Syndromology: an updated conceptual overview. VIII. Deformations and disruptions.
A deformation is an abnormal form or position of the body caused by nondisruptive mechanical forces. Clubfoot, congenital hip dislocation, and infantile mandibular asymmetry (not based on mandibular malformation) serve as examples. The musculoskeletal system is involved in almost all deformations. Various disturbances of intrauterine movement are the usual causes and commonly occur during the fetal period. Causes may be mechanical or malformational. The former includes first pregnancies, small maternal size, uterine malformations and tumors, and amnionic rupture leading to oligohydramnios. Malformational causes usually involve the urogenital system and the central nervous system. A disruption is a morphologic defect of an organ, part of an organ, or a larger region of the body resulting from a breakdown of, or interference with, an originally normal developmental process. Amnionic band disruptions with digital amputations serve as an example. The most recent studies of disruptions and their suggested mechanisms are discussed. Finally, the interrelationships between malformations, deformations, and disruptions are explained.


Corrigendum to "Crinum jagus (J. Thomps. Dandy): Antioxidant and protective properties as a medicinal plant on toluene-induced oxidative stress damages in liver and kidney of rats" [Toxicol. Rep. 9 (2022) 699-712].
[This corrects the article DOI: 10.1016/j.toxrep.2022.03.026.].


Temporal trends in the prevalence and outcomes of geriatric patients with acute myocardial infarction in Japan-A report from the Miyagi AMI Registry Study.
Along with the global aging, the number of geriatric patients with acute myocardial infarction (AMI) has been increasing. However, temporal trends in the prevalence and outcomes of geriatric patients with AMI, with a special reference to heart failure (HF) on admission, remain to be elucidated. The Miyagi AMI Registry is a prospective, multicenter, and observational study. This registry was established in 1979 and has been continued for 40 years. We examined a total of 6,596 AMI patients aged ≥70 years (male/female 4,141/2,455) registered in this registry from 2005 to 2016 and divided them into 3 groups according to age [70-79 (n = 3,485), 80-89 (n = 2,601), and ≥90 years (n = 510)]. Of those, 17.6% had HF (Killip class ≥ II) on admission, for which age, female sex, diabetes, and previous MI were identified as independent predictors. Importantly, the prevalence of HF on admission significantly increased in all ages during the study period (all p for trend <0.01). Despite the presence of HF on admission, primary percutaneous coronary intervention (PCI) was performed in about 70% of patients aged in their 80 s and about half of those aged ≥90 years. In each group, performance rate of primary PCI also progressively increased (all p < 0.05) irrespective of concomitant HF. However, in-hospital mortality remained unchanged. Multivariable analysis demonstrated that, even for patients with HF on admission, primary PCI was associated with improved in-hospital mortality in the younger 2 groups [adjusted odds ratios (ORs), 95% confidence intervals (CI) 0.58 (0.36-0.93) for 70s, 0.64 (0.43-0.95) for 80s, and 0.99 (0.44-2.21) for ≥90s], whereas PCI was ineffective to reduce long-term hospitalization ≥30 days in all groups [adjusted ORs (95%CI) 0.90 (0.52-1.54), 0.66 (0.38-1.14), and 0.38 (0.07-2.10)]. These results demonstrate that increasing prevalence of HF on admission and increasing performance of primary PCI counteract each other with resultant unchanged in-hospital outcomes in geriatric AMI patients in Japan.


Studies on the turnover of endogenous choline-containing phospholipids of cultured neuroblastoma cells.
Previous studies on neuroblastoma cells in culture showed that the presence of partially purified rat liver phospholipid-transfer protein had a marked differential effect on the uptake and apparent subcellular distribution of radioactively labeled sphingomyelin and phosphatidylcholine (PC) added to the medium as mixed phospholipid (PC/sphingomyelin) liposomes. To determine the effect of phospholipid-transfer protein and exogenous phospholipids on the turnover and subcellular distribution of endogenous phospholipids, neuroblastoma cells were preincubated for 48 h in the presence of [methyl-3H]choline and washed. Aliquots of prelabeled cells were reincubated immediately in medium containing phospholipid-transfer protein mixed phospholipid liposomes, cytochalasin B and 2-deoxyglucose for 45 min at 37 degrees C; additional aliquots were chased first for 2 or 18 h with unlabeled choline before reincubation. The extent of labeled phospholipid degradation and accumulation in the medium, and the subcellular distribution of cell-associated labeled choline-containing phospholipids were determined. During incubation with phospholipid-transfer protein and mixed phospholipid liposomes, 25-35% of the cell-associated radioactive label from prelabeled cells, chased or unchased, was lost to the medium in 45 min. Over 50% of the label appearing in the medium was in water-soluble phospholipid degradation products. The loss of cell-associated label into the medium from unchased cells was stimulated significantly by phospholipid-transfer protein; however, prelabeled cells which had been chased for 18 h with unlabeled choline were unaffected by the presence of transfer protein. Endogenously synthesized radioactively labeled PC and sphingomyelin were distributed throughout all subcellular membranes, but least of all in the crude mitochondrial membrane fraction. Analysis of the subcellular distribution of cell-associated label remaining in chased or unchased cells after 45 min incubation with PC/sphingomyelin liposomes showed proportionate losses from all membrane fractions, except the crude mitochondrial fraction, which showed relative retention of labeled phospholipid. Phospholipid-transfer protein had no effect. The results are in distinct contrast to observations on the turnover, metabolism and subcellular distribution of labeled exogenous phospholipids under the same conditions, indicating that exogenous phospholipids do not intermix freely with any quantitatively major pool of endogenous phospholipid.


Prediction of internal arterial diameter from measurement of external diameter.
Internal and external diameters of sections of radial and ulnar arteries obtained from fresh cadavers were measured. Statistical analysis of the results obtained shows significant correlation (p less than 0.05). The wide range of values obtained suggests that, despite this degree of correlation, the internal diameter of an artery cannot be accurately predicted from the external diameter.


Reading-related wavelength and spatial frequency effects in visual spatial location.
Specific deficits in the processing of transient visual stimuli have been identified in reading-disabled children, and it has been shown that the filtering out of some medium to high spatial frequencies and some visible wavelengths impacts on their performance in a number of visual tasks. To assess further how these light diffusing and colour filtering manipulations might mediate visual processing, this study compared the letter-naming accuracy and visual spatial location judgements of eighteen poor readers with those made by eighteen good readers of the same age. Naming and spatial discrepancy measures were recorded for briefly displayed target letters at varying eccentricities, for each child, under a normal (NI) condition and wearing blue (Be), yellow (Yw), diffusion (Dn), blue with diffusion (BeDn), and yellow with diffusion (YwDn) optical framed lenses. A preliminary analysis of the data detected larger spatial discrepancies for the poor readers, and this finding was consistent with the presence of a deficit in transient (or magnocellular) activity in these children. Both the naming accuracy data and the spatial location data showed filter-dependent differences in reading ability. The letter-naming data showed that the addition of the blue filter to the diffusion lens significantly depressed performance only for the good readers, and that the addition of the yellow filter to the diffusion lens significantly improved performance only for the poor readers. Comparison of the spatial discrepancies showed that the rate at which location accuracy declined with increasing target eccentricity was smaller for the blue and yellow lenses than for normal viewing in the case of the good readers but not in the case of the poor readers.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cytotoxic antibodies against tumor cells in the blood of intact C3H mice].
Cytotoxic antibodies against mouse mammary tumour cells, L-cells and hepatoma 22a cells have been found in the serum of C3H/f and C3H/He mice over 8 months of age. Analogues antibodies were found in the serum of young and old BALB/c mice, but not in C57BL/6 mice. The cytotoxic activity of antimammary tumour cell serum has been completely abolished by its depletion by renal tissue of syngeneic and allogeneic animals.


Improving the understanding of medication non-adherence among mental health professionals: findings from a series of UK training workshops.
Medication non-adherence has far-reaching consequences. Before utilising specialized interventions to target this problem, there is a need to improve the detection, understanding and management of non-adherence in routine clinical practice. This study explored whether a 1-day workshop targeting attitudes, skills and knowledge about medication adherence could modify any aspect of clinical practice of mental health professionals. Five workshops were held with 134 participants. Baseline general knowledge in all professional groups was poor and interventions used not ideal. Post-workshop knowledge improved significantly. At 3-month follow-up, participants reported identifying more new cases of non-adherence and use of more effective strategies. Lack of time and support were identified as persisting barriers to change. It is possible to raise awareness, teach a model and simple techniques to effect change in clinical practice. This brief training was well received, although ongoing support is required to increase interventions for as well as identification of individuals at risk of medication non-adherence.


Stem cell-based cellular replacement strategies following traumatic brain injury (TBI).
Given the limited capacity of the central nervous system for self-repair, the use of stem cells holds an enormous potential in cell replacement therapy following traumatic brain injury and has thus received a great deal of scientific and public interest in recent years. During the past decade, several stem/progenitor cell types and lines from various sources such as embryonic rodent and human stem cells, immortalized progenitor cells, bone marrow derived cells or even post-mitotic neurons derived from human teratocarcinoma cells have been assessed for their potential to improve neurofunctional and behavioural outcome after transplantation into the experimentally injured brain. A number of studies indicate that cells engrafted into the injured brain can survive and, at least in part, may reverse behavioural dysfunction and histomorphological damage. Although these results emphasized their potential therapeutic role in traumatic brain injury, the detailed mechansim on how stem cells generate their mode of action, e.g. via integration into surviving neuronal circuits, local trophic support, or modification of the local mircoenvironment to enhance endogenous regeneration and potection remain yet to be identified. A review on current pre-clinical knowledge with respect to cellular replacement into the experimentally injured brain is presented.


Two-step enzymatic synthesis of UDP-N-acetylgalactosamine.
UDP-GalNAc has been synthesised with high yield from GalNAc, UTP and ATP using recombinant human GalNAc kinase GK2 and UDP-GalNAc pyrophosphorylase AGX1. Both enzymes have been prepared in one step from 1L cultures of transformed Escherichia coli and the UDP-GalNAc produced has been purified by a simple procedure. The method described is a rapid and efficient means to produce UDP-GalNAc as well as analogues like UDP-N-azidoacetylgalactosamine (UDP-GalNAz).


