGN. The ERTGoCS, though necessary, are not sufficient for the phosphatase activity of Sac1 on TGN PI4P, since this needs the phosphatidyl-four-phosphate-adaptor-protein-1 (FAPP1). FAPP1 localizes at ERTGoCS, interacts with Sac1, and promotes its in-trans phosphatase activity in vitro. We envision that FAPP1, acting as a PI4P detector and adaptor, positions Sac1 close to TGN domains with elevated PI4P concentrations allowing PI4P consumption. Indeed, FAPP1 depletion induces an increase in TGN PI4P that leads to increased secretion of selected cargoes (e.g., ApoB100), indicating that FAPP1, by controlling PI4P levels, acts as a gatekeeper of Golgi exit.


NAD(+)-dependent D-2-hydroxyisocaproate dehydrogenase of Lactobacillus delbrueckii subsp. bulgaricus. Gene cloning and enzyme characterization.
A genomic library from Lactobacillus delbrueckii subsp. bulgaricus was used to complement an Escherichia coli mutant strain deficient for both lactate dehydrogenase and pyruvate formate lyase, and thus unable to grow anaerobically. One recombinant clone was found to display a broad specificity NAD(+)-dependent D-2-hydroxyacid dehydrogenase activity. The corresponding gene (named hdhD) was subcloned and sequenced. The deduced amino acid sequence of the encoded enzyme indicates a 333-residue protein closely related to D-2-hydroxyisocaproate (i.e. 2-hydroxy-4-methyl-pentanoate) dehydrogenase (D-HO-HxoDH) of Lactobacillus casei and other NAD(+)-dependent D-lactate dehydrogenases (D-LDH) from several other bacterial species. The hdhD gene was overexpressed under the control of the lambda phage PL promoter and the enzyme was purified with a two-step method. The L. delbrueckii subsp. bulgaricus enzyme, like that of L. casei, was shown to be active on a wide variety of 2-oxoacid substrates except those having a branched beta-carbon.


Effective gene prediction by high resolution frequency estimator based on least-norm solution technique.
Linear algebraic concept of subspace plays a significant role in the recent techniques of spectrum estimation. In this article, the authors have utilized the noise subspace concept for finding hidden periodicities in DNA sequence. With the vast growth of genomic sequences, the demand to identify accurately the protein-coding regions in DNA is increasingly rising. Several techniques of DNA feature extraction which involves various cross fields have come up in the recent past, among which application of digital signal processing tools is of prime importance. It is known that coding segments have a 3-base periodicity, while non-coding regions do not have this unique feature. One of the most important spectrum analysis techniques based on the concept of subspace is the least-norm method. The least-norm estimator developed in this paper shows sharp period-3 peaks in coding regions completely eliminating background noise. Comparison of proposed method with existing sliding discrete Fourier transform (SDFT) method popularly known as modified periodogram method has been drawn on several genes from various organisms and the results show that the proposed method has better as well as an effective approach towards gene prediction. Resolution, quality factor, sensitivity, specificity, miss rate, and wrong rate are used to establish superiority of least-norm gene prediction method over existing method.


The place of inpatient care in the treatment of anorexia nervosa: questions to be answered.
The chance that an anorexia nervosa patient will be hospitalized depends more on circumstantial rather than on scientifically based factors. Although there is a lot of information on the treatment of anorexia nervosa patients in a residential setting, answers to questions relating to the "when," "where," and "how" of treatment are subjective. There is no clinical consensus and the paucity of controlled research is hampering the development of an evidence-based practice. Increasing economic restraints through managed care policies limit the length of inpatient treatment, which leads to early discharge at a lower body weight, which leads to a higher likelihood of readmissions, which leads to increasing costs. We will highlight important issues in the ongoing debate between economic demands and clinical challenges. Our goal is to stimulate critical reflections and systematic research.


Effect of mabuterol on tracheal mucociliary clearance of magnetized iron particles in anesthetized dogs.
We studied the effect of mabuterol on the tracheal mucociliary clearance of magnetized iron particles in anesthetized dogs. A catheter was inserted directly into the trachea through the mouth and 0.05 ml of saline solution with 30 mg of Fe3O4 was instilled into the trachea. After magnetization from outside the chest wall, the remanent magnetic field (RMF) strength generated in the trachea was sequentially measured with a flux-gate magnetometer. The decay of RMF immediately after sequential magnetization showed a clearance of Fe3O4 particles. Mabuterol (10 micrograms/kg) increased clearance as much as isoproterenol (10 micrograms/kg) 30 min after intravenous injection relative to control measurement (p less than 0.01). These results suggest that mabuterol is useful to promote clearance.


