Cells of the fetomaternal interface: their role in the maintenance of viviparous pregnancy.
An immune system capable of discriminating between self and nonself evolved in nature long before the appearance of the viviparous mode of pregnancy, which brings maternal cells into a direct physical contact with genetically disparate cells of fetal origin. In the hemochorial type of placentation, the former include cells of the maternal immune system. This article briefly reviews the possible mechanisms that may protect the semiallogeneic conceptus in nature, with special reference to the role of the cells at the fetomaternal interface. We also present some new data on the antigenicity of pre- and postimplantation trophoblast cells and the immunobiology of decidual cells. Systemic changes in the maternal immune system appear to represent homeostatic responses to the presence of a semiallogeneic conceptus, unrelated to its protection; mechanisms for this protection must reside locally at the fetomaternal interface. We find that the lack of immunogenicity of the outer (trophoblast) cells of the preimplantation blastocyst can be explained by a transient disappearance of the major histocompatibility (MHC) antigens on their cell surface. However, following implantation and the formation of the placenta, class 1 MHC antigens reappear on certain classes of trophoblast cells, i.e., labyrinthine and spongiotrophoblast cells of the murine placenta. Similarly, cytotrophoblast cells of the early human placenta exhibit the presence of class 1 MHC antigens. An absence of class 2 MHC antigens despite the presence of class 1 antigens cannot entirely explain the lack of trophoblast immunogenicity. A local immunosuppression mediated by trophoblast cells themselves as well as maternal cells of hemopoietic origin in the decidua remain as a strong possibility. Typical decidual cells appear to play a central role in the maintenance of pregnancy because of their numerous functions: nutritive, endocrine, and immunoregulatory. Our studies reveal that they are descendants of bone-marrow-derived precursors, have unique surface markers recognizable with monoclonal antibodies nonreactive with other hemopoietic cell lineages, and have the ability to abrogate mixed lymphocyte reactions in vitro in a genetically unrestricted manner. Further studies directed at the cells of the fetomaternal interface should provide a better insight into the mode of survival of the nature's most commonplace allograft.


Head and neck amyloidosis: clinicopathological features and immunohistochemical analysis of 14 cases.
Amyloidosis is associated with or caused by amyloid deposition. These fibrillar proteins may be deposited extracellularly causing tissue damage or impairment. The aim of the study was to retrospectively review pathology archives in two oral diagnostic centers for cases fulfilling criteria of amyloidosis and to differentiate AA and AL types of amyloidosis. The clinicopathological features, alkaline Congo red staining, with and without pretreatment with potassium permanganate, and immunohistochemical (IHC) staining with anti-AA, anti-kappa (κ), and anti-lambda (λ) light chain antibodies were carried out and analyzed. The search identified 14 cases. Ten patients were women and four were men, with a mean age of 58 years. Eleven patients had systemic involvement by amyloidosis (associated either with multiple myeloma or plasma cell dyscrasia/monoclonal gammopathies), while three presented the localized type, one of them associated with plasmacytoma. All cases showed positivity for κ or λ light chains (AL-amyloid) and presented resistance to the potassium permanganate pretreatment. Our results show that the head and neck region is preferentially affected by systemic AL-amyloidosis, usually associated with plasma cell dyscrasia. Interestingly, two cases affected by inflammatory rheumatic diseases presented AL-amyloid deposition. Moreover, even after pretreatment with potassium permanganate, which was helpful in highlighting the presence of AL-amyloid, in agreement with the IHC findings, clinical classifications should be carefully made in systemic amyloidosis.


Molecular mechanism of doxorubicin-induced cardiomyopathy - An update.
Doxorubicin is utilized for anti-neoplastic treatment for several decades. The utility of this drug is limited due to its side effects. Generally, doxorubicin toxicity is originated from the myocardium and then other organs are also ruined. The mechanism of doxorubicin is intercalated with the DNA and inhibits topoisomerase 2. There are various signalling mechanisms involved in doxorubicin cardiotoxicity. First and foremost, the doxorubicin-induced cardiotoxicity is due to oxidative stress. Cardiac mitochondrial damage is supposed after few hours following the revelation of doxorubicin. This has led important new uses for the mechanism of doxorubicin-induced cardiotoxicity and novel avenues of investigation to determine better pharmacotherapies and interventions for the impediment of cardiotoxicity. The idea of this review is to bring up to date the recent findings of the mechanism of doxorubicin cardiomyopathies such as calcium dysregulation, endoplasmic reticulum stress, impairment of progenitor cells, activation of immune, ubiquitous system and some other parameters.


Nedaplatin-Induced Arrhythmia: Retrospective Analysis of Three Cases.
Nedaplatin (NDP) is a second-generation platinum derivative that was developed in Japan. Nowadays, it is being widely used in the management of lung cancer, esophageal cancer, head and neck cancers, especially when cisplatin and carboplatin cannot be tolerated or show drug resistance. To the best of our knowledge, there are few reported cases of NDP-induced bradycardia in the relevant medical literature. The current report presents three patients treated with NDP chemotherapy-induced serious arrhythmias. The three cases developed sinus tachycardia and atrial premature beats, complete left bundle branch block, and bigeminy ventricular premature contraction, in the second, sixth and second cycle, respectively. No one died of cardiac toxicity. These were treated with dexamethasone, 5 mg intravenous injection and diphenhydramine 20 mg, intramuscular injection. The heart rhythm returned to normal in 30 minutes, a day, and four days, respectively.


The Changing Landscape in Treatment of Cystic Lesions of the Jaws.
Cystic lesions of the jaw are common pathologies of chronic swelling of the jaw in oral and maxillofacial regions. Different treatment modalities have been described in the literature. However, the existence and proper treatment of these cysts remains a contentious topic. The aims of this review were to discuss the complexity of various surgical treatment and as factors with potential to influence outcome treatment. Finally, a practical and a rational clinical guideline for the management of such lesions have been suggested. A literature search without language limitation was performed in 2018 using MEDLINE, PubMed, Scopus, and Embase. Keywords for the search included the following terms: jaws cyst, cystic lesions, odontogenic cysts, cystic tumors, pseudocysts, treatments, therapy, wound healing, bone regeneration, and teeth involved cysts. Prospective or retrospective clinical studies with a sample size of n ≥ 5 were evaluated and included in this review. The exclusion criteria were studies with unclear reporting of the treatment applied or outcome, nonhuman studies, case reports, letters, preface, comments, and cystic lesions associated to syndrome. After the full reading, 30 articles were included in the quantitative synthesis for the review. No meta-analysis could be performed due to the heterogeneity of the studies included. Clinical radiographic images were presented to illustrate the principles of some surgical treatments. Conservative surgery with primary closure defect (less than 4 cm) remains an initial approach, which reduces the morbidity of aggressive surgeries and obtains the complete bone healing before 24 months of postoperative. Marsupialization is considered as the most common option for the treatment of large cystic lesions when cases are carefully selected. Evocyst is an attractive new technique of obtaining complete bone defect healing within <3 months.


[Contrast analysis of different sagittal split ramus osteotomy methods in correcting mandibular prognathism].
To explore the indication, advantage and disadvantage of modified or classical technique of intraoral sagittal split ramus osteotomy (SSRO) for correction of mandibular prognathism. From January 1997 to January 2005, 95 patients suffering from mandibular prognathism or accompanied by other deformities were treated with modified or classical technique of intraoral SSRO. Of 95 cases, there were 34 males and 61 females, aging 15 to 44 years, including 53 cases of single mandibular prognathism, 28 cases accompanied with mandibular deviation, 11 cases accompanied with maxillary retrognathism, 2 cases accompanied with glossacele and 1 case accompanied with malar protrusion. X-ray cephalometry showed: sella-nasion-A point (SNA) 80-83 degrees, sella-nasion-B point (SNB) 80-84 degrees, A point-nasion-B point (ANB)--3-1 degrees. Forty-three cases were corrected by modified SSRO and 52 cases by classical SSRO. The face appearance and dental articulation of all the patients were improved greatly. In patients by classical SSRO, disorder of local sensibility occurred in 9 cases, mandibular fracture during the cleavage of the ascending ramus in 1 case, significant bleeding in 1 case, postoperative infection in 1 case and postoperative relapse in 3 cases. In patients by modified SSRO, disorder of local sensibility occurred in 2 cases and postoperative relapse in 1 case; no mandibular fracture, significant bleeding, postoperative infection and other complications occurred. With a follow-up of 3 months to 7 years, X-ray cephalometry showed SNA 81-83 degrees, SNB 78-81 degrees and ANB 1-4 degrees. Modified SSRO is an ideal method of correcting mandibular prognathism, especially severer mandibular prognathism accompanied by mandible deviation deformity.


Dynamics of respiratory response to sinusoidal work load in humans.
The present study was undertaken to investigate possible distortion in responses of respiratory variables including O2 uptake (VO2), CO2 output (VCO2), and ventilation (VE) to sinusoidal work load, and to find out whether the conventional transfer models were applicable to analyze the dynamics of these variables. Six healthy subjects performed exercise for 32 min on a bicycle ergometer with electro-magnetic braking. The work load was varied sinusoidally between 30 W and 60% of maximum O2 uptake (VO2max) during periods from 1 to 16 min. The respiratory variables were measured on a breath-by-breath basis with a mass spectrometer and a computer system. The responses of VO2, VCO2, and VE to sinusoidal work load were not completely sinusoidal in form but were somewhat distorted, forming saw-tooth waves with steeper down-slopes during periods of 4-16 min, but this distortion was not observed at 1 min or 2 min periods. However, the results could be approximately described by a first-order model without or with time delay. Time constants of the first-order model without time delay were 46 sec for VO2, 62 sec for VCO2, and 73 sec for VE, respectively. We also found a close relationship between the time constants of VO2 and VCO2 and VO2max. These results suggested that exponential functions may be applied and are expected to yield valid results in assessing physical fitness, although the control of ventilatory and gas exchange in exercise does show non-linear characteristics.


Pronator teres transfer to correct pronation deformity of the forearm after an obstetrical brachial plexus injury.
A pronation deformity of the forearm following an obstetric brachial plexus injury causes functional and cosmetic disability. We evaluated the results of pronator teres transfer to correct their deformity in 14 children treated over a period of four years. The mean age at surgery was 7.6 years (5 to 15). The indication for surgery in each case was impairment of active supination in a forearm that could be passively supinated provided that there was no medial contracture of the shoulder and normal function of the hand. The median follow-up was 20.4 months (8 to 42). No patient was lost to follow-up. Qualitative results were also assessed. The median active supination improved from 5 degrees (0 degrees to 10 degrees ) to 75 degrees (70 degrees to 80 degrees ) with no loss of pronation. A passively correctible pronation contracture can be corrected safely and effectively by the transfer of pronator teres.