About PAR: the distinct evolutionary dynamics of the pseudoautosomal region.
Sex chromosomes differ from other chromosomes in the striking divergence they often show in size, structure, and gene content. Not only do they possess genes controlling sex determination that are restricted to either the X or Y (or Z or W) chromosomes, but in many taxa they also include recombining regions. In these 'pseudoautosomal regions' (PARs), sequence homology is maintained by meiotic pairing and exchange in the heterogametic sex. PARs are unique genomic regions, exhibiting some features of autosomes, but they are also influenced by their partial sex linkage. Here we review the distribution and structure of PARs among animals and plants, the theoretical predictions concerning their evolutionary dynamics, the reasons for their persistence, and the diversity and content of genes that reside within them. It is now clear that the evolution of the PAR differs in important ways from that of genes in either the non-recombining regions of sex chromosomes or the autosomes.


A theoretical study on the filtration efficiency and dust holding performance of pleated air filters.
Filter media composed of electrostatically charged nonwovens is the key device in an air purifier. Pleated filters are constructed from a cardboard frame with lattice faces containing a filter media reinforce by an expanded support grid, which have more surface area for trapping contaminants and capture airborne contaminants more effectively than non-pleated air filters. The aim of this work is to investigate the dominant factors on the filtration efficiency and dust holding performance of pleated filter by using a modified numerical model. It is found that geometric parameters of pleated filter play important roles to efficiency of the air purifier based on particle loading and filtration efficiency. The stable structural parameters include bending angle of pleated filter material in the range of 0∼60° and the ratio of bending portion less than 0.5. Lower filling degree and shorter length of pleated filter unit exhibit similar stability of efficiency, indicating that the change of structural parameters has little effects on the filtration performance. The knowledge obtained in this work provides concrete reference for the design of high-performance air-cleaner element.


Dansylation of human serum albumin in the study of the primary binding sites of bilirubin and L-tryptophan.
Binding of bilirubin and of L-tryptophan to dansylated albumins was investigated. Dansylation of less than one lysine residue per molecule of albumin did not affect the bilirubin binding, but decreased the L-tryptophan binding, indicating that dansylation had taken place in or near the l-tryptophan-binding site. Native albumin and albumin-bilirubin 1:1 complex showed the same affinity for L-tryptophan. The results indicate that, although L-tryptophan and bilirubin are bound in the same region, perhaps in a common cavity of the albumin molecule, such a cavity is sufficiently large to contain both ligands.


Anterior proliferative vitreoretinopathy.
During a four-year period, 53 of 92 eyes (58%) undergoing vitreoretinal surgery for a retinal detachment with proliferative vitreoretinopathy demonstrated anterior proliferative vitreoretinopathy. We classified anterior proliferative vitreoretinopathy according to tractional direction, location, extent, and severity. Initially, the eyes were treated with a high scleral buckle and laser endophotocoagulation as an adjunct to vitrectomy. Treatment then evolved into a direct approach in which the anterior proliferative tissue was surgically cut or excised. Of the 42 eyes followed up for at least six months, 25 (59%) were totally reattached and 18 (43%) had a visual acuity of 5/200 or better.


Tailoring the properties of mPEG-PLLA nanoparticles for better encapsulation and tuned release of the hydrophilic anticancer drug.
Gemcitabine is used as a first-line drug for treating many solid tumours. However, it suffers from a major drawback of strong side effects and short plasma half-life because of degradation by enzyme when administered intravenously. Polyesters and copolyesters are the most widely used and preferred class of biodegradable polymer. In the present work, efforts have been made to prepare poly(ethylene glycol) monomethoxy ether-poly(L-lactide) (mPEG-PLLA), a biodegradable amphiphilic copolymer with a view to improve the entrapment and tuned release of hydrophilic drug gemcitabine. The different mPEG-PLLA copolymers were synthesized with the varying ratios of mPEG and characterized by different techniques namely FTIR and 1H NMR spectroscopy, solution viscosity, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC). Gemcitabine-loaded nanoparticles were prepared using mPEG-PLLA copolymers by two methods i.e. nanoprecipitation and double emulsion solvent evaporation. The nanoprecipitation method showed very less entrapment and polymer solubility in the acetone-water mixture leading to uncontrolled polymer precipitation. The difficulties encountered in the nanoprecipitation method were overcome with the help of the double emulsion (w/o/w) solvent evaporation technique. It has been observed from the results that biodegradable copolymer nanoparticles protect the drug from degradation and also help in controlling the release of encapsulated drug. The properties of nanoparticles can be tailored by varying the composition of mPEG in order to get improved entrapment efficiency and desired drug release. The nanoparticles were assessed for their in vitro cytotoxicity (MTT and FACS) and cellular uptake (fluorescence microscopy) study which showed very promising results. Nanoparticles were also studied for their in vivo release after intravenous administration to Wistar albino rats, which successfully showed controlled drug release for more than 14 days.


Glycogen content of placenta and of fetal and maternal liver in cadmium-exposed rats. I: A descriptive light microscopic study.
Female Wistar rats were injected subcutaneously with CdCl2 (0.49 mg Cd/kg/day) daily during pregnancy. Placentae, fetal livers and maternal livers were prepared for histological investigation of the glycogen content 14, 16, 18, 19 and 20 days after mating. The glycogen content was estimated semiquantitatively in periodic acid-Schiff-(PAS-)stained sections. The development of the glycogen content of the placenta and the fetal liver from days 14 to 20 of pregnancy in control animals is described and compared with the development of the glycogen content of these tissues from cadmium-exposed animals. No clear changes due to cadmium exposure were observed in the glycogen content of maternal and fetal livers, nor in the spongiotrophoblast and the islets of glycogen in the placenta. The glycogen content in the placental labyrinth increased from day 14 up to day 18 in both control and cadmium-exposed animals. In control animals, the glycogen content decreased after day 18, whereas it remained high in the placental labyrinth of cadmium-exposed animals; this might be considered as a feature of retarded maturation. Regulating mechanisms and similarities between the effects of cadmium exposure and the diabetic state are discussed.


Radioiodine (131I) accumulation in bronchogenic cyst in the setting of thyroid carcinoma remission.
A 76-year-old woman had (131)I accumulation within the mediastinum in the setting of thyroid carcinoma remission. Extensive diagnostic imaging including computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound, bronchoscopy, and subsequently a needle aspiration biopsy revealed that the mass was a bronchogenic cyst. Five-year clinical and laboratory follow-up showed that the patient was free from thyroid carcinoma recurrence.


Risk factors for robot-assisted spinal pedicle screw malposition.
The accuracy of robot-assisted pedicle screw placement is unstable and remains controversial. The purpose of this study was to determine the risk factors for unsatisfactory Renaissance robot-assisted pedicle screw placement. This was a retrospective study of prospective data. From January 2017 to March 2018, 136 robot-assisted pedicle screw placements were performed in our department for spinal diseases, and a total of 874 screws were evaluated. All screws were assessed by the Gertzbein and Robbins classification. A and B were defined as satisfactory. C, D, and E were defined as unsatisfactory. Intraoperative registration failures due to nontechnical reasons or intraoperative adjustment were also defined as unsatisfactory. According to the evaluated results, the screws were divided into the satisfactory group (Group A) and the unsatisfactory group (Group B). The satisfactory rate was defined as satisfactory screws (the screws in Group A)/total screws, and the accurate rate was defined as accuracy screws (the screws in Group A)/the screws implanted by the robot (total screws - failed registration screws - screws adjusted during the operation). The age, sex, BMI, and BMD as well as the type of disease, the degree of vertebral rotation and the type of screw placement (percutaneous implantation or open implantation) were compared between the two groups, with the assessment of potential risk factors for unsatisfactory robot-assisted screw placement using logistic regression. A total of 874 screws were evaluated; there were 759 screws in Group A and 115 screws in Group B. The satisfactory rate was 86.8% (759/874), and the accuracy rate of the robot-placed screws was 94.4% (759/804). After logistic regression analysis, the independent risk factors were identified as obesity (OR 5.357 [95% CI 2.897-9.906], p < 0.01), osteoporosis, vertebral rotation and the presence of congenital scoliosis (OR 9.835 [95% CI 4.279-22.604], p < 0.01), particularly for severe osteoporosis (T < -3.5) and severe vertebral rotation (III-IV). According to the results of this study, obesity, osteoporosis and congenital scoliosis are risk factors for unsatisfactory robot-assisted screw placement. Furthermore, for surgeons in the initial stage of using a robot, we suggest avoiding cases in which a single risk factor or multiple risk factors exist to ensure the safety of the operation and to help augment the confidence of the surgeons.


Estimating the Cost of 3 Risk Prediction Strategies for Potential Use in the United Kingdom National Breast Screening Program.
Economic evaluations have suggested that risk-stratified breast cancer screening may be cost-effective but have used assumptions to estimate the cost of risk prediction. The aim of this study was to identify and quantify the resource use and associated costs required to introduce a breast cancer risk-stratification approach into the English national breast screening program. A micro-costing study, conducted alongside a cohort-based prospective trial (BC-PREDICT), identified the resource use and cost per individual (£; 2021 price year) of providing a risk-stratification strategy at a woman's first mammography. Costs were calculated for 3 risk-stratification approaches: Tyrer-Cuzick survey, Tyrer-Cuzick with Volpara breast-density measurement, and Tyrer-Cuzick with Volpara breast-density measurement and testing for 142 single nucleotide polymorphisms (SNP). Costs were determined for the intervention as implemented in the trial and in the health service. The cost of providing the risk-stratification strategy was calculated to be £16.45 for the Tyrer-Cuzick survey approach, £21.82 for the Tyrer-Cuzick with Volpara breast-density measurement, and £102.22 for the Tyrer-Cuzick with Volpara breast-density measurement and SNP testing. This study did not use formal expert elicitation methods to synthesize estimates. The costs of risk prediction using a survey and breast density measurement were low, but adding SNP testing substantially increases costs. Implementation issues present in the trial may also significantly increase the cost of risk prediction. This is the first study to robustly estimate the cost of risk-stratification for breast cancer screening. The cost of risk prediction using questionnaires and automated breast density measurement was low, but full economic evaluations including accurate costs are required to provide evidence of the cost-effectiveness of risk-stratified breast cancer screening. Economic evaluations have suggested that risk-stratified breast cancer screening may be a cost-effective use of resources in the United Kingdom.Current estimates of the cost of risk stratification are based on pragmatic assumptions.This study provides estimates of the cost of risk stratification using 3 strategies and when these strategies are implemented perfectly and imperfectly in the health system.The cost of risk stratification is relatively low unless single nucleotide polymorphisms are included in the strategy.