A comparison of diode laser and Er:YAG lasers in the treatment of gingival melanin pigmentation.
This study compared the use of diode and Er:YAG lasers in treating gingival melanin pigmentation (GMP) in terms of gingival depigmentation, local anesthesia requirements, postoperative pain/discomfort, depigmentation effectiveness, and total treatment duration. Twenty patients (13 female, 7 male) referred with GMP were enrolled in the study. Patients were randomly divided into 2 groups. Group 1 was treated with a gallium aluminum arsenide diode laser with a continuous wavelength of 808 nm, and group 2 was treated with an Er:YAG laser with a continuous wavelength of 2,940 nm. Gingival depigmentation was performed by applying the laser at 1 W. Treatment was administered on a weekly basis until a normal pink gingival color was observable in clinical examination and photographs. In addition, patients were asked to evaluate the procedure by using a self-administered questionnaire. Procedures were carried out without the need for any topical or local anesthetic, and no unpleasant events occurred during the actual procedure or the healing period. The total length of treatment was significantly shorter with the diode laser (group 1) than with the Er:YAG laser (group 2; P < .05). No melanin recurrence was detected during any follow-up session. Diode and Er:YAG lasers administered at 1 W both result in satisfactory depigmentation of GMP.


Rickettsial Cerebellitis: A Rare Neurological Manifestation.
Scrub typhus is a vector-borne disease caused by gram-negative bacilli, Orientia tsutsugamushi. The vector of scrub typhus is the mite. The clinical manifestations often present with either a simple fever or life-threatening multi-organ dysfunction. Neurological manifestations also vary, and the incidence of neurological manifestations is unknown. Cerebellitis is one of the rare neurological manifestations associated with scrub typhus. In this case report, we present the case of a 35-year-old man who tested positive for scrub typhus (IgM enzyme-linked immunosorbent assay (ELISA) blood test) with a history of fever and cerebellar signs and symptoms. He was managed with antibacterial agents and made a good recovery.


Undergraduate Confidence When Undertaking Root Canal Treatment and Their Perception of the Quality of Their Endodontic Education.
The General Dental Council expects graduating dentists to be competent at treating pulpal disease. Previous studies have found dental undergraduates to have low levels of confidence with respect to endodontic treatments. The aim of this study was to investigate the confidence of undergraduate dental students at the University of Bristol when performing root canal treatment, and to investigate their perception of the quality of their endodontic education. An anonymous questionnaire, based upon one used in a 2015 study at Cardiff University, was distributed to all (n = 204) undergraduate students in Years 3-5 at the University of Bristol. The results were analysed using the Statistical Package for the Social Sciences software (SPSS). There was a 59% (n = 120) response rate and a significant (p < 0.01) difference in confidence levels for root canal treatments (RCTs) completed between these students. All (100%) Year-5 students felt confident in completing anterior RCTs, and 91% felt confident in completing posterior RCTs. The majority (93%) of Year-4 students felt confident in completing anterior RCTs, and 77% felt confident in completing posterior RCTs. Over one-half (56%) of Year-3 students felt confident in anterior RCTs and 17% in posterior RCTs. With respect to the individual stages of RCT (access cavity, cleaning and shaping of root canal system, and obturation/filling), results showed that there was a significant difference (p < 0.01) in confidence levels between year groups. Many students thought the amount of time spent on endodontic teaching and the quality of teaching to be satisfactory. Improvements suggested for future endodontic teaching included higher numbers of staff supervision and additional endodontic practice on extracted teeth before seeing patients. There was a strong association between students' clinical experience and their levels of confidence when completing RCT. Increasing the amount of clinical experience of RCTs could enhance students' confidence further.