Breakthrough Infection With Severe Acute Respiratory Syndrome Coronavirus 2 Among Healthcare Workers in Delhi: A Single-Institution Study.
Introduction This study aimed to determine the breakthrough infection rate of coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus 2 {SARS-CoV-2}) infection in healthcare workers (HCWs) vaccinated with either BBV152 or AZD1222 (ChAdOx1-S) vaccine. Methods A cross-sectional analysis was conducted at a medical college and hospital complex in Delhi, India, through telephonic interviews among HCWs who had received at least one dose of a COVID-19 vaccine during January-March 2021. Breakthrough infections were operationally defined as the occurrence of COVID-19 infection ≥14 days after administration of two doses of either COVID-19 vaccine. Data were entered in Epidata 3.1 (Odense, Denmark: EpiData Association) (single entered) and analyzed with IBM SPSS version 25 (Armonk, NY: IBM Corp.). A p-value < 0.05 was considered statistically significant. Results We enrolled 325 HCWs with a mean (SD) age of 29.1 (9.9) years including 211 (64.9%) males and 114 (35.1%) females. A total of 37 (13.3%, 95% CI 9.8, 17.7) COVID-19 breakthrough infections were observed in the HCWs. Additionally, 20 (6.1%) non-breakthrough infections were reported in the HCWs who were vaccinated with at least a single dose of a COVID-19 vaccine, or both doses, but prior to 14 days since the administration of the second dose. Most breakthrough infections were mild without needing supplemental oxygen for recovery. Conclusion Nearly one in seven HCWs experienced a COVID-19 breakthrough infection in the present study. A history of SARS-CoV-2 natural infection followed by at least one dose of COVID-19 vaccination was associated with significant protection against breakthrough infections.


Fluorescent S1 nuclease assay utilizing exponential strand displacement amplification.
We herein devise a simple and label-free strategy to determine S1 nuclease activity by exploiting the target-induced inhibition of exponential strand displacement amplification (eSDA). In principle, a DNA probe that is designed to produce a large amount of duplexes through a process of eSDA, is degraded by the catalytic activity of S1 nuclease. This reaction blocks the initiation of eSDA, leading to the quite-reduced fluorescence of a double-stranded DNA specific fluorescent dye, SYBR Green I compared to the one in the absence of S1 nuclease. With this simple but novel approach, the S1 nuclease activity was selectively assayed with the high sensitivity. In addition, this system was successfully demonstrated to possess the capability to screen potential inhibitors against S1 nuclease.


A study of the role of DIO1 and DIO2 polymorphism in thyroid cancer and drug response to therapy in the Saudi population.
Deiodinases comprise a group of selenoproteins that regulate the bioavailability of active thyroid hormones (TH) in a time and tissue specific fashion. They increase the hormonal activity by metabolizing their inactive precursors to active forms or terminate their activity by deactivating active hormones. The role of the deiodinase (DIO) gene polymorphisms in thyroid cancer is not fully understood yet. This study evaluated the potential association of the DIO1 and DIO2 genes with differentiated thyroid cancer and differential thyroxine dose requirement in thyroidectomized patients in a Saudi cohort. We selected four variants (one DIO1 and three DIO2) for the association studies using Taqman assays in 507 DTC patients undergoing treatment with thyroxin against 560 disease-free individual, all of Saudi Arab origin. None of the studied variants was linked to differentiated thyroid cancer. The rs1388378_G > T was initially linked to thyroxine dose requirement (p = 0.035) when all patients were considered together, but this association was lost when the patients were classified into either near suppressed (0.1 ≤ TSH < 0.5) or suppressed (TSH < 0.1) TSH group. Although the results suggest only a weak relationship with differentiated thyroid cancer, they strongly indicate that the DIO2 polymorphism influences the hormonal dose requirement in patients undergoing treatment with thyroxine. This probably points to a distinction in the way this gene influences disease as compared to therapy thereof.


[Unilateral myelinated nerve fibers associated with myopia or amblyopia].
There are described a number of 9 clinical cases with unilateral myelinated nerve fibers, associated with myopia or amblyopia. Four cases developed extended myelinated areas, anisometropia with increased values, accentuated amblyopia and macular changes. Patients underwent treatment for amblyopia through correction with spectacles lenses and the occlusion of the congenerous eye. The obtained functional results differentiated the casemix in two groups: with therapeutic failure, 4 cases, characterized by extended myelination, anisometropia with an average of over -10 diopters and macular changes. with therapeutic success, 5 cases, characterized by reduced myelination, anisometropia with an average of over -4 diopters and normal maculae. It has been found a significantly statistical difference between the two groups as regarding the value of the anisometropia. However, the macular aspect has been an important factor in order the therapeutic effect to succeed. This clinical syndrome is differentiated from the unilateral simple myopia with amblyopia and from the myelinated nerve fibers without myopia or amblyopia.


[Analysis on the tendency of practical dust exposure year and the out-of-dust rate among coalminers].
It is important to study the practical dust exposure year and out-of-dust rate for the evaluation of dust level and to predict pneumoconiosis incidence in coal miners. A Retrospective Cohort Study was carried out on the calculation of practical dust exposure year and the out-of-dust rate among coal miners employed during 1958-1988 in a mine. The results showed that job variety had a strong effect on dust exposure year and that out-of-dust rate beared relationship to the years of employment. It can be estimated that the percentage of coalminers who were employed in 1975-1979 with dust exposure year reached 20 years would be less than 30%, and that those being employed after 1980 would be even lesser.


Edge behaviour in a minute parasitic wasp.
1. Changes in the density of an organism near a boundary elements (edge effects) are often thought to be generated by changes in movement behaviour, but in most cases the mechanism underlying these effects is unknown. 2. We quantified the movement behaviour of a minute parasitic wasp, Anagrus columbi, in relation to edges in its habitat. This wasp attacks eggs of the planthopper Prokelisia crocea, which inhabits a wet prairie ecosystem composed of patches of its host plant prairie cordgrass (Spartina pectinata) interspersed within a matrix of mudflat, smooth brome (Bromus inermis) and native grasses. Two edge types are common in this system, cordgrass-mudflat and cordgrass-brome. 3. We conducted mark-recapture experiments in which wasps were released at the cordgrass-matrix edge and 50 cm within cordgrass or matrix, for both edge types. The marked wasps were recaptured using a grid of sticky traps. We fitted an advection-diffusion model to these data, yielding estimates of the diffusion rate and advection coefficient for cordgrass and matrix, for each release position and edge type. 4. The spatial distribution of wasps was well-described by the advection-diffusion model. The pattern suggests that marked wasps strongly biased their movements towards the edge when released in matrix, and to a lesser extent when released in cordgrass, while edge releases showed little bias. The advection coefficients were similar for the two edge types, as were the diffusion rates for the three substrates (cordgrass, brome, mudflat). The diffusive and advective components of movement were of comparable magnitude for matrix and cordgrass releases, suggesting equal amounts of directed and random movement. 5. Our results suggest the wasps are attracted to cordgrass patches across short distances, and that bias in their movements may concentrate them at the patch edge. Their edge behaviour is qualitatively different from that of the host insect. 6. The methodology described here could be readily adapted to other systems, where direct observations of movement are difficult but mark-recapture studies are feasible.


Development and content validation of the Wheelchair Use Confidence Scale: a mixed-methods study.
Confidence in one's ability to perform a given task can be a stronger predictor of performance than skill itself. There are currently no measures to assess confidence with manual wheelchair use. The objective of this study was to develop and assess the content validity of the Wheelchair Use Confidence Scale (WheelCon-M). A two-phase mixed-methods design was used. Semi-structured interviews were conducted to generate items, followed by a Delphi survey for item selection. Persons who use a wheelchair, health care professionals, and researchers participated in both phases of the study. An 84-item WheelCon-M was developed based on the qualitative data. After the Delphi survey, a final 62-item WheelCon-M was composed of the following six areas (number of items per area): Negotiating the Physical Environment (33 items), Activities Performed using a Manual Wheelchair (11 items), Knowledge and Problem Solving (6 items), Advocacy (4 items), Managing Social Situations (5 items) and Managing Emotions (3 items). This article reports the development and content validation of the WheelCon-M. As a scale to measure confidence with wheelchair use was not available prior to this work, clinicians now have a method of identifying individuals who have low confidence with wheelchair use.


Platelet Activation and Inflammation in Patients with Papillary Thyroid Cancer.
The primary endpoint was to analyze the preoperatory inflammatory markers and platelet indices in papillary thyroid cancer (PTC) patients compared with patients with benign thyroid pathology. The secondary endpoints were to analyze the relationship between these markers and the pathological features of PTC and to compare their pre- and postoperative levels in PTC patients. In this retrospective case-control study, we analyzed the files of 1183 patients submitted to thyroidectomy between January 2012 and December 2018. A total of 234 patients with PTC (mean age 51.54 ± 13.10 years, 84.6% females) were compared with an age-, gender- and BMI-matched control group of 108 patients with histologic benign thyroid disorders. PTC patients had higher platelet count (PLT) (p = 0.011), plateletcrit (PCT) (p = 0.006), neutrophil (p = 0.022) and fibrinogen (p = 0.005) levels. Subgroup analysis showed that PTC females had higher PLT (p = 0.006), PCT (p < 0.001) and erythrocyte sedimentation rate (ESR) (p = 0.005), while males had higher neutrophil (p = 0.040) levels. Papillary thyroid cancer patients under 55 years had higher PLT (p < 0.001) and PCT (p = 0.010), while patients over 55 years had higher mean platelet volume (p = 0.032), neutrophil-to-lymphocyte ratio (p = 0.013), ESR (p = 0.005) and fibrinogen (p = 0.019) levels. Preoperative values for platelet indices and inflammatory markers were similar to the postoperative determinations in PTC patients. Fibrinogen (AUROC = 0.602, p = 0.02; cut-off = 327.5 mg/dL, Se = 53.8%, Sp = 62.9%) and PLT (AUROC = 0.584, p = 0.012; cut-off = 223.5 × 103/mm3, Se = 73.1%, Sp = 42.6%) were independent predictors of the presence of PTC. Our data show that fibrinogen and platelet count could be promising, inexpensive, independent predictors for the presence of PTC when compared with benign thyroid disorders.