Infrared spectral characterization of peptidic material produced by ionizing radiation in aqueous cyanides.
Oligomers formed by ionizing radiation in aqueous cyanide solutions, under various experimental conditions, have been characterized by infrared spectroscopy. IR bands appear in the region known to be characteristic for amides and peptides. The results are discussed in relation to radiation-induced formation of peptidic material and the potential role of ionizing radiation as an energy source for some processes in prebiotic molecular evolution.


Design, synthesis and antitumor evaluation of novel thalidomide dithiocarbamate and dithioate analogs against Ehrlich ascites carcinoma-induced solid tumor in Swiss albino mice.
A series of 16 novel thalidomide sulfur analogs containing one and two sulfur atoms 2 and 4-18, respectively, were designed and synthesized. These compounds were screened for in vitro antitumor activity against Ehrlich ascites carcinoma (EAC) cell line and exhibited potent cytotoxic activity. On the bases of the obtained results for in vitro cytotoxic activity, thalidomide sulfur analogs containing two sulfur atoms 8, 9, 13 and 14 were selected and tested in vivo against EAC-induced solid tumor in female mice compared to thalidomide 1 as well as its analog 2 and exhibited a highly significant reduction in tumor volume (TV). Results illustrated the antioxidative activity of these compounds as the level of hepatic lipid peroxidation decreased and levels of antioxidant enzymes like superoxide dismutase (SOD) and catalase were elevated. The histopathological investigations revealed that thalidomide sulfur analogs 2, 8, 9, 13 and 14 have antimitotic, apoptotic and necrotic activities against solid tumor. These compounds lead to increase of Fas-L expression. The immunohistochemical studies showed a decrease in Ki67 and vascular endothelial growth factor (VEGF) staining in tumor cells from treated-animals when compared with non-treated groups, which suggests an inhibition of tumor proliferation rate and angiogenic process associated with tumor growth. Compounds 9 and 13 were the most potent compounds in tumor necrosis without liver necrosis. At the same time, treatment with compound 9 resulted in liver degeneration.


[Effectiveness of local delivery of ofloxacin using controlled-release strips (PT-01) in periodontal patients. Part 2. Successive delivery system and combination with scaling].
Four different sites were randomly selected in each periodontal patient and divided into four group: PT-01-treated site (A), PT-01 treatment combined with scaling (S + A), placebo-treated site (P) and placebo treatment combined with scaling (S + P). PT-01 and the placebo were applied to the periodontal pocket weekly on days 0 to 28, and clinical and microbiological evaluations were made. The results obtained were as follows: 1. Weekly changes in plaque index, plus discharge and mobility of the tooth were not observed in any group. 2. In gingival index, bleeding on probing, pocket depth and gingival crevicular fluid, significant improvement was found in A in comparison with P and in S + A in comparison with S + P. 3. In total number of subgingival bacteria and in the ratio of motile rods and spirochetes to the total number of bacteria, significant reduction was found in A in comparison with P and in S + A in comparison with S + P.


Estradiol selectively affects processing of conspecifics' faces in female rhesus monkeys.
Estrogen deficiency following ovariectomy or menopause increases the risk of developing diseases such as osteoporosis and may also lead to memory impairment. Although estrogen replacement therapy (ERT) alleviates many symptoms associated with estrogen loss, it is not clear whether it also benefits cognitive function. The effect of estrogens upon cognition can best be studied in an animal model of human menopause, in which estrogen levels can be experimentally manipulated. Six young ovariectomized female rhesus monkeys (6-9 years old) were tested on a battery of touchscreen-based cognitive tasks, including the Matching-to-Sample (MTS) task with mixed delays and the spatial, object, and face conditions of the Delayed Recognition Span Test (DRST). Monkeys were tested 5 days a week, one task per week, for a total of 8 months, while undergoing treatments with placebo and ethinyl estradiol (EE2) in alternating 28-days blocks. Blood samples were collected to verify EE2 levels. We also observed the monkeys by video monitor during test sessions and recorded locomotor activity and response topology. Performance on the face-DRST, a task that involved selecting the new face in an increasing array of rhesus monkey faces, was impaired by EE2 treatment, as compared to placebo. Other tasks were unaffected by EE2. There was no clear evidence of EE2 effects upon motor activity or anxiety. In order to test the reliability of our findings, we conducted an additional experiment in which the monkeys were again given the face-DRST with different categories of face stimuli for 4 months, while receiving placebo and EE2 in alternating 7-days blocks. They performed each task 4-5 days/week for 4 weeks with (1) the same rhesus monkey faces as in the first experiment, (2) human faces, (3) chimpanzee faces, and (4) novel rhesus monkey faces. Face-DRST performance did not vary as a function of treatment when human or chimpanzee faces were used as stimuli. In contrast, periods of EE2 treatment were associated with a lower performance for both sets of rhesus monkey faces. These findings suggest that EE2 treatment has a detrimental effect on processing faces of conspecifics by female rhesus monkeys. We speculate that estrogens may produce this effect by enhancing emotional reactivity to socially relevant stimuli.


Behavioral pharmacology and timing.
Drug effects on temporally patterned behavior are often described under the rubric of rate dependency: the effect of a drug on behavior is related to the rate of behavior in the absence of the drug. Specifically, drugs increase low rate behavior and decrease high rate behavior. These same types of effects are interpreted in the timing literature, however, as selective changes in temporal discrimination. The present series of experiments arrange situations that allow divergent predictions based on the two interpretations. In one component of a multiple schedule, when the response key is lit blue, food is available after the houselight is presented for a short duration (5 s). In the other component of the multiple schedule, when the response key is lit green, food is available after the houselight is presented for a long duration (30 s). No food is available after intermediate durations. Specific focus is given to a neuropharmacological information-processing model of timing. Predictions were compared for drugs that are thought to affect the clock and memory stages in the model. The results do not generally lend support for the neuropharmacological interpretation of the scalar expectancy theory, but emphasize the need for an explanatory mechanism that is consistent with the empirical generalization of rate dependency.


Types and characteristics of ramp-related motor vehicle crashes on urban interstate roadways in Northern Virginia.
Freeway entrance and exit ramp interchanges are the sites of far more crashes per mile driven than other segments of interstate highways, but the characteristics and circumstances of ramp crashes have been the subject of relatively little recent research. This study examined a sample of 1,150 crashes that occurred on heavily traveled urban interstate ramps in Northern Virginia. Based on a review of diagrams and narrative descriptions from police crash reports, the most common crash types were identified and examined for different roadway locations and ramp designs and by whether at-fault drivers were entering or exiting the freeway. About half of all crashes occurred when at-fault drivers were in the process of exiting interstates, 36% occurred when drivers were entering, and 16% occurred at the midpoints of access roads or on ramps connecting two interstate freeways. Three major crash types--run-off-road, rear-end, and sideswipe/cutoff--accounted for 95% of crashes in the study. The crash type most frequently associated with exiting was run-off-road, and the types most common with entering drivers were rear-end or sideswipe/cutoff. Crashes most common on ramps--run-off-road crashes--frequently occurred when vehicles were exiting interstates at night, in bad weather, or on curved portions of ramps. Speed was often a factor. Crashes occurring on ramp margins (where ramps or access roads enter or exit) were most commonly of the sideswipe/cutoff type. These often involved at-fault passenger vehicles merging from entrance ramps into the sides of large trucks already on the freeway. The predominant crash type on access roads was rear-end crashes; congestion was a factor in these crashes. Alcohol was a reported factor in a sizeable proportion of run-off-road crashes occurring on ramps (14%) and ramp margins (30%). Candidate countermeasures for run-off-road crashes include geometric design changes to increase ramp design speed such as increasing curve radii. Speed-related crashes may be reduced by the use of speed cameras accompanied by publicity. Rear-end crash countermeasures could include surveillance systems that quickly detect unexpected congestion, incident response programs, and variable message signs to alert drivers to traffic congestion ahead. Countermeasures for sideswipe/cutoff crashes could include extending the length of acceleration lanes.


Distribution of a vaginal gel (Invisible Condom) before, during and after simulated sexual intercourse and its persistence when delivered by two different vaginal applicators: a magnetic resonance imaging study.
The objective of this study was to evaluate the vaginal distribution of a microbicidal gel (Invisible Condom) before, during and after simulated intercourse using an artificial phallus. The gel was delivered using either a new proprietary vaginal applicator (PVA), which has multiple lateral and apical holes, or a commercial applicator (CA), which has a single apical hole. The persistence of the gel was evaluated up to 24 h after its administration. Nine women (five women using the PVA and four women using the CA) applied the vaginal gel once, and pelvic images were taken immediately after application. An artificial phallus was inserted and the women had 30 vaginal thrusts, then another set of images was taken while the phallus was still inside the vagina. On exit of the phallus, one more set of images was taken. Images were subsequently taken at 30 min, 2 h, 6 h and 24 h after gel application. Immediately after gel application, the PVA distributed the gel throughout the vaginal/cervical mucosae, while the CA delivered the gel only to the cervical area. During simulated intercourse, the phallus further pushed the gel delivered with the CA into the fornix, whereas it spread the gel delivered with the PVA more evenly throughout the mucosal surface. After simulated intercourse, both applicators gave similar gel distributions between 30 min and 6 h after application. However, at 24 h, using the PVA, only 5% of the gel persisted in the vagina, compared to 40% of the gel using the CA. Using the new PVA, the Invisible Condom covered the vaginal/cervical mucosae before and during simulated intercourse, offering immediate protection, whereas only the cervical mucosa was covered using the CA. Forty percent of the gel persisted mostly in the upper vaginal/cervical area at 24 h following its administration with the CA, while only 5% of the gel was left using the PVA. The new applicator, with its unique design, ensures an even and immediate coating lasting throughout the first 6 h and could prevent potential microbicide vaginal toxicity at 24 h.