Drug-photosensitized protein modification: identification of the reactive sites and elucidation of the reaction mechanisms with tiaprofenic acid/albumin as model system.
Certain drugs can photosensitive the formation of protein modifications, which are thought to be responsible for the occurrence of photoallergy. In the present work, the UV irradiation of serum albumin in the presence of tiaprofenic acid has been studied as a model system for drug-photosensitized protein modifications. The photolysates evidenced that His, Tyr, and Trp are the reactive sites of the protein. The experimental results strongly suggest that formal hydrogen abstraction from the OH or NH groups of Tyr or Trp by the excited drug is the key photochemical process. Competition between cage escape and in cage recombination of the resulting radical pairs governs the final outcome: protein photo-cross-linking versus drug-protein adduct formation. These findings are highly relevant to understand the process of photohapten formation, the first event in the onset of photoallergy.


A Multifaceted Approach to Treatment of Recalcitrant Cutaneous Periorbital Juvenile Xanthogranuloma.
To demonstrate novel treatments for patients with high juvenile xanthogranuloma (JXG) eyelid lesion burden. A 14-year-old girl was referred to the oculoplastic surgery service for management of worsening extensive bilateral eyelid and adnexal lesions in the setting of JXG. The patient underwent intra-lesional steroid injections, serial excisions, and reconstruction with skin grafts. She was subsequently treated with CO 2 laser-assisted topical steroid application, which resulted in lesion regression. A novel multimodal approach to treatment of severe periocular JXG, incorporating surgical debulking, skin autograft, CO2 laser, and intra-lesional steroids, can be effective for lesion control.


Toxicity of a cadmium-contaminated diet to Hyalella azteca.
Four- and 10-week chronic toxicity tests were conducted using the freshwater amphipod Hyalella azteca and Cd-contaminated Chlorella sp. as a food source. Chlorella sp. was cultured in various Cd concentrations, filtered from solution, rinsed, dried, and ground into food flakes for the H. azteca. Unlike Cd toxicity from water sources, growth was found to be a more sensitive toxicological endpoint than survival, with calculated 50 and 25% effect concentrations (EC50s and EC25s, respectively) of 5.43 and 2.82 nmol/g, respectively, for Cd measured in food. Based on the regression of Cd in Chlorella sp. against Cd in filtered culture medium, the EC50 and EC25 corresponded to dissolved Cd concentrations of 11.30 and 5.09 nmol/L, respectively. Little or no bioaccumulation of Cd was found in the tissues of H. azteca that were fed contaminated food. These results demonstrate an apparent toxicological effect (either direct or indirect) of Cd-contaminated Chlorella sp. to H. azteca that is not associated with Cd accumulation. Toxicity of Cd-contaminated Chlorella sp. differs from waterborne Cd toxicity both in terms of the most sensitive endpoint (growth vs survival) and the relationship between toxicity and bioaccumulation. Unlike Cd toxicity through water exposure, Cd bioaccumulation by H. azteca cannot, therefore, be used to infer toxicity of Cd in a diet of Chlorella sp. Although the concentration of Cd in the algal culture medium that ultimately reduced growth of H. azteca in the present study was higher than Cd in water, which caused mortality to H. azteca in water-only tests during previous studies, further research regarding the contribution of dietary Cd to overall Cd toxicity is needed to verify that water-quality guidelines and risk assessments based on water-only exposures are fully protective.


Association between Three Low-Carbohydrate Diet Scores and Lipid Metabolism among Chinese Adults.
This study investigated the blood lipid levels of 5921 Chinese adults aged >18 years using data from the China Health and Nutrition Survey 2009. Diet information was collected through 3 day, 24 h recalls by trained professionals. The low-carbohydrate diet (LCD) score was determined according to the percentage of energy obtained from carbohydrate, protein, and fat consumption. Dyslipidemia was defined when one or more of the following abnormal lipid levels were observed: high cholesterol levels, high triglyceride levels, and low high-density lipoprotein cholesterol levels. Multivariate adjusted odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated using logistic regression models. After adjusting the confounding variables, in males, the OR of hypercholesterolemia was 1.87 (95% CI, 1.23-2.85; p for trend = 0.0017) and the OR of hypertriglyceridemia was 1.47 (95% CI, 1.04-2.06; p for trend = 0.0336), on comparing the highest and lowest quartiles of the LCD score. The animal-based LCD score showed a similar trend. The OR of hypercholesterolemia was 2.15 (95% CI, 1.41-3.29; p for trend = 0.0006) and the OR of hypertriglyceridemia was 1.51 (95% CI, 1.09-2.10; p for trend = 0.0156). However, there was no significant difference between plant-based LCD scores and dyslipidemia. In females, lipid profiles did not differ much among the quartiles of LCD scores-only the animal-based LCD score was statistically significant with hypercholesterolemia. The OR of hypercholesterolemia was 1.64 (95% CI, 1.06-2.55), on comparing the highest and lowest quartiles of the LCD score. In conclusion, a higher LCD score, indicating lower carbohydrate intake and higher fat intake, especially animal-based fat, was significantly associated with higher odds of hypercholesterolemia and hypertriglyceridemia in Chinese males. Future studies investigating the potential mechanisms by which macronutrient types and sex hormones affect lipid metabolism are required.