Implementing a clinically focused advancement system. One institution's experience.
Clinical ladders were designed to recognize, reward, and retain professional nurses who chose to remain in direct clinical practice. One institution implemented a clinically focused advancement system that addresses many of the pitfalls that have historically caused clinical ladders to fail. The authors describe unique features of the advancement system, along with the process for advancement, budgetary considerations, and transition to the new advancement system.


pH-dependent promotion of phospholipid flip-flop by the KcsA potassium channel.
KcsA is a pH-dependent potassium channel that is activated at acidic pH. The channel undergoes global conformational changes upon activation. We hypothesized that the open-close conformational changes of the transmem brane region could promote the flip-flop of phosphoiipids. Based on this hypothesis, we measured the flip-flop ofNBD-labeled phospholipids in KcsA-incorporated proteoliposomes. Both flip and flop rates of ~NBD-PC were significantly enhanced in the presence of KcsA and were several times higher at pH 4.0 than at pH 7.4, suggesting that KcsA promotes the phospholipid flip in a conformation-dependent manner. Phospholipids were nonselectively flipped with respect to the glycerophospholipid structure. In the active state of KcsA channel,tetrabutylammonium locks the channel in the open conformation at acidic pH; however, it did not alter the fliprate of CGNBD-PC. Thus, the open-close transition of the transmembrane region did not affect the flip-flop of phospholipids. In addition, the KcsA mutant that lacked anN-terminal amphipathic helix (MO-helix) was found to show reduced ability to fl ip C6NBD-phospholipids at acidic pH. The closed conformation is stabilized in the absence of MO-heli x, and thus the attenuated flip could be explained by the reduced prevalence of the open conformation.These results suggest that the open conformation of KcsA can disturb the bilayer integrity and facilitate the flip-flop of phospholipids.


Impact of the Inferior Right Hepatic Veins on Right Liver Lobe Regeneration in Living-Donor Liver Transplant: 3-Dimensional Computed Tomography Scan Analyses in Donors and Recipients.
The presence of an inferior right hepatic vein significantly modifies the outflow pattern of the right liver and may have an impact on graft regeneration. Study patients were donors and recipients with 3-dimensional computed tomography scan simulation. We studied the physiologic impact of the inferior right hepatic veins on right liver regeneration in donors of left lobe grafts (step1; n = 60 patients) and the efficacy of a inferior right hepatic vein reconstruction policy based on a vessel caliber > 5 mm criteria in recipients of right liver grafts (step 2; n = 38 patients). In step 1, the regeneration rate at 1 month was comparable between future liver remnants with inferior right hepatic vein (regeneration rate of 28.3%) and without inferior right hepatic vein (regeneration rate of 30.2%). In step 2, at 3 months after living-donor liver transplant, we observed no significant differences in regeneration rates among grafts anatomically without an inferior right hepatic vein (regeneration rate of 60.7%), grafts with an inferior right hepatic vein but no reconstruction (regeneration rate of 64.9%), and grafts with an inferior right hepatic vein and its reconstruction (regeneration rate of 68.1%). Within the latter subgroup, grafts with a dominant inferior right hepatic vein showed a greater regeneration of the anterior sector with inversion of the anterior-to-posterior sector regeneration ratio compared with right hepatic vein-dominant grafts (inferior right hepatic vein-dominant vs right hepatic vein-dominant showed anterior sector regeneration rates of 85.7% vs 52.1%; P = .02; anterior/posterior sector regeneration ratio was 2.3 vs 0.6, respectively; P = .04). The reconstruction policy for inferior right hepatic vein with caliber > 5 mm is effective but should be implemented with computed tomography scan simulation. Right lobe grafts with a dominant inferior right hepatic vein are at higher risk of impaired regeneration due to expected large volumes of hepatic venous congestion if the middle hepatic veins tributaries or the inferior right hepatic veins are not reconstructed and an increased rate of right hepatic vein complications.


A novel approach to estimate the German-wide incidence of testicular cancer.
Currently, only 7 out of 16 Federal States of Germany provide testicular cancer incidence rates with an estimated completeness of at least 90% which complicates the regional comparison of incidence rates. The aim of this study was to provide a novel approach to estimate the testicular cancer incidence in Germany by using nationwide hospitalization data. We used the nationwide hospitalization data (DRG statistics) of the years 2005-2006 including 16,6 million hospitalizations among men. We identified incident testicular cancer cases by the combination of a diagnosis of testicular cancer and an orchiectomy during the same hospitalization and estimated the age-specific and age-standardized (World Standard Population) incidence of testicular cancer across Federal States. We also analyzed available cancer registry data from 2005 to 2006. A total of 8544 hospitalizations indicated incident testicular cancer cases in 2005-2006. The nationwide crude incidence rate of testicular cancer was 10,6 per 100.000 person-years. The ratio of the number of registered cases (cancer registry) to the estimated number of cases based on the hospitalization statistics ranged between 79% and 100%. There was only little variation of the age-standardized DRG-based incidence estimates across Federal States (range: 8,2-10,6 per 100.000 person-years). We provided testicular cancer incidence estimates for each of the 16 Federal States of Germany based on hospitalization data for the first time. The low within-population incidence variability in Germany and high between-population incidence variability in Europe may indicate that ecologic factors play a causal role in the European variation of testicular cancer.


Recent innovations in edible and/or biodegradable packaging materials.
Certain newly discovered characteristics of natural biopolymers should make them a choice material to be used for different types of wrappings and films. Edible and/or biodegradable packagings produced from agricultural origin macromolecules provide a supplementary and sometimes essential means to control physiological, microbiological, and physicochemical changes in food products. This is accomplished (i) by controlling mass transfers between food product and ambient atmosphere or between components in heterogeneous food product, and (iii) by modifying and controlling food surface conditions (pH, level of specific functional agents, slow release of flavour compounds), it should be stressed that the material characteristics (polysaccharide, protein, or lipid, plasticized or not, chemically modified or not, used alone or in combination) and the fabrication procedures (casting of a film-forming solution, thermoforming) must be adapted to each specific food product and usage condition (relative humidity, temperature). Some potential uses of these materials (e.g. wrapping of various fabricated foods; protection of fruits and vegetables by control of maturation; protection of meat and fish; control of internal moisture transfer in pizzas), which are hinged on film properties (e.g. organoleptic, mechanical, gas and solute barrier) are described with examples.


Reduction of experimental colitis in the rat by inhibitors of glycogen synthase kinase-3beta.
The effects of the inhibitors of glycogen synthase kinase-3beta (GSK-3beta), TDZD-8 and SB 415286, which can substantially reduce the systemic inflammation associated with endotoxic shock in vivo, have now been investigated on the acute colitis provoked by trinitrobenzene sulphonic acid (TNBS) in the rat. Administration of the GSK-3beta inhibitor TDZD-8 (0.1, 0.33 or 1.0 mg kg-1, s.c., b.i.d., for 3 days) caused a dose-dependent reduction in the colonic inflammation induced by intracolonic TNBS assessed after 3 days, both as the area of macroscopic involvement and as a score using 0-10 scale. Likewise, following administration of the GSK-3beta inhibitor SB 415286 (0.1, 0.33 or 1.0 mg kg-1, s.c., b.i.d., for 3 days), the extent and degree of the TNBS-provoked colonic inflammation was reduced. Administration of either TDZD-8 or SB 415286 reduced the fall in body weight following challenge with TNBS at each dose level studied. The increase in myeloperoxidase activity, an index of neutrophil infiltration into the TNBS-induced inflamed colon, was significantly inhibited by both TDZD-8 and SB 415286 at each dose level. The increase in the levels of the proinflammatory cytokine, TNF-alpha, in the inflamed colon was also significantly inhibited by either compound at the highest doses evaluated. The elevated levels of the transcription factor NF-kappaB subunit p65, as determined by Western blot in the nuclear extracts from the TNBS-provoked inflamed colonic tissue, were dose-dependently reduced by TDZD-8 or SB 415286 treatment. These findings demonstrate that two chemically distinct selective inhibitors of the activity of GSK-3beta reduce the inflammation and tissue injury in a rat model of acute colitis. The mechanisms underlying this anti-inflammatory action may be related to downregulation of NF-kappaB activity, involved in the generation of proinflammatory mediators.


New avenues of sepsis research: obtaining perspective by analyzing and comparing SSCG 2021 and J-SSCG 2020.
Recently, revisions of two sepsis guidelines, namely, the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 and the Surviving Sepsis Campaign Guidelines 2021, were published. Although both guidelines were created in accordance with the Grading of Recommendations, Assessment, Development and Evaluation approach, the evidence-to-decision tables differed between them. In addition, certain recommendations may differ between these guidelines for similar clinical questions because of differences in the "PICO" criteria. Other differences in recommendations between the two guidelines are due to unclear evidence, and these ambiguities may provide the basis for further sepsis research. We hope that these two guidelines will contribute to the creation of new clinical evidence in addition to supporting treatment of patients with sepsis.


Clinical spectrum of AIFM1-associated disease in an Irish family, from mild neuropathy to severe cerebellar ataxia with colour blindness.
Mutations in apoptosis-inducing factor mitochondrion-associated-1 (AIFM1) cause X-linked peripheral neuropathy (Cowchock syndrome, CMT4X); however, more recently a cerebellar presentation has been described. We describe a large Irish family with seven affected males. They presented with a variable age of onset, 18 months to 39 years of age. All developed variably present sensorineural deafness, peripheral neuropathy, cerebellar ataxia, and pyramidal involvement. In addition, three had colour vision deficiency. Scale for the assessment and rating of ataxia ranged 2 to 23/40, while Charcot-Marie-Tooth neuropathy score 2 varied between 7 and 13/36. All individuals had normal cognitive assessment. Neurophysiology demonstrated length-dependent large-fibre sensorimotor axonal neuropathy, with particular involvement of superficial radial sensory responses. Brain imaging, performed in four, revealed varying extent of cerebellar atrophy, and white matter changes in one. Optical coherence tomography was abnormal in one, who had unrelated eye pathology. Four obligate female carriers were assessed clinically, two of them neurophysiologically; all were unaffected. Whole genome sequencing demonstrated a previously reported hemizygous AIFM1 mutation. Analysis for mutations in other genes associated with colour deficiency was negative. AIFM1-associated phenotype in this family demonstrated significant variability. To our knowledge, this is the first report of AIFM1-associated colour blindness. Superficial radial nerve was particularly affected neurophysiologically, which could represent a phenotypic marker towards this specific genetic diagnosis.


Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation.
Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions.


Childhood leukemia around French nuclear power plants--the Geocap study, 2002-2007.
The aim of this work is to study the risk of childhood acute leukemia (AL) around French nuclear power plants (NPPs). The nationwide Geocap case-control study included the 2,753 cases diagnosed in mainland France over 2002-2007 and 30,000 contemporaneous population controls. The last addresses were geocoded and located around the 19 NPPs. The study used distance to NPPs and a dose-based geographic zoning (DBGZ), based on the estimated dose to bone marrow related to NPP gaseous discharges. An odds ratio (OR) of 1.9 [1.0-3.3], based on 14 cases, was evidenced for children living within 5 km of NPPs compared to those living 20 km or further away, and a very similar association was observed in the concomitant incidence study (standardized incidence ratio (SIR)=1.9 [1.0-3.2]). These results were similar for all the 5-year-age groups. They persisted after stratification for several contextual characteristics of the municipalities of residence. Conversely, using the DBGZ resulted in OR and SIR close to one in all of the dose categories. There was no increase in AL incidence over 1990-2001 and over the entire 1990-2007 period. The results suggest a possible excess risk of AL in the close vicinity of French NPPs in 2002-2007. The absence of any association with the DBGZ may indicate that the association is not explained by NPP gaseous discharges. Overall, the findings call for investigation for potential risk factors related to the vicinity of NPP and collaborative analysis of multisite studies conducted in various countries.


Dermatobia hominis: Small Migrants Hidden in Your Skin.
Myiasis is a parasitic infestation of vertebrate animal tissues due to maggots of two-winged flies (Diptera) that feed on living or necrotic tissue. Dermatobia hominis occurs widely in tropical parts of Latin America; it is the most common cause of furuncular myiasis in this region. The continuous increase in international travel has increased the possibility of observing this pathology outside endemic countries, especially in travelers returning from the tropics. If clinicians are aware of the possibility of the disease and its treatment options, this dermatosis can be easily managed. However, diagnostic delay is very common because the disease is often misdiagnosed as a bacterial skin infection. Here, we report 2 cases of furuncular myiasis caused by D. hominis in travelers returning to Italy from Latin America. Surgical and noninvasive treatment approaches are also described.


Fabrication and evaluation of a chitin whisker/poly(L-lactide) composite scaffold by the direct trisolvent-ink writing method for bone tissue engineering.
Although poly(l-lactide) (PLLA) based porous scaffolds have been widely fabricated through 3D printing, their poor mechanical properties and osteogenic activity still do not meet the needs of bone tissue repair. Herein, chitin whiskers (CHWs), having outstanding mechanical properties, excellent cell affinity, osteogenic activity, etc. were designed to introduce into the PLLA matrix. Moreover, a trisolvent system, including dichloromethane (DCM), 2-butoxyethanlol (2-Bu) and dibutyl phthalate (DBP), instead of a single solvent system of DCM was chosen to prepare CHW/PLLA (CP) composite inks. Then, the CP porous composite scaffolds were further fabricated via the direct ink writing method. The as-printed CP composite scaffolds have good 3D porous structures with a pore size of 400 ± 14 μm and a porosity of 80 ± 5%. Compared with the pure PLLA scaffold, the CP composite scaffolds showed significantly superior hydrophilicity and compression performance, and also were more conducive to cell adhesion, proliferation, and up-regulating alkaline phosphate activity and calcium deposition due to the presence of CHWs. Moreover, these promoting effects of CHWs are positively related to the content of the whiskers in the range of 0-20 wt%. However, as the content of CHWs further increased to 40 wt%, the compression performance, cell affinity and osteogenic activity of the corresponding 40%CP composite scaffold decreased, which may be attributed to the different microstructure of the scaffold from other composite scaffolds. Interestingly, compared with these scaffolds containing a lower mass content of CHWs, only the 40%CP composite scaffold exhibited significant anti-inflammatory properties. These robust CP composite scaffolds offer a new route for bone tissue engineering application.


Patients with special health care needs in pediatric dental practices.
The objective of this study was to determine the involvement of pediatric dentists in practice in managing patients with special health care needs (SCHN) upon completion of training. A questionnaire was developed, pilot tested, modified and sent to a randomly selected sample of 950 pediatric dentists in practice who were active and fellow members of the American Academy of Pediatric Dentistry. Fifty-one percent of the dentists responded. The majority were males between the ages of 41 and 50 years. Most practiced in communities with over 500,000 citizens. Most were trained in hospital-based programs, and 84% reported comprehensive didactic courses on SHCN patients during training. SCHN patients were routinely appointed in an integrated schedule in their practices. Seventy-one percent of responders continue to follow the patients after 21 years of age. Most had buildings and offices that were handicapped accessible. Patient profiles remained similar since initiating private practice with notable increases reported in the new and recall patients and patients with complicated medical histories categories. The results of this survey demonstrate the continuing involvement of pediatric dentists in private practice in scheduling and treating patients with special health care needs after the completion of training.


[Development of the concept of «lean polyclinics»].
The article considers the first results of the Federal priority health care project that began in 2018 in Russia, aimed at organizing a new model of medical care. The mechanism of operation of a perfect polyclinic from the point of view of lean production is formed and developed thanks to management decisions based on the principles of lean production, allowing to increase the efficiency of the health care system. Definition of technology "lean clinic", using basic tools and structuring of losses in the field of medicine, according to the methodology of lean production, along with the generalization of positive foreign experience of introduction of technologies of lean production in health and its adaptation in Russia, will create a comfortable environment for doctors, medical staff and patients. The article presents statistical and analytical data on the regional practice of implementing the concept of "lean polyclinic", as well as expert assessments that allow us to draw conclusions about the progress of the project.


Cocaine and cigarettes: a comparison of risks.
In order to provide additional data and perspective to current clinical, policy, and legal debates surrounding the prenatal use of cocaine in the USA, a retrospective cohort study was conducted to examine effects of cocaine on selected perinatal outcomes, and to compare the relative risks of adverse perinatal outcomes among users of cocaine and users of cigarettes. Using data from a large urban perinatal registry, relative risks of selected perinatal outcomes were determined for maternal cocaine users who were non-smokers of cigarettes, and used no marijuana, heroin, amphetamines, or alcohol (n = 64), and for cigarette smokers who do not use illicit drugs or alcohol during pregnancy (n = 3209). When compared with women with no recorded prenatal exposure to drugs or cigarettes (n = 13,043), cocaine users had higher risks than smokers for the following adverse outcomes: low birthweight [Relative Risk (RR) 5.3, 95% Confidence Interval (CI) 3.0-9.3], small-for-gestational age (SGA) [RR 4.2, 95% CI 2.4-7.3], prematurity [RR 4.0, 95% CI 2.3-7.0], abruptio placentae [RR 10.0, 95% CI 3.5-29.0], placenta praevia [RR = 2.4, 95% CI 0.3-17.8] and perinatal death [RR = 5.3, 95% CI 1.9-15.2]. Smokers who did not use any drugs experienced most of the same adverse perinatal outcomes as cocaine users, but the magnitude of risk was greater in cocaine users than in smokers for all outcomes. However, given the greater numbers of cigarette smokers than cocaine users in the population the numbers of infants in the population suffering these adverse outcomes is likely to be greater among offspring of cigarette smokers. The data support the current concern about the risk of cocaine, and current efforts to provide treatment to pregnant cocaine users. The data also underline the continued substantial risks of cigarette smoking to large numbers of pregnant women.


Age-related behavioral and ultrastructural changes in the rat amygdala.
Although the relationships between brain structure and emotions may alter across the life span, this relationship is of particular importance during aging when significant alterations in emotions may be manifested. Understanding the structural-behavioral relationship could not only provide a neurobiological basis of these changes, but could also suggest potential intervention. Since anxiety is commonly observed in aging population, we undertook this study to determine the extent of this behavioral manifestations as well as the associated ultrastructural changes in the amygdala. Rats of various age groups, adolescent, adult, and aged were tested for anxiety-like behavior and the ultrastructure/presynaptic architecture of the central nucleus of amygdala (CNA) were evaluated using transmission electron microscopy (EM). Aged rats were consistently more anxious than the other groups as evidenced by their scores in the elevated plus maze. Morphometric EM analysis of axodendritic synapses revealed that the aged rats had a lower presynaptic area as well as number of synapses, but unexpectedly a higher number of presynaptic mitochondria in CNA. Since presynaptic mitochondria are known to provide the energy for neurotransmission, it may be concluded that compensatory mechanisms are still operational during aging, and hence, may be a target for therapeutic intervention at this stage of life span.


Combining FORGE Score and Histopathological Diagnostic Criteria of Atypical Meningioma Enables Risk Stratification of Tumor Progression.
More than 50% of atypical meningiomas regrow within 5 years after surgery. FORGE score is a newly created tool to estimate the MIB-1 index in cranial meningiomas. In this investigation, we aimed to assess the predictive value of the FORGE score in combination with major diagnostic criteria of atypical meningioma (brain invasion, mitotic count ≥ 4) regarding recurrence in atypical meningiomas. We included patients operated on primary atypical meningiomas in our center from 2011 to 2019. The study included 71 patients (58% women, median age 63 years). ROC curves revealed a superiority of FORGE score combined with histopathological diagnostic criteria of atypical meningioma (AT-FORGE) in the prediction of tumor progression compared to FORGE score only (AUC: 0.72; 95% CI: 0.54-0.91, cut-off: ≥5/<5, sensitivity: 75%, specificity: 78%). Patients with an AT-FORGE score ≥ 5 had a shorter time to tumor progression (32.8 vs. 71.4 months, p < 0.001) in the univariable analysis. Multivariable cox regression analysis revealed significant predictive value of Simpson grade > II, presence of multiple meningiomas and AT-FORGE score ≥ 5 for tumor progression. The combination of histopathological diagnostic criteria for atypical meningioma with FORGE score might facilitate an effective identification of patients with an atypical meningioma who have an increased risk of tumor progression.