Inhibition of microRNA-19a-3p alleviates the neuropathic pain (NP) in rats after chronic constriction injury (CCI) via targeting KLF7.
Neuropathic pain(NP) is derived from the dysfunctions of nerve system. The current research is to explore the impact and mechanism of miR-19a-3p in neuropathic pain in rats. The NP was induced through the chronic constriction injury (CCI) surgery in rats. The pro-inflammatory factors (IL-1β, IL-6, TNF-α) in spinal cord tissues from rats were measured using Elisa kits. Moreover, the different levels of thermal hyperalgesia and mechanical allodynia in rats were examined through paw withdrawal latency (PWL) and paw withdrawal threshold (PWT). To investigate into the role of miR-19a-3p and KLF7 in NP of rats, the knockdown of miR-19a-3p alone or along with KLF7 downregulation in rats were achieved through lentivirus injection. The miR-19a-3p and KLF7 expression in spinal cord of rats on Day 3,7,14 after CCI were detected using RT-qPCR. The protein expression of KLF7 were measured by Western blot. Bioinformatics and luciferase assays were used for the prediction and verification of bindings between KLF7 and miR-19a-3p. CCI surgery caused neuropathic pain in rats with the levels of inflammatory cytokines increased and PWL and PWT decreased. Moreover, miR-19a-3p expression was increased while the protein and mRNA levels were decreased in spinal cord tissues in rats after CCI surgery. In rat microglial cells, miR-19a-3p downregulation could promote the KLF7 in both mRNA and protein expression. In spinal cord tissues of rats, the inhibition of miR-19a-3p enhanced the KLF7 expression. Furthermore, miR-19a-3p downregulation suppressed the IL-1β, IL-6 and TNF-α concentrations, and could decrease the NP but inhibition of KLF7 could partially reverse this in CCI rats. miR-19a-3p inhibition may alleviate NP via KLF7 in CCI rats.


The relevance of mitochondrial membrane topology to mitochondrial function.
This review summarizes recent findings from electron tomography about the three-dimensional shape of mitochondrial membranes and its possible influence on a range of mitochondrial functions. The inner membrane invaginations called cristae are pleomorphic, typically connected by narrow tubular junctions of variable length to the inner boundary membrane. This design may restrict intra-mitochondrial diffusion of metabolites such as ADP, and of soluble proteins such as cytochrome c. Tomographic images of a variety of mitochondria suggest that inner membrane topology reflects a balance between membrane fusion and fission. Proteins that can affect cristae morphology include tBid, which triggers cytochrome c release in apoptosis, and the dynamin-like protein Mgm1, involved in inter-mitochondrial membrane fusion. In frozen-hydrated rat-liver mitochondria, the space between the inner and outer membranes contains 10-15 nm particles that may represent macromolecular complexes involved in activities that span the two membranes.


Aquareovirus protein VP6 colocalizes with NS80 protein in infected and transfected cells.
Aquareovirus particle is comprised of central core and outer capsid, which is built by seven structural proteins (VP1-VP7). The protein VP6 has been identified to be a clamp protein of stabilizing inner core frame VP3, and bridging outer shell protein VP5. However, the biological properties of VP6 in viral life cycle remain unknown. The recombinant VP6 (rVP6) of aquareovirus was expressed in E. coli, and the polyclonal antibody against VP6 was generated by using purified rVP6 in this study. Following the preparation of VP6 antibody, the VP6 component in aquareovirus infected cells and purified viral particles was detected by Immunoblotting (IB) assay. Furthermore, using Immunofluorescence (IF) microscopy, singly transfected VP6 protein was observed to exhibit a diffuse distribution mainly in the cytoplasm, while it appeared inclusion phenotype in infected cells. Meanwhile, inclusion structures were also identified when VP6 was coexpressed with nonstructural protein NS80 in cotransfected cells. VP6 can be recruited by NS80 to its inclusions in both infected and transfected cells. The colocalization of VP6 and NS80 is corresponding to their homologous proteins σ2 and μNS in MRV. Our results suggest that VP6 may play a significant role in viral replication and particle assembly.


Organosulfur compounds alone or in combination with vitamin C protect towards N-nitrosopiperidine- and N-nitrosodibutylamine-induced oxidative DNA damage in HepG2 cells.
The aim of this study was to investigate the protective effects of organosulfur compounds (OSCs) alone or in combination with vitamin C towards N-nitrosopiperidine (NPIP) and N-nitrosodibutylamine (NDBA)-induced oxidative DNA damage in the single cell gel electrophoresis (SCGE)/HepG2 assay. Diallyl sulfide (DAS) did not protect against NDBA-induced oxidized purines, but it reduced the oxidized purines induced by NPIP (1 microM, 29%). The formation of formamidopyridine-DNA glycosylase (Fpg) sensitive sites induced by NPIP or NDBA was prevented by dipropyl sulfide (DPS) at concentrations of 1-10 microM (55-24% and 66-15%, respectively). The maximum reduction of the formation of Fpg sensitive sites induced by NPIP was observed at the highest concentration of diallyl disulfide (DADS) (2.5 microM, 38%). However, the oxidative DNA damage induced by NDBA was strongly reduced by DADS at the lowest concentration tested (0.1 microM, 92%). The oxidative DNA damage induced by NPIP or NDBA was prevented by all the concentrations of dipropyl disulfide (DPDS) (0.1-2.5 microM, 59-80% and 51-64%, respectively). DADS and DPDS, in combination with vitamin C showed an overall protective effect towards the formation of Fpg sensitive sites induced by NPIP and NDBA. However, the contribution of OSCs to the protective effect found in combined experiments might not be relevant, because it could be caused by vitamin C alone. One feasible mechanism by which OSCs exert their protective effects towards N-nitrosamine-induced oxidative DNA damage could be by modulation of phase I and II enzyme activities. DADS and DPDS (0.1-2.5 microM) exerted greater inhibition on CYP2E1 and CYP2A6 activity than DAS and DPS (1-50 microM). However, DAS and DADS (1 microM) exerted greater inhibition on CYP1A1 activity than DPS and DPDS (1 microM). DAS/DPS (50 microM) and DADS (2.5 microM) exerted a moderate increase of UDP-glucuronyltransferase (UGT1A4) activity, whereas DPDS (2.5 microM) had the most pronounced effect.


Identification and characterization of T-cell receptors with therapeutic potential showing conserved specificity against all SARS-CoV 2 strains.
Treatment of severe COVID-19 disease can be challenging in immunocompromized patients due to newly emerging virus variants of concern (VOC) escaping the humoral response. Thus, T cells recognizing to date unmutated epitopes are not only relevant for patients' immune responses against VOC, but might also serve as a therapeutic option for patients with severe COVID-19 disease in the future, e.g. following allogenic stem cell transplantation. To this purpose, the activation, cytokine profile and specificity of T-cell clones against unmutated and omicron Spike (S)-protein was analyzed, HLA restriction was determined and most promising T-cell receptor (TCR) was introduced into allogeneic T cells via CRISPR/Cas9-mediated orthotopic TCR replacement. Finally, T-cell responses of engineered T cells was determined and durability of the TCR replacement measured. SARS-CoV-2 specific engineered T cells recognizing a genomically stable region of the S-protein of all SARS-CoV 2 variants were successfully generated. Such transgenic T cells exhibit favorable effector functions and provide a treatment option of immunocompromised COVID-19 patients.


Payer and Implementation Challenges with Advanced Therapy Medicinal Products (ATMPs).
Advanced therapy medicinal products (ATMPs) are a dynamic and current topic for healthcare systems, with new products progressing to market at an increasing rate. ATMPs highlight the growing gap between payer and regulator requirements; the limited evidence base combined with pressure to implement rapidly is exacerbating the clinical and financial uncertainties associated with these products. There are a number of key uncertainties with ATMPs related to implementation and healthcare planning-these uncertainties at the time of evaluation have the ability to change the value proposition of products. ATMPs also have the potential to reduce the amount of net health gain available to healthcare systems, and evaluators should consider the opportunity cost when seeking to accelerate access to one-off therapies with a limited clinical evidence base. Therefore, ATMPs have the potential to transform clinical care pathways, but implementation challenges and application of key health economic principles may highlight the requirement to exercise caution.


Real-Time Spectral Library Matching for Sample Multiplexed Quantitative Proteomics.
Sample multiplexed quantitative proteomics assays have proved to be a highly versatile means to assay molecular phenotypes. Yet, stochastic precursor selection and precursor coisolation can dramatically reduce the efficiency of data acquisition and quantitative accuracy. To address this, intelligent data acquisition (IDA) strategies have recently been developed to improve instrument efficiency and quantitative accuracy for both discovery and targeted methods. Toward this end, we sought to develop and implement a new real-time spectral library searching (RTLS) workflow that could enable intelligent scan triggering and peak selection within milliseconds of scan acquisition. To ensure ease of use and general applicability, we built an application to read in diverse spectral libraries and file types from both empirical and predicted spectral libraries. We demonstrate that RTLS methods enable improved quantitation of multiplexed samples, particularly with consideration for quantitation from chimeric fragment spectra. We used RTLS to profile proteome responses to small molecule perturbations and were able to quantify up to 15% more significantly regulated proteins in half the gradient time compared to traditional methods. Taken together, the development of RTLS expands the IDA toolbox to improve instrument efficiency and quantitative accuracy for sample multiplexed analyses.


New 30-Noroleanane Triterpenoid Saponins from Holboellia coriacea Diels.
Three new 30-noroleanane triterpenoid saponins, akebonoic acid 28-O-β-d-glucopyranosyl-(1''→6')-β-d-glucopyranosyl ester (1), akebonoic acid 28-O-(6''-O-caffeoyl)-β-d-glucopyranosyl-(1''→6')-β-d-glucopyranosyl ester (Holboelliside A, 2) and 3β,20α,24-trihydroxy-29-norolean-12-en-28-oic acid 3-O-(6'-O-caffeoyl)-β-d-glucopyranoside (Holboelliside B, 3) were isolated from the stems of Holboellia coriacea Diels, together with five known compounds, eupteleasaponin VIII (4), 3α-akebonoic acid (5), quinatic acid (6), 3β-hydroxy-30-norhederagenin (7) and quinatoside A (8). The structures of these compounds were determined on the basis of spectral and chemical evidence. Compounds 1-5 were evaluated for their inhibitory activity against three human tumors HepG2, HCT116 and SGC-7901 cell lines in vitro.