Pseudo-Temporal Analysis of Single-Cell RNA Sequencing Reveals Trans-Differentiation Potential of Greater Epithelial Ridge Cells Into Hair Cells During Postnatal Development of Cochlea in Rats.
The hair cells of the cochlea play a decisive role in the process of hearing damage and recovery, yet knowledge of their regeneration process is still limited. Greater epithelial ridge (GER) cells, a type of cell present during cochlear development that has the characteristics of a precursor sensory cell, disappear at the time of maturation of hearing development. Its development and evolution remain mysterious for many years. Here, we performed single-cell RNA sequencing to profile the gene expression landscapes of rats' cochlear basal membrane from P1, P7, and P14 and identified eight major subtypes of GER cells. Furthermore, single-cell trajectory analysis for GER cells and hair cells indicated that among the different subtypes of GER, four subtypes had transient cell proliferation after birth and could transdifferentiate into inner and outer hair cells, and two of them mainly transdifferentiated into inner hair cells. The other two subtypes eventually transdifferentiate into outer hair cells. Our study lays the groundwork for elucidating the mechanisms of the key regulatory genes and signaling pathways in the trans-differentiation of GER cell subtypes into hair cells and provides potential clues to understand hair cell regeneration.


Estimation of the 3D self-similarity parameter of trabecular bone from its 2D projection.
It has been shown that the analysis of two dimensional (2D) bone X-ray images based on the fractional Brownian motion (fBm) model is a good indicator for quantifying alterations in the three dimensional (3D) bone micro-architecture. However, this 2D measurement is not a direct assessment of the 3D bone properties. In this paper, we first show that S(3D), the self-similarity parameter of 3D fBm, is linked to S(2D), that of its 2D projection, by S(3D)=S(2D)-0.5. In the light of this theoretical result, we have experimentally examined whether this relation holds for trabecular bone. Twenty one specimens of trabecular bone were derived from frozen human femoral heads. They were digitized using a high resolution mu-CT. Their projections were simulated numerically by summing the data in the three orthogonal directions and both 3D and 2D self-similarity parameters were measured. Results show that the self-similarity of the 3D bone volumes and that of their projections are linked by the previous equation. This demonstrates that a simple projection provides 3D information about the bone structure. This information can be a valuable adjunct to the bone mineral density for the early diagnosis of osteoporosis.


Heritability estimates for ages at farrowing, rebreeding interval and litter traits in swine.
Data from three commercial herds of swine located in Santa Catarina State, Brazil, were used to estimate least-squares means, variance components and heritabilities for reproductive traits. A total of 663 Landrace and Large White gilts by 155 sires provided information on first farrowing and litter traits and records on 433 sows by 118 sires were available for second farrowing traits. Age at conception and at farrowing, number born, number born alive and first to second farrowing interval were analyzed. Landrace females were younger than Large White females at first and second conception and first and second farrowing (P less than .05). Gilts born during summer months were younger at first farrowing (P less than .05) than those born during winter. Sows weaning their first litter during the summer had longer gestation periods and longer weaning to conception and farrowing intervals than sows weaning their first litter during the winter (P less than .001). Least-squares means for age at first conception and farrowing and at second conception and farrowing were 273.5, 388.3, 437.0 and 551.8 d, respectively. Average weaning to conception and farrowing intervals were 22.0 and 173.7 d, respectively. Sire variance components were usually negative or equal to zero for first and second litter traits. This was also observed for dams in some cases.(ABSTRACT TRUNCATED AT 250 WORDS)