The molecular basis of Src kinase specificity during vertebrate mesoderm formation.
Members of the Src family of non-receptor tyrosine kinases play a critical role in mesoderm formation in the frog, Xenopus laevis, acting as required mediators downstream of the fibroblast growth factor receptor. At least four members of this gene family, Src, Fyn, Yes, and Laloo, are expressed during early embryonic development. Ectopic expression of Laloo and Fyn, but not Src, induce mesoderm in ectodermal explants, indicating that these factors are non-redundant during early vertebrate development. Here we investigate the basis for the differential activity of the Src and Laloo kinases during mesoderm formation. We demonstrate that although both Src and Laloo physically interact with the substrate protein SNT-1/FRS2alpha only Laloo phosphorylates SNT-1, an event previously shown to be required for the activity of the latter and for mesoderm induction in vivo. We show that Src is enzymatically capable of stimulating mesoderm formation, as an activated Src construct both phosphorylates SNT-1 and induces mesoderm in explant cultures. However, a chimeric Laloo construct containing a Src C-terminal tail is inactive, suggesting that the early embryo contains a specific Laloo-activating, or Src-inactivating, factor. Finally, through further chimeric analysis, we provide evidence to suggest that differences in Laloo and Src activity are also mediated by the SH2, SH3, and kinase domains of these molecules.


Rapid investigation of sedimentation phenomena by vibrational force field.
A new method for the rapid investigation of sedimentation phenomena of fine particles is developed by using the force due to a vibrational acceleration. The small displacement of the particle with respect to the wall of the container, which is produced by the vibration, is measured by the interference between the light scattered by the particle and that of the cell wall. The interference is detected as a beat note in the scattered-light intensity, and displayed as a time-autocorrelation of the photocurrent, the analysis of which gives the sedimentation coefficient and the dispersion.


[Isolation of glutamylendopeptidase precursor from B. licheniformis and its processing in vitro].
A secretory system based on L-form cells of Proteus mirabilis was developed for production of native Bacillus licheniformis glutamylendopeptidase precursor never formerly available. The produced precursor was stable per se under physiological conditions and in presence of trypsin and glutamylendopeptidase from B. intermedius. Complete conversion of the precursor to the mature glutamylendopeptidase was performed by bacillar metalloproteases and subtilisin. The artificially processed glutamylendopeptidase was purified by affinity chromatography on bacitracin-sepharose. Native tertiary structure in the purified glutamylendopeptidase was confirmed by demonstrating its activity towards a specific chromogenous peptide substrate.


Hormonal and splanchnic hemodynamic alterations following hepatic resection.
Reported hemodynamic changes after partial hepatectomy (PH) include elevations in portal blood flow and pressure (Ppv). The etiology of these changes is unknown. We studied degree of portosystemic shunt (PSS), splanchnic artery blood flow and resistance (Qspl, Rspl) as well as prostacyclin (PGI2), glucagon, and insulin response in rats undergoing 75% hepatectomy. The results showed that following an immediate threefold rise in portal PGI2, a hemodynamically significant PSS developed at 48 hr. The PGI2 changes paralleled the increase in portal flow (Qpv), pressure (Ppv), PSS and the decrease in Rspl. Glucagon levels also rose immediately postresection, but fell to normal prior to resolution of both PSS and hyperemia. There was no significant change in insulin or glucose levels after resection. This implies a relationship between PSS and the release of a prostanoid effecting Qpv, Qspl, and Rspl, which relates to, and possibly mediates, the hemodynamic changes following liver resection. We conclude that PH is a model of acute PHT, and that the altered splanchnic hemodynamic could relate to hepatic regeneration.


Optimizing post-polypectomy surveillance: A practical guide for the endoscopist.
Several gastrointestinal societies strongly recommend colonoscopy surveillance after endoscopic and surgical resection of colorectal neoplasms. Common denominators to these recommendations include: high-quality baseline colonoscopy before inclusion in a surveillance program; risk stratification based on clinicopathological profiles to guide surveillance intervals; and endoscopist responsibility for providing surveillance advice. Considerable variability also exists between guidelines (i.e. regarding risk classification and surveillance intervals). In this review, we examine key factors for quality of post-polypectomy surveillance practice, in particular bowel preparation, endoscopic findings at baseline examination and adherence to surveillance recommendations. Frequently asked questions by the practising endoscopist are addressed.


Operative treatment of the difficult stage 2 adult acquired flatfoot deformity.
In the flexible pes planovalgus deformity of stage 2 posterior tibial tendon dysfunction, osteotomies appear to have a significant role in operative management by restoring more normal biomechanics, allowing tendon transfers to function successfully. The options when considering osteotomies for stage 2 disease include lateral column lengthening, medial displacement calcaneal osteotomy, and combined double osteotomy technique. The tight Achilles tendon should be lengthened as well. Lateral column lengthening has been used extensively for treatment of flexible flatfeet. It has been shown clinically and radiographically to address all 3 components of the pes planovalgus deformity present in stage 2 posterior tibial tendon dysfunction. Lateral column lengthening is used in combination with a medial soft tissue rebalancing procedure. The mechanism of action is still speculative but clearly is not owing to tensioning of the plantar fascia as previously thought. Despite the excellent correction of foot posture obtained by use of lateral column lengthening for adult acquired flatfoot, many clinicians have reservations about its use because of reported secondary increases in the calcaneocuboid joint pressures. This increase in pressure has been shown to occur experimentally, increasing the potential risk of calcaneocuboid joint arthrosis. This experimental evidence is supported by Phillips' study of the original Evans procedure, which resulted in a 65% incidence of calcaneocuboid joint arthrosis at 13-year follow-up. Mosier-LaClair et al reported a 14% incidence of calcaneocuboid joint arthritis at 5-year follow-up after double osteotomy for stage 2 posterior tibial tendon dysfunction. This incidence has not been proved true in the remainder of the literature surrounding this procedure and its use for flexible flatfoot. To address the concern regarding potential calcaneocuboid arthrosis secondary to lateral column lengthening, calcaneocuboid joint distraction arthrodesis has been explored as an alternative technique. The results show good initial correction, but the follow-up is extremely limited, and one study reported loss of correction over time. Longer follow-up is needed to determine whether or not this technique would provide the lasting correction seen with the Evans procedure. Calcaneocuboid joint lengthening arthrodesis does result in some limitation of adjacent hindfoot motion. Although this limitation is significantly less compared with talonavicular and subtalar joint fusion, this procedure may result in increased local pressures and arthrosis of the midfoot or hindfoot. For the above-mentioned reasons, longer follow-up studies are needed to determine whether calcaneocuboid joint distraction arthrodesis would prove to be a reliable and safe alternative for lateral column lengthening in the treatment of adult acquired flatfoot. Medial displacement calcaneal osteotomy has been used for correction of the pes planovalgus foot in posterior tibial tendon dysfunction. It has been used extensively for the surgical treatment of flexible flatfoot throughout the literature. Medial displacement osteotomy, in combination with flexor digitorum longus tendon transfer, can address all 3 components of adult acquired flatfoot. It does not recreate the medial longitudinal arch in all patients, however. Although the mechanism of action of medial displacement calcaneal osteotomy is unknown, it has been proved that it is not through the tightening of the plantar fascia in a windlass effect as previously thought. In contrast to lateral column lengthening, however, medial displacement calcaneal osteotomy does address the deforming valgus force of the Achilles tendon. Functionally transferring the insertion of the Achilles tendon medially removes a constant valgus-deforming force. The osteotomy can then act as a double tendon transfer with the flexor digitorum longus tendon to aid in foot inversion. For stage 2 posterior tibial tendon insufficiency, the authors favor the combination double osteotomy technique with a flexor digitorum longus tendon-to-medial cuneiform tendon transfer, débridement or removal of the posterior tibial tendon, and percutaneous heel cord lengthening. Early results were positive at 1.5 years after surgery with respect to maintenance of correction and functional improvement with no evidence of calcaneocuboid arthrosis. More recently, the intermediate 5-year follow-up has been assessed for this combination of procedures, and similar results were found. There was a high rate of patient satisfaction and functional improvement, and surgical correction of the flatfoot deformity was maintained and compared favorably with the contralateral normal foot. Although the intermediate follow-up found a 14% incidence of calcaneocuboid arthrosis, 50% of these patients had preoperative evidence of calcaneocuboid joint arthritis. (ABSTRACT TRUNCATED)


Protein analysis of Theileria sergenti/buffeli/orientalis piroplasms by two-dimensional polyacrylamide gel electrophoresis.
Proteins of the piroplasms of Theileria sergenti, T. buffeli and T. orientalis were analysed by two-dimensional polyacrylamide gel electrophoresis. Protein spot patterns of T. buffeli and T. orientalis were identical except for a few minor proteins, whereas spot patterns of two T. sergenti stocks were differentiated from those of T. buffeli and T. orientalis by a characteristic set of proteins including a major protein of molecular weight 33-34 kDa. This result indicates that Japanese T. sergenti can be phenotypically distinguishable from European and Australia Theileria species; T. orientalis and T. buffeli.


New noncontact devices for measuring small microdisplacements.
The visual method suitable for longitudinal optical settings, based on the observation of equal modulations produced by two periodic tests when depth is shifted, is recalled and shown to provide sensitivity 100 times greater than conventional methods. A photoelectric adaptation of this method is described, as well as two devices that can be used to maintain focus within the same sensitivity. The first is designed to detect the difference of modulations of the image of a line or point source as measured in two planes situated on both sides of the source. The second is designed to detect the difference of encircled energies of the images of the same source as measured in two identical planes. Results from both devices are compared.


DRD4 related to infant attention and information processing: a developmental link to ADHD?
The dopamine D4 receptor (DRD4) exon III polymorphism has generated interest because of its association with attention deficit hyperactivity disorder (ADHD), with an increased frequency of the seven-repeat allele being reported in children with ADHD. Deficits in sustained attention and information processing characterize ADHD, and individual differences in these functions are apparent from infancy. We found that in a structured play situation and on an information-processing task, 1-year-old infants with the 7-DRD4 allele showed less sustained attention and novelty preference than do infants without the 7-DRD4 allele. There was also a significant interaction between DRD4 and the serotonin transporter promoter (5-HTTLPR) gene on a measure of sustained attention. Our results provide evidence for a possible developmental link between DRD4 and ADHD via early sustained attention and information processing. It also points to the importance of considering the influence of more than one gene in studies of behavior.


Hyphessobrycon petricolus, a new species of tetra (Characiformes: Characidae) from the rio Madeira basin, Mato Grosso, Brazil.
A new species of Hyphessobrycon is described from the rio Roosevelt, rio Madeira basin, Mato Grosso State, Brazil. Hyphessobrycon petricolus sp. n. can be distinguished from its congeners by the unique combination of the following features: a well-defined, relatively narrow dark midlateral stripe on body extending from immediately behind posterior margin of opercle to the middle caudal-fin rays, relatively conspicuous humeral blotch, and 16-20 branched anal-fin rays. Comments on the remaining Hyphessobrycon species presenting a conspicuous dark midlateral stripe are presented.