Complications after nasal skin repair with local flaps and full-thickness skin grafts and implications of patients' contentment.
The range of complications after plastic surgical repair of nasal skin defects is not clearly known. The aim of this study was to identify complications after reconstruction of nasal skin defects to determine what typical complications occur after standard surgical options including full-thickness skin graft (FTSG) and local flap plastics (LFP). In 210 patients with defects of the nasal tip, the nasal ala or dorsum of the nose (average diameter 1.1 +/- 0.3 cm) surgical skin repair was performed with LFP or FTSG. Complications within 6 months after surgery were recorded. Some 41 patients (19.5%) suffered complications; there was no significant difference in total complication rate between LFP (20.5%) and FTSG (18.3%). However, FTSG patients had significantly more infections postoperatively than LFP patients (5.4% vs. 2.6%). LFP patients presented a significantly higher rate of wound or suture dehiscence (FTSG 2.2%, LFP 5.9%). FTSG patients exhibited a significantly higher rate of partial or complete loss (total rate FTSG 8.5%, LFP 5.2%). The LFP technique led to significantly more aesthetic deficits (FTSG 2.1%, LFP 6.8%). LFP showed advantages with regard to infection and loss rates but with a higher rate of aesthetic deficits compared to FTSG. It remains an individual decision as to which procedure is used to repair defects of the nose, depending on patient and surgical variables.


Comparative non-metric and morphometric analyses of rats at residential halls of the University of Benin campus, Nigeria.
In mammals and across rat species, the variation in conformation is markedly observed in the head and the variation in the shape of the head is mostly determined by the shape of the skull. Hence comparative topographic analysis and morphometry is a veritable tool in precise categorization of peri-domestic rats and species identification. Killed rodents around residential dwellings of students on campus were collected and measurements taken of external morphology. Thirty-one external head and corporal parameters; and 40 cranial measurements respectively were obtained. Topographic features and specific anatomical landmarks measured were matched using congruent anatomical landmarks and compared to referenced standard measurements. External morphometry suggests that all retrieved samples were more closely related to the species Rattus rattus. However, craniodental analysis of captured rats reveals variations from the mean of typical R. rattus. In comparison with Mastomys natalensis, the mean averages of the rat species were perceptibly different for only two of the parameters viz palatine fissure length (PL) (p=0.039) and distance between interparietal bone (DP) (p=0.06). In contrast, the mean of whole length of skull (WL), length of diastema (PI), length of nasal bone (NL), length of frontal bone (LF) and occipital width (OH) were significantly different from that of R. rattus with p values of 0.047, 0.036, 0.048, 0.032 and 0.034 respectively. This study focuses on peridomestic rat's identification within the University campus based on morphometry, providing unique landmarks for differentiation between Mastomys, Mus, Rattus and other rat species with emphasis on the need for more comprehensive investigation, categorization and morphometric profiling of rat population in Nigeria. Metric data generated for rat profiling in Nigeria is pivotal for a more comprehensive strategy for prevention of Lassa fever.


Spontaneous abdominal wall endometrioma: A case report.
The abdominal wall is the commonest site of extra pelvic endometriosis (endometrioma), defined as the presence of functional endometrial gland and stroma outside the uterine cavity. Spontaneous abdominal wall endometriosis (AWE) represents an ectopic functional endometrial tissue situated superficial to peritoneum in a scar less abdomen. Spontaneous AWE is rare, accounting for 20% of all abdominal wall endometriosis. It is unfamiliar to general surgeons because of a large number of potential pitfalls in its diagnosis. We report a case of spontaneous abdominal wall endometriosis (endometrioma) presenting to our general surgery clinic with a painful nodular mass in hypogastric area below umbilicus. The initial diagnosis was a desmoid tumour of the anterior abdominal wall. Pain was a remarkable complaint in our patient. Abdominal wall endometrioma was diagnosed by histopathology postoperatively. Excision planned, during operation, one mass was spotted and excised within healthy limits. Histopathology revealed: endometrial glands surrounded by mantle of endometrial stroma, few scattered hemosiderin laden macrophages and fibrous scar tissues. Our patient had no previous scar. She was discharged from hospital on 5th postoperative day uneventfully. (On account of uncontrolled DM and Hypertension). One year of follow up after the surgery, she is free from disease and no recurrence has been observed. Endometriosis is characterised by the presence of endometrial glands and stroma outside the uterine cavity with the maximum prevalence reported in the 4th decade of life. Most cases of spontaneous endometriosis occur in a scar less abdomen. Multiple imaging techniques have been used and described for its diagnosis. The alleged aetiopathogenesis of spontaneous endometrioma is still debatable. It is usually diagnosed by the histopathology and the preferential treatment in cases of endometrioma is total excision of the mass. The hormonal therapy can be added to surgical excision if there is proven pelvic endometriosis. The surgical excision should be wide enough to prevent its recurrence. Spontaneous abdominal wall endometriosis is an extremely rare gynaecological entity, accounts for 18-20% of all abdominal wall endometriosis. The diagnosis of abdominal wall endometrioma is hardly established prior to surgery. The triad: mass, pain and cyclic symptom aids in diagnosis, unfortunately cyclic symptom is not present in all cases (as in our case). Spontaneous abdominal wall endometrioma is usually diagnosed by high index of clinical suspicion and histopathology. The results of imaging techniques are nonspecific. It may pose a diagnostic dilemma due to its rarity and atypical presentation. The preferential treatment of choice is wide excision.


Measuring emotion recognition by people with Parkinson's disease using eye-tracking with dynamic facial expressions.
Motion is an important cue to emotion recognition, and it has been suggested that we recognize emotions via internal simulation of others' expressions. There is a reduction of facial expression in Parkinson's disease (PD), which may influence the ability to use motion to recognise emotions in others. However, the majority of previous work in PD has used only static expressions. Moreover, few studies have used eye-tracking to explore emotion processing in PD. We measured accuracy and eye movements in people with PD and healthy controls when identifying emotions from both static and dynamic facial expressions. The groups did not differ overall in emotion recognition accuracy, but motion significantly increased recognition only in the control group. Participants made fewer and longer fixations when viewing dynamic expressions, and interest area analysis revealed increased gaze to the mouth region and decreased gaze to the eyes for dynamic stimuli, although the latter was specific to the control group. Ours is the first study to directly compare recognition of static and dynamic emotional expressions in PD using eye-tracking, revealing subtle differences between groups that may otherwise be undetected. It is feasible and informative to use eye-tracking with dynamic expressions to investigate emotion recognition in PD. Our findings suggest that people with PD may differ from healthy older adults in how they utilise motion during facial emotion recognition. Nonetheless, gaze patterns indicate some effects of motion on emotional processing, highlighting the need for further investigation in this area.


Emergency surgery for tubo-ovarian abscess identified extended-spectrum beta-lactamase-producing Escherichia coli: the first case presentation revealing causative bacteria.
We report herein a 41-year-old female with a tubo-ovarian abscess (TOA), which microbial cultures showed to contain extended-spectrum beta-lactamase (ESBL)-producing E. coli, a causative agent of community-acquired infection. The patient initially presented with acute abdominal pain and back pain. Pelvic computed tomography and transvaginal ultrasonography revealed multiple cystic lesions in the bilateral ovaries that suggested TOA. An emergency laparotomy was therefore performed due to the potential for life-threatening septic shock from the TOA-associated pelvic inflammatory disease. Microbial cultures of postoperative fluid discharge from the placed intra-abdominal catheter, vaginal secretions, urine, blood, and feces detected ESBL-producing E.coli. In summary, we successfully performed emergency surgery for life-threatening septic TOA caused by ESBL-producing E. coli infection.


Radical perineal vs. retropubic prostatectomy: a review of optimal application and technical considerations in the utilization of these exposures.
Radical prostatectomy can be performed either with a retropubic or perineal approach. While the former has enjoyed popularity in recent years, perineal prostatectomy has undergone a substantial resurgence because of interest in laparoscopic pelvic lymphadenectomy. The advantages and disadvantages of each are defined, as well as technical modifications that have been developed seeking to diminish problems with each approach. While many urologic surgeons are no longer familiar with the perineal approach, its potential advantages, particularly in certain situations, would suggest that it can be a valuable component of the uro-oncologist's surgical armamentarium for the management of localized prostate cancer.


The usefulness of a repeat study for differentiating between bowel activity and local tumor recurrence on FDG PET scans.
The importance of fluorodeoxyglucose (FDG) positron emission tomography (PET) in the evaluation of colorectal cancer is well established. Activity in the rectosigmoid region on an FDG PET scan may vary significantly, which may occasionally lead to difficulties in interpretation when assessing local recurrence of colorectal cancer. The authors present a case in which a repeat PET study performed after an enema 1 week later was useful for differentiating between normal bowel activity and local tumor recurrence. This repeat study obviated the need for surgical intervention, although the role of the enema in this case is unclear.


The DNA binding and pairing preferences of the archaeal RadA protein demonstrate a universal characteristic of DNA strand exchange proteins.
The archaeal RadA protein is a homologue of the Escherichia coli RecA and Saccharomyces cerevisiae Rad51 proteins and possesses the same biochemical activities. Here, using in vitro selection, we show that the Sulfolobus solfataricus RadA protein displays the same preference as its homologues for binding to DNA sequences that are rich in G residues, and under-represented in A and C residues. The RadA protein also displays enhanced pairing activity with these in vitro-selected sequences. These parallels between the archaeal, eukaryal and bacterial proteins further extend the universal characteristics of DNA strand exchange proteins.


Total reconstruction of the vesico-urethral junction.
We describe a novel technique of total vesico-urethral reconstruction, which combines the tactics of previous surgeons, and compare the outcome of our innovative changes for return to early continence with prostatectomies with no or partial reconstruction of the vesico-urethral junction. Between 1 January 2005 and 5 June 2007 a cohort of 700 patients undergoing robotic radical prostatectomy were prospectively evaluated. Patients in 2005 (214) served as a control group, they received no additional methods to provide support to the vesico-urethral junction; a standard anastomosis was made. Patients in 2006 (304) received an anterior reconstruction only, to provide additional vesico-urethral anastomotic support. Patients in 2007 (182) received the total reconstructive procedure, which included an anterior reconstruction and posterior reconstruction. Outcome data were collected using standardized health-related quality-of-life measures, which included the Expanded Prostate Cancer Index Composite survey, International Prostate Symptom Score, International Index of Erectile Function, and then re-verified by telephone interview with a standardized questionnaire. The follow-up intervals were 1, 6, 12, 24 and 52 weeks. Continence was defined as no pad usage or one small liner used for security purposes only. Baseline variables were also collected. The percentage of patients who had achieved continence in the control group were: 13%, 35%, 50%, 62% and 82% at the 1-, 6-, 12-, 24- and 52-week follow-up, respectively. The percentage of patients who had achieved continence in the anterior reconstruction group were 27%, 59%, 77%, 86%, and 91%, respectively. The total reconstruction group had continence rates of 38%, 83%, 91%, and 97% at 1, 6, 12, and 24 weeks, respectively. At all the follow-up intervals the continence rate was significantly less in the control group than in the anterior reconstruction group and the total reconstruction group (P < 0.01). The total reconstruction procedure is a safe and effective way to achieve an early return to continence. No adverse effects have been observed because of its employment and our data validates that it does provide a statistically significant early return to continence compared with no reconstructive efforts or with only anterior reconstructive efforts.