Induction of glutathione s-transferase isozymes in sorghum by herbicide antidotes.
Certain chemicals referred to as herbicide antidotes protect sorghum from injury by chloroacetanilide herbicides such as metolachlor. The effect of herbicide antidotes on the glutathione S-transferase isozyme complement of etiolated sorghum (Sorghum bicolor [L.] Moench) shoots was examined. Elution profiles of glutathione S-transferase isozymes from untreated and antidote-treated seedlings were generated by fast protein liquid chromatography utilizing an anion exchange (Mono Q) column. In untreated seedlings, there were two glutathione S-transferase isozymes, a major isozyme which exhibited activity toward 1-chloro-2,4-dinitrobenzene and a minor isozyme which exhibited activity toward metolachlor. Treating sorghum seedlings with various antidotes (flurazole, oxabetrinil, CGA-133205, naphthalic anhydride, dichlormid) resulted in the appearance of four to five additional glutathione S-transferase isozymes (de-pending on the particular antidote) which exhibited activity toward metolachlor as a substrate and little or no activity with 1-chloro-2,4-dinitrobenzene. Treating etiolated sorghum shoots with metolachlor was also found to induce at least four isozymes which exhibited activity toward the herbicide. An increase in glutathione S-transferase activity, measured with metolachlor as substrate, was detected within 4 h after treatment with 30 micromolar oxabetrinil, but 36 hours were required for maximum expression of activity. Addition of either the transcription inhibitor cordycepin or the translation inhibitor cycloheximide inhibited the appearance of glutathione S-transferase activity measured with metolachlor as substrate. The results are consistent with the hypothesis that antidotes confer protection against metolachlor injury in sorghum by inducing the de novo synthesis of glutathione S-transferase isozymes which catalyze the detoxification of the herbicide.


Biofilm formation and composition on different implant materials in vivo.
Biofilm formation was evaluated on the following titanium and zirconia implants in vivo: machined titanium (Ti-m), modified titanium (TiUnite), modified zirconia (ZiUnite), machined alumina-toughened zirconia (ATZ-m), sandblasted alumina-toughened zirconia (ATZ-s), and machined zirconia (TZP-A-m). Bovine enamel slabs were used as controls. Surface morphologies were examined by atomic force (AFM) and scanning electron microscopy (SEM). The surface wettability was also determined. Twelve healthy volunteers wore a splint system with the tested materials. After 3 and 5 days the materials were examined by fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy (CLSM). The levels of Streptococcus spp., Veillonella spp., Fusobacteriaum nucleatum, and Actinomyces naeslundii were quantitatively determined. The biofilm thickness was found to be between 19.78 and 36.73 μm after 3 days and between 26.11 and 32.43 μm after 5 days. With the exception of Ti-m the biofilm thickness after 3 days was correlated with surface roughness. In addition to Streptococcus spp. as the main component of the biofilm (11.23-25.30%), F. nucleatum, A. naeslundii, and Veillonella spp. were also detected. No significant differences in biofilm composition on the implant surfaces could be observed. In total, the influence of roughness and material on biofilm formation was compensated by biofilm maturation.


Aggregation-Induced-Emission-Active Macrocycle Exhibiting Analogous Triply and Singly Twisted Möbius Topologies.
Molecules with Möbius topology have drawn increasing attention from scientists in a variety of fields, such as organic chemistry, inorganic chemistry, and material science. However, synthetic difficulties and the lack of functionality impede their fundamental understanding and practical applications. Here, we report the facile synthesis of an aggregation-induced-emission (AIE)-active macrocycle (TPE-ET) and investigate its analogous triply and singly twisted Möbius topologies. Because of the twisted and flexible nature of the tetraphenylethene units, the macrocycle adjusts its conformations so as to accommodate different guest molecules in its crystals. Moreover, theoretical studies including topological and electronic calculations reveal the energetically favorable interconversion process between triply and singly twisted topologies.


Serine hydroxymethyltransferase: origin of substrate specificity.
All forms of serine hydroxymethyltransferase, for which a primary structure is known, have five threonine residues near the active-site lysyl residue (K229) that forms the internal aldimine with pyridoxal phosphate. For Escherichia coli serine hydroxymethyltransferase each of these threonine residues has been changed to an alanine residue. The resulting five mutant enzymes were purified and characterized with respect to kinetic and spectral properties. The mutant enzymes T224A and T227A showed no significant changes in kinetic and spectral properties compared to the wild-type enzyme. The T225A and T230A enzymes exhibited differences in Km and kcat values but exhibited the same spectral properties as the wild-type enzyme. The four threonine residues at positions 224, 225, 227, and 230 do not play a critical role in the mechanism of the enzyme. The T226A enzyme had nearly normal affinity for substrates and coenzymes but had only 3% of the catalytic activity of the wild-type enzyme. The spectrum of the T226A enzyme in the presence of amino acid substrates showed a large absorption maximum at 343 nm with only a small absorption band at 425 nm, unlike the wild-type enzyme whose enzyme-substrate complexes absorb at 425 nm. Rapid reaction studies showed that when amino acid substrates and substrate analogues were added to the T226A enzyme, the internal aldimine absorbing at 422 nm was rapidly converted to a complex absorbing at 343 nm in a second-order process. This was followed by a very slow first-order formation of a complex absorbing at 425 nm.(ABSTRACT TRUNCATED AT 250 WORDS)


Lactic acid from vaginal microbiota enhances cervicovaginal epithelial barrier integrity by promoting tight junction protein expression.
Women with a cervicovaginal microbiota dominated by Lactobacillus spp. are at reduced risk of acquiring sexually transmitted infections including HIV, but the biological mechanisms involved remain poorly defined. Here, we performed metaproteomics on vaginal swab samples from young South African women (n = 113) and transcriptomics analysis of cervicovaginal epithelial cell cultures to examine the ability of lactic acid, a metabolite produced by cervicovaginal lactobacilli, to modulate genital epithelial barrier function. Compared to women with Lactobacillus-depleted microbiota, women dominated by vaginal lactobacilli exhibit higher abundance of bacterial lactate dehydrogenase, a key enzyme responsible for lactic acid production, which is independently associated with an increased abundance of epithelial barrier proteins. Physiological concentrations of lactic acid enhance epithelial cell culture barrier integrity and increase intercellular junctional molecule expression. These findings reveal a novel ability of vaginal lactic acid to enhance genital epithelial barrier integrity that may help prevent invasion by sexually transmitted pathogens. Video abstract.


Label-free separation of nanoscale particles by an ultrahigh gradient magnetic field in a microfluidic device.
The need for fast and accurate analysis of low-concentration species is ubiquitous nowadays. The separation and purification techniques restrict the highly sensitive detection of low-abundance nanoparticles. On the other hand, the commonly used separation techniques of labeling procedures limit their implementation in various applications. We report a microfluidic system with ultrahigh magnetic field for the label-free separation of nanoscale particles. Using high-permeability alloys and on-chip integrated magnetic micro-pole arrays, the external strong magnetic field can be conducted into the microfluidic device to form a magnetic field of high intensity and gradient, therefore separating particles of nanometer size with high efficiency. An ultrahigh gradient magnetic field greater than 105 T m-1 can be generated in the separation channel. Moreover, a negative magnetophoretic technique to separate nanoparticles is established in this device. Then, the label-free separation of nanoparticles is achieved in this microfluidic system perfused by a ferrofluid with an extremely low concentration (0.01%). A mixture of 0.2 μm and 1 μm particles is used to verify the performance of the device, where the recovery rate of 0.2 μm particles is 88.79%, and the purity reaches 94.72%. Experimental results show that the device can efficiently separate nanoscale particles with ultrahigh resolution, and in future, it may develop into a versatile and robust tool for the separation and purification of the biological samples of nanometer size.


Bis(oxazolinyl)phenyl transition-metal complexes: asymmetric catalysis and some reactions of the metals.
Several transition-metal complexes that bind the bis(oxazolinyl)phenyl moiety as a tridentate ligand have been prepared to showcase their highly potent activities for asymmetric catalysis in conjugate reductions, reductive aldol reactions, direct aldol reactions and hydrogenation reactions. Some reactions of the metals were also examined.


Do human atherosclerotic lesions contain nitrotyrosine?
Nitrotyrosine has been widely used as a marker of peroxynitrite formation in normal and diseased tissues. However, studies of normal human aortic intima and atherosclerotic lesions at various stages of development failed to reveal its presence except in a very few specimens of both normal and diseased tissues. The techniques used to detect nitrotyrosine-HPLC with photodiode array detection and Western blotting- were able to identify nitrotyrosine after chemical nitration. Hence peroxynitrite may not be as important in the initiation of atherosclerosis as has commonly been proposed.


The effect of probenecid on serum amoxycillin concentrations up to 18 hours after a single 3 g oral dose of amoxycillin: possible implications for preventing endocarditis.
Serum concentrations of amoxycillin were significantly higher with probenecid than without probenecid for up to 18 h after administration of a single 3 g oral dose of amoxycillin. At 12 to 16 h after this dose the mean serum amoxycillin concentrations exceeded the expected minimum bactericidal concentrations of amoxycillin for viridans streptococci when probenecid was given together with amoxycillin. The concurrent oral administration of probenecid with amoxycillin is discussed for the prophylaxis of endocarditis in susceptible patients who require dental procedures under general anaesthesia.