Clinical pitfalls and serological diagnostics of MuSK myasthenia gravis.
We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG. A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups. After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen's kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation. While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice.


Potent and selective cathepsin K inhibitors.
A novel series of cathepsin K inhibitors derived from Novartis compound I is described. Optimization of the P1, P3, and P1' units led to the identification of 4-aminophenoxyacetic acid 24b with an IC(50) value of 4.8 nM, which possessed an excellent selectivity over other human cathepsins and good pharmacokinetic (PK) properties. Oral administration of compound 24b to ovariectomized (OVX) rats showed a trend toward an improvement of bone mineral density (BMD) in the femur bone.


Predictors of erectile dysfunction post pelvic fracture urethral injuries: a multivariate analysis.
To learn the incidence of erectile dysfunction (ED) after pelvic fracture urethral injury (PFUI) and to identify the related risk factors. Patients who had sustained a PFUI from 1984 to 2010 were identified from database and invited to participate in the study. All responders were queried after a minimum of 2 years from the time of trauma to assess their erectile function (EF) using the EF domain of the International Index of Erectile Function (IIEF). Medical records and imaging studies were reviewed with a focus on 6 variables that may predict ED. Univariate and multivariate analyses were used to identify parameters predictive of ED. Overall, 90 patients participated in the study, among whom 40 (44%) had ED. On univariate analysis, 4 variables were significant factors for prediction of ED, whereas on multivariate analysis only 3 factors remained strong and independent predictors, namely diastasis of pubic symphysis, lateral displacement of prostate, and long urethral gap. The results of analyses showed that these 3 variables were significant at odds ratios (ORs) of 15.9, 6.9, and 2.0, respectively. The development of ED after PFUI can be predicted by 3 factors, namely diastasis of pubic symphysis, lateral prostatic displacement, and long urethral gap. Pubic diastasis has the highest predictive accuracy. A tendency for higher risk of ED could be observed after bilateral rami and Malgaigne's fractures, but they failed to reach the level of significant predictors on multivariate analysis. No relationship was evidenced between ED and age at traumatism.


T-lymphocyte-expressing inflammatory cytokines underlie persistence of proteinuria in children with idiopathic nephrotic syndrome.
There is evidence of an important role of immune system changes in the triggering and maintenance of idiopathic nephrotic syndrome (INS). The aim of this study was to investigate the expression of cytokines in lymphocyte populations of patients with INS in comparison to healthy individuals, according to proteinuria. This cross-sectional study included 44 patients with INS and eight healthy children, matched for age and sex (controls). Patients were subdivided according to proteinuria: persistent proteinuria or partial remission (PP≥300mg/24h, n=17) and low proteinuria or complete remission (LP<300mg/24h, n=27). Ex vivo analysis of peripheral blood leukocytes by flow cytometry was performed using surface markers for T-lymphocytes, TCD4, TCD8, natural killer (NK) cells, NKT, and B-lymphocytes. Frequencies of intracellular cytokines were analyzed in these cells. The frequencies of B-lymphocytes, NK cells, and NKT cells were lower in INS than in controls, whereas INS patients had a higher frequency of CD4+tumor necrosis factor (TNF)-α+ cells than controls. Cytotoxic-T-lymphocytes expressing IFN-γ were lower in INS than in controls. Patients with PP showed higher frequencies of CD4-T-lymphocytes expressing IFN-γ and TNF-α than controls. CD8-lymphocytes expressing TNF-α were increased in PP group when compared with LP and controls, while CD8+interferon (IFN)-γ+ cells were lower than in LP and in controls. Regardless the level of proteinuria, INS patients had increased expression of TNF-α in CD4-lymphocytes and reduced expression of IFN-γ in CD8-lymphocytes. Persistence of proteinuria was associated with higher levels of inflammatory markers.


Pen-drawn Marangoni swimmer.
Pen-drawing is an intuitive, convenient, and creative fabrication method for delivering emergent and adaptive design to real devices. To demonstrate the application of pen-drawing to robot construction, we developed pen-drawn Marangoni swimmers that perform complex programmed tasks using a simple and accessible manufacturing process. By simply drawing on substrates using ink-based Marangoni fuel, the swimmers demonstrate advanced robotic motions such as polygon and star-shaped trajectories, and navigate through maze. The versatility of pen-drawing allows the integration of the swimmers with time-varying substrates, enabling multi-step motion tasks such as cargo delivery and return to the original place. We believe that our pen-based approach will significantly expand the potential applications of miniaturized swimming robots and provide new opportunities for simple robotic implementations.


Relative roles of ICAM-1 and VCAM-1 in the pathogenesis of experimental radiation-induced intestinal inflammation.
Cell adhesion molecules mediate leukocyte recruitment into the irradiated organs; modulation of this process may protect from radiation damage. Our objective was to characterize the requirement for intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in intestinal inflammatory response after abdominal irradiation. Endothelial ICAM-1 and VCAM-1 expression was determined using radiolabeled antibodies in mice 24 h and 14 days after irradiation with 10 Gy, or sham radiation. Leukocyte-endothelial cell interactions in intestinal venules were assessed using intravital microscopy, and the function of ICAM-1 and VCAM-1 in this process by using blocking antibodies and ICAM-1(-/-) mice. The number of adherent leukocytes significantly increased 24 h after irradiation and remained elevated at 14 days. Treatment with anti-ICAM-1 antibodies and ICAM-1 genetic deficiency significantly reduced leukocyte adhesion 24 h after irradiation. At 14 days after irradiation, both wild-type and ICAM-1(-/-) mice had an upregulation of VCAM-1, expression, and VCAM-1 immunoneutralization, but not ICAM-1 immunoneutralization, significantly reduced leukocyte adhesion. In ICAM-1(-/-) mice, regeneration of the intestinal epithelium was enhanced relative to wild-type mice. ICAM-1 plays a key role in leukocyte recruitment at early time points after abdominal irradiation, whereas VCAM-1 is the main molecular determinant of leukocyte recruitment at late time points.


Intraoperative single fraction high-dose-rate brachytherapy for head and neck cancers.
To report on the use of single fraction high-dose-rate brachytherapy in delivering localized intraoperative radiation therapy to sites in the head and neck region inaccessible to intraoperative electron beam radiotherapy (IOERT). After maximal surgical resection, 7.5-20 Gy intraoperative high-dose-rate brachytherapy (IOHDR) was delivered to 65 patients using custom-made surface applicators. The 1-, 3-, and 5-year local control rates for the entire group were 77%, 69%, and 59%, respectively. The 1-, 3-, and 5-year overall survival rates were 83%, 63%, and 42%, respectively, with a median overall survival of 50 months. There were no major intraoperative or postoperative complications. IOHDR can be used to treat selected locally advanced head and neck tumors arising at sites inaccessible to IOERT or at institutions not using IOERT. A prospective multi-institutional study with a larger number of patients treated with IOHDR is needed to firmly establish the efficacy of IOHDR in this population group.


Concomitant tension-free vaginal tape for urinary incontinence during laparoscopic hysterectomy.
To evaluate the effectiveness and safety of placing tension-free vaginal tape (TVT) during a laparoscopically assisted vaginal hysterectomy (LAVH) in women with stress urinary incontinence and coexistent benign gynaecological disease. Retrospective clinical study (Canadian Task Force classification II-2). Thirty patients diagnosed with genuine stress incontinence and benign gynaecological disease were studied. All the patients underwent LAVH and concomitant TVT procedure. There was no significant difference in urodynamic parameters before and after surgery. All patients were followed postoperatively for a mean duration of 24.6 +/- 11.5 months (range 12-40). The cure rate of stress urinary incontinence was 96.7%. Concomitant placement of tension-free vaginal tape during a laparoscopically assisted vaginal hysterectomy proved to be an efficacious and safe procedure for women with benign gynaecological disease and coexistent stress urinary incontinence.


Childhood maltreatment compromises resilience against occupational trauma exposure: A retrospective study among emergency medical service personnel.
Childhood maltreatment (CM) compromises resilience against stress and trauma throughout life. Therefore, it could present a major risk factor for the health of frequently trauma-exposed professionals such as emergency medical service (EMS) personnel. We investigated, whether EMS personnel's history of CM increased their risk for mental and physical stress symptoms after occupational trauma exposure. Data from 103 German EMS personnel (age: Mdn±QD = 26.00 ± 8.50 years) were collected as part of a cross-sectional survey distributed among employees of the regional German Red Cross EMS division (response rate 46.6%). The sample corresponded well to the division's entire staff in terms of socio-anagraphic characteristics. CM and occupational trauma exposure as well as posttraumatic, depressive, and somatic symptoms were assessed with self-report questionnaires. Moderation analyses indicated stronger positive associations between occupational trauma exposure and the severity of posttraumatic (β = .30, p < .001), depressive (β = .20, p = .026), and somatic symptoms (β = .18, p = .059) among EMS personnel who reported a higher exposure to CM. Our study provides initial evidence that CM could increase the EMS personnel's vulnerability to the detrimental consequences of critical incidents on duty. Future research is needed (i) to replicate and generalize our observation on various trauma-exposed professions as well as (ii) to develop preventive measures for targeting the mediating and protective factors which influence the relationship between CM and the negative consequences of occupational trauma exposure.