Protective effect of 2-deoxy-D-glucose on the brain tissue in rat cerebral ischemia-reperfusion models by inhibiting Caspase-apoptotic pathway.
We observed the effect of 2-deoxy-D-glucose (2-DG) on the brain tissue in rat cerebral ischemia-reperfusion (I/R) and explored its mechanism. After observing the effect of 2-DG on endoplasmic reticulum stress (ERS), rats were randomly divided into sham-operation group, I/R group and I/R+2-DG group (each group with 60 rats). I/R models were prepared by middle cerebral artery occlusion. In I/R+2-DG group, each rat was given intraperitoneal 2-DG of 100 mg/kg once a day for 7 days before brain ischemia. According to different time points (3h, 6h, 12h, 24h and 48h) after I/R, each group was divided into 5 subgroups (each subgroup with 12 rats). Nerve cell apoptosis, and the expressions of mRNA and protein of glucose regulated protein 78 (GRP78), cleaved-caspase-9 and cleaved-caspase-3 were determined with TUNEL, Western blotting and RT-PCR, respectively, in rat cerebral hippocampal CA1 area at each time point. TUNEL-positive cells were significantly less in I/R+2-DG group than in I/R group at each time point (all P<0.01). In I/R and I/R+2-DG groups, the expressions of mRNA and protein of GRP78 reached the maximum 12 h after I/R, and cleaved-caspase-9 and cleaved-caspase-3 reached the maximum 24 h after I/R. Compared with sham-operation group, the expressions of mRNA and protein of GRP78, cleaved-caspase-9 and cleaved-caspase-3 were all significantly increased (all P<0.01) in I/R and I/R+2-DG groups. However, the expressions of mRNA and protein of GRP78 were significantly higher in I/R+2-DG group than in I/R group (all P<0.05), but the expressions of mRNA and protein of cleaved-caspase-9 and cleaved-caspase-3 were all significantly lower in I/R+2-DG group than in I/R group (all P<0.05). We conclude that 2-DG has a neuroprotective effect on the brain tissue in rat cerebral ischemia-reperfusion models. The mechanism may be that 2-DG starts ERS followed by up-regulation of mRNA and protein of GRP78 and down-regulation of mRNA and protein of cleaved-caspase-9 and cleaved-caspase-3, which blocks the apoptotic pathway.


Prevalence of otitis media with effusion in multicultural schools in Hong Kong.
The prevalence of otitis media with effusion (OME) in Asia has only been studied in a limited fashion. This preliminary study forms part of a larger study aiming to establish the prevalence of OME in Hong Kong. One hundred and seventy-seven children (from multicultural schools) between the ages of five and 6.03 years were screened for OME otoscopy and tympanometry. Nine positive screens (5.1 per cent) were obtained for OME. Within this mixed ethnic group, Chinese children had a significantly lower point prevalence (1.3 per cent) than Caucasian children (9.5 per cent) (p < 0.05). Although the point prevalence from this mixed ethnic group of children was significantly higher (p < 0.05) than that of local Chinese school children (1.95 per cent) by the same group of investigators, the point prevalence in the ethnic Chinese children was comparable. The reason for the lower prevalence of OME in the Chinese population needs further research.


On the preservation of vessel bifurcations during flow-mediated angiogenic remodelling.
During developmental angiogenesis, endothelial cells respond to shear stress by migrating and remodelling the initially hyperbranched plexus, removing certain vessels whilst maintaining others. In this study, we argue that the key regulator of vessel preservation is cell decision behaviour at bifurcations. At flow-convergent bifurcations where migration paths diverge, cells must finely tune migration along both possible paths if the bifurcation is to persist. Experiments have demonstrated that disrupting the cells' ability to sense shear or the junction forces transmitted between cells impacts the preservation of bifurcations during the remodelling process. However, how these migratory cues integrate during cell decision making remains poorly understood. Therefore, we present the first agent-based model of endothelial cell flow-mediated migration suitable for interrogating the mechanisms behind bifurcation stability. The model simulates flow in a bifurcated vessel network composed of agents representing endothelial cells arranged into a lumen which migrate against flow. Upon approaching a bifurcation where more than one migration path exists, agents refer to a stochastic bifurcation rule which models the decision cells make as a combination of flow-based and collective-based migratory cues. With this rule, cells favour branches with relatively larger shear stress or cell number. We found that cells must integrate both cues nearly equally to maximise bifurcation stability. In simulations with stable bifurcations, we found competitive oscillations between flow and collective cues, and simulations that lost the bifurcation were unable to maintain these oscillations. The competition between these two cues is haemodynamic in origin, and demonstrates that a natural defence against bifurcation loss during remodelling exists: as vessel lumens narrow due to cell efflux, resistance to flow and shear stress increases, attracting new cells to enter and rescue the vessel from regression. Our work provides theoretical insight into the role of junction force transmission has in stabilising vasculature during remodelling and as an emergent mechanism to avoid functional shunting.


Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies with hepatitis B and hepatitis C infection: Review.
Viruses are common and are involved in the etiology of idiopathic rheumatological diseases. Hepatitis B virus (HBV), a member of the family Hepadnaviridae and hepatitis C virus (HCV), play an important role in the undetermined etiology of arthritis. The clinical manifestations of hepatitis B and C show similarities with various diseases, such as rheumatic diseases. Anti-cyclic citrullinated peptide (anti-CCP) is a specific serological marker for rheumatoid arthritis. The aim of this study was to analyze anti-CCP and rheumatoid factor (RF) levels in patients with a hepatitis B and C infection. Forty-four patients with hepatitis B, 43 patients with hepatitis C, 25 patients with rheumatoid arthritis, and 46 healthy control serums and their RF and anti-CCP levels were compared. RF was measured by the nephelometer, which detects IgM-RF. Anti-CCP was measured using enzymelinked immunosorbent assay (ELISA) that is included in the second-generation anti-CCP antibody assays (anti-CCP2). The anti-CCP positivity levels were 20.5%, 32.5%, 72.4% and 10.9% for HBV, HCV and RA groups and healthy control group, respectively. When the groups were compared based on their RF positivity and anti-CCP positivity while the values for HBV and HCV group and healthy control group were the same, in RA group there is a significant difference to the rest of the groups (p < 0.01). Anti-CCP may be positive for HBV and HCV as well, but it is a sensitive and specific immunological marker for RA diagnosis, especially in high-titres.


[Long-term results of the surgical treatment of spheno-orbital osteomeningioma].
The authors report a series of 21 cases of spheno-orbital "en plaque" meningiomas operated on between 1981 and 1993. All patients underwent surgery via fronto-temporal approach with orbito-zygomatic removal, followed by bone reconstruction. A complete tumor resection was performed in 15 cases. In the remaining patients, tumor resection remained subtotal, as the cavernous sinus was involved. Histological examination disclosed a low grade meningioma in 17 cases, high grade meningioma in the other patients. Radiation therapy was performed in 5 patients, when the tumoral resection was incomplete or for high grade meningiomas. The mean follow up was 7 years. One patient died in the post-operative course. Transient ophthalmoparesis occurred in 9 cases, 2 patients had pre-operative oculomotor palsy related to tumoral extension in the cavernous sinus and remained unchanged. Visual acuity remained unchanged after surgery in all patients who presented with normal visual acuity. It was unchanged or improved in 63% of patients who presented with moderate visual impairment. Despite the extent of the bone resection, the cosmetic results were good or excellent in 75% of patients, fair in 17%, and bad in 8%. Recurrence of the tumor occurred in 3 patients, with high-grade meningiomas (2 cases) or after subtotal removal of a low-grade meningioma (1 case). Orbito-fronto-temporal approach is necessary to complete the resection of the tumor extended in the orbit, the orbital fissures or the optic canal. Early operation allows a complete tumor resection before the tumor extends to the cavernous sinus.


Analysis of skeletal muscle metabolome: evaluation of extraction methods for targeted metabolite quantification using liquid chromatography tandem mass spectrometry.
Functional metabolomics of skeletal muscle involves the simultaneous identification and quantification of a large number of metabolites. For this purpose, the extraction of metabolites from animal tissues is a crucial technical step that needs to be optimized. In this work, five extraction methods for skeletal muscle metabolome analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) were tested. Bird skeletal muscles sampled postmortem and quenched in liquid nitrogen were used. Three replicates of the same sample were extracted using the following solvent systems of varying polarity: boiling water (BW, +100 degrees C), cold pure methanol (CPM, -80 degrees C), methanol/chloroform/water (MCW, -20 degrees C), boiling ethanol (BE, +80 degrees C), and perchloric acid (PCA, -20 degrees C). Three injections by extraction were performed. The BW extraction showed the highest recovery of metabolites with the lowest variability (<10%) except for creatine-phosphate (creatine-P). Considering yield (area of the peaks), reproducibility, and ease, the current experiment drew a scale for the muscle metabolome extraction starting from the best to the least convenient: BW>MCW>CPM>PCABE. In addition, the semiquantification of metabolites in two muscles showing different metabolic and contractile properties was carried out after BW extraction and showed expected differences in metabolite contents, thereby validating the technique for biological investigations. In conclusion, the BW extraction is recommended for analysis of skeletal muscle metabolome except for creatine-P, which was poorly recovered with this technique.


Enterococcus faecalis V583 cell membrane protein expression to alkaline stress.
Enterococcus faecalis is able to adapt to alkaline conditions and is commonly recovered from teeth in which endodontic treatment has failed. The role that E. faecalis membrane proteins play in survival strategies to extreme alkaline conditions is unclear. We grew E. faecalis V583 in a chemostat at pH 8 and 11 at one-tenth the organism's relative maximum growth rate. Following membrane shaving, isotope-coding protein labels were added at the peptide level to samples and then combined. The relative proportion of membrane proteins were identified using LC-ESI mass spectrometry and MaxQuant analysis. Ratios of membrane proteins were log2 transformed, with proteins deviating by more than 1 SD of the mean considered to be up- or down-regulated. A total of six proteins were up-regulated in pH 11 including: EF0669 (polysaccharide biosynthesis family); EF1927 (glycerol uptake facilitator), and EF0114 (glycosyl hydrolase). A total of five proteins were down-regulated including: EF0108 (C4-dicarboxylate transporter); EF1838 (PTS system IIC component); EF0456 (PTS system IID component); and EF0022 (PTS mannose-specific IID component). In extreme alkaline conditions, the membrane proteins of E. faecalis seem to be involved in a shift of carbohydrate metabolism from the PTS system to glycerol, which supports the formation of a protective capsule protecting the cell.


[A case of acute monocytic leukemia cutis treated with total skin electron beam irradiation].
A 35-year-old man with acute monocytic leukemia (AMoL) cutis was treated with total skin electron beam irradiation (TSEBI), because the widespread skin infiltration of AMoL appeared after induction chemotherapy. A skin nodule was authenticated as leukemic cell by biopsy. The patient was irradiated 4 times a week with 200 cGy per fraction to a total dose of 1200 cGy, using 6 MeV electrons from 8 directions. The therapy was accomplished separately on the upper and lower halves of the body. Focus-skin distance was 310 cm. An acrylic plate applicator 1 cm in thickness was used. The dimensions were 90 x 90 cm inside length and 90 cm in height. After completion of radiotherapy, the nodular lesions of the skin nearly disappeared. Although the patient survived only 3.5 months after beginning of radiotherapy due to systemic relapse, recurrence of the skin nodule was not seen. In this case TSEBI was therefore a useful treatment for skin infiltration of AMoL.