Synthesis of a terphenyl substituted 4-aza-2,3-didehydropodophyllotoxin analogues as inhibitors of tubulin polymerization and apoptosis inducers.
A series of terphenyl based 4-aza-2,3-didehydropodophyllotoxin conjugates (8a-r) were synthesized by a straightforward one-step multicomponent synthesis that demonstrated anticancer activity against five human cancer cell lines (lung, colon, renal, prostate and cervical). All the tested compounds showed potent anticancer activity with IC50 values ranging from 0.87 to 16.59 μM. Among them compounds 8n and 8p showed significant anticancer activity in lung cancer cells with IC50 values 0.91 and 0.87 μM, respectively. Flow cytometric analysis revealed that these compounds induced cell cycle arrest in G2/M phase in A549 cell line leading to caspase-3 dependent apoptotic cell death. The tubulin polymerization assay and immunofluorescence analysis showed that these compounds effectively inhibit microtubule assembly at both molecular and cellular levels in A549 cells. Further, Hoechst staining, DNA fragmentation analysis also suggested that these compounds induced cell death by apoptosis. Overall, the current study demonstrated that the synthesis of terphenyl based 4-aza-2,3-didehydropodophyllotoxin conjugates as promising anticancer agents with G2/M cell cycle arrest and apoptotic-inducing activities via targeting tubulin.


Cationic Polyelectrolytes with Alkylsulfonate Counterions as a Cathode Interface Layer for High-Performance Polymer Solar Cells.
Three cationic polyelectrolytes polyethyleneimine ethoxylate (PEIE)-1,4-butanediol dimethylsulfonate (MSB), PEIE-1,4-butanediol diethylsulfonate (ESB), and PEIE-1,4-butanediol dibenzylsulfonate (BSB), containing methylsulfonate, ethylsulfonate, and benzylsulfonate, respectively, were prepared for cathode interface layers (CILs) via a one-step reaction with 1,4-butanediol dialkylsulfonate and PEIE as the reactants. The results indicate that PEIE-MSB and PEIE-ESB with smaller counterions possess more efficient electron extraction, higher electron mobilities, and better photovoltaic performance than PEIE-BSB with larger counterions. The PTB7-Th:PC71BM-based single junction bulk heterojunction polymer solar cells (PSCs) with PEIE-ESB as the CIL showed power conversion efficiencies (PCEs) of 10.44 and 9.23% under the thickness conditions of 8 and 30 nm, respectively. The PM6:Y6-based PSCs displayed a high PCE of 15.69%. The study provides not only new high-performance CILs but also a new strategy to construct light-soaking-free PSCs via tuning alkylsulfonate counterions.


Cost and outcome analysis.
The analysis of cost issues has become increasingly important in all fields of medicine. Understanding these economic analyses can make providers more cognizant of the ultimate health, economic, and social outcomes of their treatment decisions. The methodology of cost studies and the surgical costs of treatment of intracranial metastatic tumors warrant review. Costs of surgical and radiosurgical treatment are in the range of that for the care of other serious illnesses, but comparison of the available options is still sensitive to assumptions, and open to varied interpretations.


Experimental evaluation of the accuracy of skin dose calculation for a commercial treatment planning system.
This work investigates the accuracy of skin dose calculations using the Eclipse treatment planning system. Skin dose was measured using micro-MOSFETs for a range of irradiation conditions (open fields, physical wedges, dynamic wedges, different SSDs) for 6MV and 10MV beams, and compared with the mean dose calculated to a 2mm thick "skin" structure for semi-cylindrical phantoms (representative of a neck or breast). Agreement between the calculated and measured skin dose values was better than +/-20% for 95% of all measured points (both 6MV and 10MV x-ray spectra). For a fixed geometry, the TPS correctly calculated relative changes in dose, showing that minimization of skin dose in IMRT will be effective in Eclipse.


Current therapies and investigational drugs for peripheral arterial disease.
Peripheral artery disease (PAD) is associated with elevated morbidity and mortality with cardiovascular (CV) disease. The guideline recommends smoking cessation and antiplatelet/antithrombotic drugs for asymptomatic and symptomatic PAD patients. It also recommends that PAD patients with critical limb ischemia (CLI) should be considered to receive endovascular and open surgical treatment for limb salvage. Although PAD patients with CLI receive these treatments, they are sometimes unable to deliver sufficient blood flow to eliminate their symptoms. Thus specific strategies are needed to promote enough blood flow. To establish the effective method, many investigations have been performed using cell-based therapy. Endothelial progenitor cells, mononuclear cells and mesenchymal stem cells have been well investigated in clinical settings. To induce angiogenesis, vascular endothelial growth factor, fibroblast growth factor and hepatocyte growth factor (HGF) have also been transfected in PAD patients. Among them, HGF is the most promising factor because it can induce angiogenesis without the induction of vascular inflammation and increased permeability. In this review article, we summarize current treatments and investigational drugs of PAD.


Ultrastructure of two opposite types of abdominal perisympathetic organs in the heteropteran, Roscius elongatus Stål (Pyrrhocoridae). Abundant release of neurosecretory product by intraganglionic organs.
The ultrastructural study of perisympathetic organs (POs) in Roscius elongatus revealed the existence of two opposite neurohemal structures. Distal POs formed a network at the end of each of the first pro-, meso-, metathoracic, and abdominal nerves. They display a thin branched structure favoring contact between axon endings and hemolymph. The distal metathoracic POs contained two types of neurosecretory ending, and the distal abdominal POs three types. On the contrary, "subjacent" POs, strangely located laterally in the abdominal area of the ganglionic nerve mass, display a dense compact structure, containing only one type of neurosecretory ending. These characters demonstrate that the "subjacent" POs, earlier classified as transverse POs because they are symmetrically located, are in fact median POs. In transverse POs, signs of extrusion by exocytosis were observed only in one type of neurosecretory ending. In "subjacent" POs unusual pictures were found indicating abundant release by single or compound exocytosis. Such pictures prove that "subjacent" POs have a neurohemal function despite their dense structure and internal localization. Physiological implications of these opposite structures are discussed.


A biomechanical comparison of plate configuration in distal humerus fractures.
Our aim was to test the hypothesis that two plates placed parallel to each other are stronger and stiffer than plates placed perpendicular to each other for fixation of a distal humerus fracture model. We created an artificial distal humeral fracture model by osteotomizing two groups of identical epoxy resin humera. Screw and plate constructs were built to mimic osteosynthesis. In the first group, 3.5-mm reconstruction plates were placed parallel to each other along each of the medial and lateral supracondylar ridges. In the second group, 3.5-mm reconstruction plates were placed perpendicular to each other with a medial supracondylar ridge plate and a posterolateral plate. Stiffness and strength data of the two constructs were obtained by testing to failure with sagittal plane bending forces. The parallel plate group (n = 7) had a mean stiffness of 214.9 +/- 43.3 N/mm and a mean strength of 304.4 +/- 63.5 N. The perpendicular plate group (n = 8) had a mean stiffness of 138.3 +/- 44.6 N/mm and a mean strength of 214.9 +/- 43.3 N. These differences were significant (Student's t test, P < 0.05). As theoretically expected, a parallel plate configuration is significantly stronger and stiffer than a perpendicular plate configuration when subjected to sagittal bending forces in a distal humerus fracture model.


Stated and Revealed Preferences for Funding New High-Cost Cancer Drugs: A Critical Review of the Evidence from Patients, the Public and Payers.
The growing focus on patient-centred care has encouraged the inclusion of patient and public input into payer drug reimbursement decisions. Yet, little is known about patient/public priorities for funding high-cost medicines, and how they compare to payer priorities applied in public funding decisions for new cancer drugs. The aim was to identify and compare the funding preferences of cancer patients and the general public against the criteria used by payers making cancer drug funding decisions. A thorough review of the empirical, peer-reviewed English literature was conducted. Information sources were PubMed, EMBASE, MEDLINE, Web of Science, Business Source Complete, and EconLit. Eligible studies (1) assessed the cancer drug funding preferences of patients, the general public or payers, (2) had pre-defined measures of funding preference, and (3) had outcomes with attributes or measures of 'value'. The quality of included studies was evaluated using a health technology assessment-based assessment tool, followed by extraction of general study characteristics and funding preferences, which were categorized using an established WHO-based framework. Twenty-five preference studies were retrieved (11 quantitative, seven qualitative, seven mixed-methods). Most studies were published from 2005 onward, with the oldest dating back to 1997. Two studies evaluated both patient and public perspectives, giving 27 total funding perspectives (41 % payer, 33 % public, 26 % patients). Of 41 identified funding criteria, payers consider the most (35), the general public considers fewer (23), and patients consider the fewest (12). We identify four unique patient criteria: financial protection, access to medical information, autonomy in treatment decision making, and the 'value of hope'. Sixteen countries/jurisdictions were represented. Our results suggest that (1) payers prioritize efficiency (health gains per dollar), while citizens (patients and the general public) prioritize equity (equal access to cancer medicines independent of cost or effectiveness), (2) citizens prioritize few criteria relevant to payers, and (3) citizens prioritize several criteria not considered by payers. This can explain why payer and citizen priorities clash when new cancer medicines are denied public funding.


Hypoalbuminemia may predispose infants to necrotizing enterocolitis.
Numerous risk factors for necrotizing enterocolitis (NEC) including prematurity, bowel ischemia, pathogenic bacteria, and hyperosmolar feedings have been proposed. Recent studies have demonstrated feeding intolerance and bowel dysfunction in children with hypoalbuminemia. No association between hypoalbuminemia and NEC has been suggested. The records of 45 patients with NEC and complete documentation of prenatal and birth histories were reviewed. A control (CONT) group of 90 children matched for maternal age (+/- 1 year), parity, gestational age (+/- 1 week), birth weight (+/- 20 g), type of delivery, sex, race, type of initial feeding, and perinatal stress was compiled. While all other measured parameters were similar in the two groups, premorbid albumin was significantly lower in the patients who subsequently developed NEC (P less than .001). These data suggest that newborns with hypoalbuminemia may have an increased risk of developing NEC.


Mitochondrial Genome Structure of Photosynthetic Eukaryotes.
Current ideas of plant mitochondrial genome organization are presented. Data on the size and structural organization of mtDNA, gene content, and peculiarities are summarized. Special emphasis is given to characteristic features of the mitochondrial genomes of land plants and photosynthetic algae that distinguish them from the mitochondrial genomes of other eukaryotes. The data published before the end of 2014 are reviewed.


UV-A light regulation of arylalkylamine N-acetyltransferase activity in the chick pineal gland: role of cAMP and proteasomal proteolysis.
Acute exposure of dark-adapted, cultured chick pineal glands to UV-A light significantly decreased the tissue cAMP concentration and the activity of arylalkylamine N-acetyltransferase (AANAT), the penultimate and key regulatory enzyme in the melatonin biosynthetic pathway. The magnitude of these changes was dependent on the duration of UV-A exposure. The UV-A light-evoked decline in pineal AANAT activity was blocked by cAMP protagonists (forskolin and dibutyryl-cAMP) and by inhibitors of the proteasomal degradation pathway (MG-132, proteasome inhibitor I, and lactacystin). These results indicate that the chick pineal gland is directly sensitive to UV-A light. By analogy to white light, the suppressive action of UV-A radiation on AANAT activity in the chick pineal gland involves changes in the tissue cAMP level and enhanced proteasomal proteolysis.