In vivo electroporetic transfer of bcl-2 antisense oligonucleotide inhibits the development of hepatocellular carcinoma in rats.
To investigate the potential use of a bcl-2 antisense oligonucleotide for therapy against hepatocellular carcinoma, we examined the effects of the electroporetic transfer of a bcl-2 antisense oligonucleotide on rat hepatocarcinogenesis induced by N-nitrosomorpholine (NNM). Sprague-Dawley rats were given water containing 175 mg/l NNM for 8 weeks and received intraperitoneal injections of a bcl-2 antisense phosphorothioate oligonucleotide, a sense oligonucleotide or a scrambled sequence oligonucleotide encapsulated in empty liposomes, at a dose of 150 microg oligonucleotide/kg body weight, every 4 weeks. One hour after injection, in vivo electroporation was performed on the liver to achieve selective transfer of the oligonucleotides. By week 16, the rats that had received the bcl-2 antisense oligonucleotide had significantly fewer and smaller precancerous liver lesions positive for glutathione-S-transferase (placental type), and a significantly lower incidence of hepatocellular carcinoma in the electroporation zone than rats that had received the sense or the scrambled oligonucleotides. Moreover, the bcl-2 antisense oligonucleotide significantly increased the apoptotic indices in foci, neoplastic nodules and in hepatocellular carcinomas. The expression of bcl-2 mRNA also decreased, and 3'-fragments of bcl-2mRNA produced by cleavage at the antisense target site were detected in rat liver. Mean cellular fluorescence in the liver increased with higher doses of fluorescein-isothiocyanate-labeled antisense or sense oligonucleotides. Our results show that the electroporetic transfer of bcl-2 antisense oligonucleotide can inhibit rat hepatocarcinogenesis.


Kinetin Enhanced 1-Aminocyclopropane-1-Carboxylic Acid Utilization during Alleviation of High Temperatures Stress in Lettuce Seeds.
The thermoinhibition at 35 and 32 degrees C of pregermination ethylene production and germination in lettuce (Lactuca sativa L. cv Mesa 659) seeds was synergistically or additively alleviated by 0.05 millimolar kinetin (KIN) and 10 millimolar 1-aminocyclopropane-1-carboxylic acid (ACC). The synergistic effect of KIN + ACC on ethylene production and germination at 35 degrees C was inhibited by Co(2+) (44-46%) but not by aminoethoxyvinyl glycine (AVG). The uptake of ACC by the seed was not influenced by KIN. Upon slitting of the seed coats (composed of pericarp, testa and endosperm), following the uptake of chemicals, ACC was readily converted into ethylene at all temperatures, and the synergistic effects of KIN + ACC at 35 degrees C were lost. At 35 degrees C, KIN acted synergistically with ACC or ethephon (ETH) in alleviating the osmotic restraint. At 25 degrees C, ETH was more active than KIN or KIN + ACC in overcoming the osmotic restraint. Thus, the integrity of the seed coats, the KIN-enhanced ACC utilization, and an interaction of KIN with the ethylene produced may be the basis for the synergistic or additive effects of KIN + ACC at high temperature.


Spatial sampling and filtering of EEG with spline laplacians to estimate cortical potentials.
The electroencephalogram (EEG) is recorded by sensors physically separated from the cortex by resistive skull tissue that smooths the potential field recorded at the scalp. This smoothing acts as a low-pass spatial filter that determines the spatial bandwidth, and thus the required spatial sampling density, of the scalp EEG. Although it is better appreciated in the time domain, the Nyquist frequency for adequate discrete sampling is evident in the spatial domain as well. A mathematical model of the low-pass spatial filtering of scalp potentials is developed, using a four concentric spheres (brain, CSF, skull, and scalp) model of the head and plausible estimates of the conductivity of each tissue layer. The surface Laplacian estimate of radial skull current density or cortical surface potential counteracts the low-pass filtering of scalp potentials by shifting the spatial spectrum of the EEG, producing a band-passed spatial signal that emphasizes local current sources. Simulations with the four spheres model and dense sensor arrays demonstrate that progressively more detail about cortical potential distribution is obtained as sampling is increased beyond 128 channels.


Preoperative inflammatory markers as prognostic predictors after hepatocellular carcinoma resection: data from a western referral center.
Recent studies from eastern centers have demonstrate an association between inflammatory response and long-term outcomes after hepatocellular carcinoma (HCC) resection. However, the prognostic impact of inflammatory markers in western patients, with distinct tumor and epidemiologic features, is still unknown. To evaluate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as well as their impact according to tumor size (< 5 cm, 5-10 cm, > 10 cm) in patients undergoing HCC resection with curative intent. Optimal cut-off values for NLR, PLR, and MLR were determined by plotting the receiver operator curves. Overall survival (OS) and disease-free survival (DFS) curves were calculated using the Kaplan-Meier method and compared using the log-rank test. The Cox method was used to identify independent predictors of OS and DFS. In total, 161 consecutive adult patients were included. A high NLR (> 1.715) was associated with worse OS (P = 0.018). High NLR (> 2.475; P = 0.047) and PLR (> 100.25; P = 0.028) were predictors of short DFS. In HCC < 5 cm, MLR (> 1.715) was associated with worse OS (P = 0.047). In the multivariate analysis, high PLR was an independent predictor of worse DFS [hazard ratio (HR) 3.029; 95%CI 1.499-6.121; P = 0.002]. Inflammatory markers are useful tools to predict long-term outcomes after liver resection in western patients, high NLR was able to stratify subgroups of patients with short OS and DFS, an increased PLR was an independent predictor of short DFS, while high MLR was associated with short OS in patients with early HCC.


Relationship Between Implementation of Collaborative Strategic Reading and Student Outcomes for Adolescents With Disabilities.
This study examines the interaction between the fidelity of implementation of a set of research-based strategies-Collaborative Strategic Reading (CSR)-and outcomes for students with mild to moderate disabilities using data from two nonoverlapping studies in middle school language arts and reading classrooms (Study 1) and middle school social studies and science classrooms (Study 2). The authors use a definition of fidelity that includes both the amount of CSR instruction delivered by teachers and the quality of implementation. Although there were no main effects for quality or amount of CSR instruction, in both studies there was an interaction effect between quality of implementation and special education status. The study used a within-groups design and multilevel analyses, and the results demonstrate that higher quality CSR instruction was associated with higher reading outcomes for students with disabilities. This finding was consistent across Study 1 and Study 2. Implications for practice and future research are discussed.


Herpes simplex Virus Esophagitis in an Immunocompetent Patient with Ebstein-Barr Virus Infection.
Epstein-Barr virus infectious mononucleosis can cause transient immune deficiency which may predispose to reactivation of latent herpes simplex virus (HSV) infection in the immunocompetent host. We report the case of a 15-year-old male who presented with severe odynophagia and herpes labialis during the course of Epstein-Barr virus infectious mononucleosis that had been diagnosed ten days before. Esophagoscopy revealed extensive ulcerations with distinct borders and whitish exudates at the mid and distal esophagus. Polymerase chain reaction detected HSV-1 DNA in the biopsy specimens. The patient was treated with intravenous acyclovir. The symptoms resolved rapidly within 3 days, in accordance with improved endoscopic findings.


Prediction of Protein-ligand Interaction Based on Sequence Similarity and Ligand Structural Features.
Computationally predicting the interaction of proteins and ligands presents three main directions: the search of new target proteins for ligands, the search of new ligands for targets, and predicting the interaction of new proteins and new ligands. We proposed an approach providing the fuzzy classification of protein sequences based on the ligand structural features to analyze the latter most complicated case. We tested our approach on five protein groups, which represented promised targets for drug-like ligands and differed in functional peculiarities. The training sets were built with the original procedure overcoming the data ambiguity. Our study showed the effective prediction of new targets for ligands with an average accuracy of 0.96. The prediction of new ligands for targets displayed the average accuracy 0.95; accuracy estimates were close to our previous results, comparable in accuracy to those of other methods or exceeded them. Using the fuzzy coefficients reflecting the target-to-ligand specificity, we provided predicting interactions for new proteins and new ligands; the obtained accuracy values from 0.89 to 0.99 were acceptable for such a sophisticated task. The protein kinase family case demonstrated the ability to account for subtle features of proteins and ligands required for the specificity of protein-ligand interaction.


[The general lipid and lipid peroxidation byproduct content in the erythrocyte membrane among patients with gun shot pulmonary wound].
In the injured persons with gun shot wounds of thorax the lowering of the common lipids lever, high contents of dienic ketones, dienic conjugats and malonic dialdehydes in the blood serum and the erythrocytes membranes before the operation and in postoperative period witness the lipid metabolism and the antioxidant defense system of organism changes.


Cooperative Interactions between 480 kDa Ankyrin-G and EB Proteins Assemble the Axon Initial Segment.
The axon initial segment (AIS) is required for generating action potentials and maintaining neuronal polarity. Significant progress has been made in deciphering the basic building blocks composing the AIS, but the underlying mechanisms required for AIS formation remains unclear. The scaffolding protein ankyrin-G is the master-organizer of the AIS. Microtubules and their interactors, particularly end-binding proteins (EBs), have emerged as potential key players in AIS formation. Here, we show that the longest isoform of ankyrin-G (480AnkG) selectively associates with EBs via its specific tail domain and that this interaction is crucial for AIS formation and neuronal polarity in cultured rodent hippocampal neurons. EBs are essential for 480AnkG localization and stabilization at the AIS, whereas 480AnkG is required for the specific accumulation of EBs in the proximal axon. Our findings thus provide a conceptual framework for understanding how the cooperative relationship between 480AnkG and EBs induces the assembly of microtubule-AIS structures in the proximal axon. Neuronal polarity is crucial for the proper function of neurons. The assembly of the axon initial segment (AIS), which is the hallmark of early neuronal polarization, relies on the longest 480 kDa ankyrin-G isoform. The microtubule cytoskeleton and its interacting proteins were suggested to be early key players in the process of AIS formation. In this study, we show that the crosstalk between 480 kDa ankyrin-G and the microtubule plus-end tracking proteins, EBs, at the proximal axon is decisive for AIS assembly and neuronal polarity. Our work thus provides insight into the functional mechanisms used by 480 kDa ankyrin-G to drive the AIS formation and thereby to establish neuronal polarity.