Treatment of squamous cell carcinoma of the anterior faucial pillar-retromolar trigone.
Cancer of the anterior faucial pillar-retromolar trigone is an uncommon head and neck tumor, which has historically been shown to be associated with poor prognosis. In this retrospective study, we reviewed our experience with primary surgery followed by postoperative radiation therapy in order to determine the impact of our treatment protocols on patients' outcome. Between January 1994 and December 1998, 31 patients with histologically proven squamous cell carcinoma (SCC) of the anterior faucial pillar-retromolar trigone were treated in our department. Surgical excision of the primary lesion and ipsilateral neck dissection were performed in all patients. Reconstruction was accomplished using masseter muscle flap or tongue flap. Postoperatively, most patients (90%) received radiation therapy (51-58 Gy) to the primary side and neck. Adjuvant chemotherapy was offered if histologic signs of aggressive behavior were identified. Four out of 31 patients were initially seen at stage I or II and 27 patients at stage III or IV of the disease. Metastatic disease was demonstrated in 78% of ipsilateral neck nodes. Occult metastases were found in 64% of clinically N0 necks. The 3-year loco-regional recurrence rates were 44.8%. SCC of retromolar trigone is considered as an aggressive and insidious tumor. The reconstruction of the deficit of the anterior faucial pillar-retromolar area with masseter muscle flap is a reliable, safe and absolutely functional method.


Phacolytic glaucoma and lens-induced uveitis.
The pathogenesis of lens-induced uveitis and phacolytic glaucoma is still not fully understood. The authors report a case of a 62-year-old white female, with bilateral lens dislocation into the vitreous, who presented clinical and pathological features of phacolytic glaucoma in the left eye. The ultrastructural study of aqueous and vitreous aspirates showed lenticular fragments and macrophages with lipofuscin granules and phagocytic vacuoles containing lens proteins. Immunocytochemistry revealed foamy macrophages immunoreactive for CD68 and HLA-DR. One year later the right eye disclosed a mild anterior granulomatous uveitis with corneal mutton-fat keratic precipitates that remained unchanged in the course of sixteen months follow-up without further treatment. These findings corroborate the possibility that, besides their mechanical and inflammatory roles in the impairment of the outflow system of the (exciting) left eye, phacolytic macrophages might also have been involved in the afferent phase of the mild chronic uveitis of the (fellow) right eye.


In vitro prostaglandin biosynthesis in human pregnant uterus from arachidonic acid.
Formation of prostaglandins (F2alpha, E2 and D2) in the pregnant human uterus microsomes was studied using 14C-labeled arachidonic acid. Sample of uterine pieces were removed from the lower uterine segment at the time of Caesarean section. The prostaglandin synthesis in the microsomal fraction was characterized in terms of cofactors, substrate concentration and incubation time requirements.


Allosteric inhibitors of HMG-CoA reductase, the key enzyme involved in cholesterol biosynthesis.
The corrole-based catalytic antioxidant reduced the cholesterol biosynthesis ability of macrophages, harvested from mice treated with it. and a non-redox active analogue of it affect the committed step of the biosynthetic pathway--the HMG-CoA reductase catalysed reaction--by acting as allosteric inhibitors of this key enzyme.


Hydrogel platform capable of molecularly resolved pulling on cells for mechanotransduction.
The active forces exerted from the extracellular matrix (ECM) to mechanoreceptors have crucial impact on many cell functions and disease development. However, our understanding of the underlying mechanisms is held back due to the lack of ECM mimicking platform able to apply molecularly resolved forces to cells. Herein, we present novel hydrogel platform capable of generate pN range forces to specific cellular receptors, at molecular scale. This capability was achieved through near-infrared (NIR) light regulated macromolecular actuators functionalized within the platform. This platform enables us to reveal cell responses to molecularly resolved forces under controlled magnitude (150-400 pN) and frequency (up to 100 Hz) on matrix with varied stiffness. We find the stiffness of the matrix has a large influence on the applied force transduction to cells. This versatile platform holds the potential for establishing correlation between receptor signaling pathways and cellular responses closer to physiological conditions.


Correction to: Microbiome definition re-visited: old concepts and new challenges.
An amendment to this paper has been published and can be accessed via the original article.


Truncus Arteriosus and Absent Ascending Aorta With Unusual Head and Neck Vessel Origins.
We describe a neonate with a unique variant of truncus arteriosus with interrupted aortic arch, an absent ascending aorta, persistent right dorsal aorta, and an unusual brachiocephalic artery pattern in which all head and neck vessels were supplied from the ductal arch-descending aorta continuum. (Level of Difficulty: Beginner.).


The environmental impact of inhalers for asthma: A green challenge and a golden opportunity.
The propellants in metered-dose inhalers (MDIs) are powerful greenhouse gases, which account for approximately 13% of the NHS's carbon footprint related to the delivery of care. Most MDI use is in salbutamol relievers in patients with poorly controlled disease. The UK lags behind Europe in this regard, with greater reliance on salbutamol MDI and correspondingly greater greenhouse gas emissions, roughly treble that of our European neighbours. There has been a broad switch towards MDIs in asthma treatment in the UK over the last 20 years to reduce financial costs, such that the treatment for two-thirds of asthma patients in the UK is dominated by salbutamol MDI. Strategies that replace overuse of reliever MDIs with regimes emphasising inhaled corticosteroids have the potential to improve asthma control alongside significant reductions in greenhouse gas emissions. Real-world evidence shows that once-daily long-acting combination dry-powder inhalers (DPIs) can improve compliance and asthma control, and reduce the carbon footprint of care. Similarly, maintenance and reliever therapy (MART), which uses combination reliever and inhaled steroids in one device (usually a DPI), can simplify therapy, improve asthma control and reduce greenhouse gas emissions. Both treatment strategies are popular with patients, most of whom would be willing to change treatment to reduce their carbon footprint. By focussing on patients who are currently using high amounts of salbutamol MDI and prioritising inhaled steroids via DPIs, there are golden opportunities to make asthma care in the UK more effective, safer and greener.


Uptake of leucine and alanine by cultured cerebral capillary endothelial cells.
Pure cultures of rat cerebral capillary endothelium have been used to study the A- and L-systems of amino acid transport. Leucine is taken up by a non-concentrative mechanism that can be saturated, and competitively inhibited by phenylalanine. Uptake is rapid, with equilibration apparent after 3-5 min (all experiments performed at 37 degrees C). The Km for transport was 83 microM +/- 26 (mean +/- S.E.M., n = 3) which is in good agreement with recent in vivo reports using unanaesthetised rats. Alanine was transported by a saturable, concentrative mechanism. Dependence on Na+-ions was demonstrated by lack of specific uptake in Na+-free buffer and reduced uptake after preincubation in ouabain--a Na+,K+-ATPase inhibitor. The Km for transport was 325 microM +/- 88 (mean +/- S.E.M., n = 3). The finding of an active A-system transporter in vitro suggests that the cells may have lost the polarity they demonstrate in vivo. The relevance of these findings to transport of nutrients and drugs across the blood-brain barrier is discussed.


Keratinocyte growth factor-2 inhibits bacterial infection with Pseudomonas aeruginosa pneumonia in a mouse model.
To determine protective effects of concurrent administration of Keratinocyte growth factor-2 (KGF-2) with Pseudomonas aeruginosa (P. aeruginosa) inoculation on the induced pneumonia. KGF-2 (5 mg/kg) was concurrently administered into the left lobe of 55 mice with P. aeruginosa PAO1 (5 × 10(6) CFU, half-lethal dose); 55 mice in the control group were concurrently administered PBS with the PAO1. We detected and analyzed: body temperature; amount of P. aeruginosa in homogenates; count of total number of nucleated cells and of mononuclear macrophages; protein concentration in bronchoalveolar lavage fluid (BALF); lung wet-to-dry weight ratio; cytokines in BALF and blood; and lung morphology. To study survival rate, concurrent administration of KGF-2 (experimental group) versus PBS (control) with a lethal dose of PAO1 (1 × 10(7) CFU was performed, and survivorship was documented for 7 days post-inoculation. The bacterial CFU in lung homogenates was significantly decreased in the KGF-2 group compared to the control group. There were significantly more mononuclear macrophages in the BALF from the KGF-2 group than from the control group (p < 0.05). KGF-2 increased the surfactant protein and GM-CSF mRNA in lung at 6 h and 72 h after inoculation. Significant reduction of lung injury scores, protein concentrations, lung wet-to-dry weight ratio, and IL-6 and TNF-α levels was noted in the KGF-2 treated rats at 72 h after inoculation (p < 0.05). The 7-day survival rate of the KGF-2 group was significantly higher than that of the control group (p < 0.05). Concurrent administration of KGF-2 facilitates the clearance of P. aeruginosa from the lungs, attenuates P. aeruginosa-induced lung injury, and extends the 7-day survival rate in mice model with P. aeruginosa pneumonia.


Total laparoscopic hysterectomy in the management of endometrial carcinoma.
To compare total laparoscopic hysterectomy (TLH) with open hysterectomy in the management of endometrial carcinoma. Retrospective chart review (Canadian Task Force classification II-3). Gynecologic cancer center. All women with endometrial carcinoma managed between January 1, 1993, and June 30, 1999. Of 403 patients reviewed, in 161 (40%) the surgical intention was laparoscopic management, in 230 (57%) the intention was open management, and in 12 (3%) it was vaginal hysterectomy. Total laparoscopic hysterectomy was successfully completed in 153 (95%) of the laparoscopic group. Mean weight of women in the laparoscopic group (80.1 kg) was greater than that in the open group (73.3 kg, p = 0.002), and included 27 patients weighing over 100 kg (maximum individual weight 170 kg). Mean operating times were 138 minutes for laparoscopy and 121 minutes for the open procedure (p = 0.002). Complications differed, with significantly more occurring in the open group (43%, 100) than in the laparoscopic group (17%, 27, p <0.00001). Mean postoperative hospital stay was significantly shorter for the laparoscopic group (4.3 days) than for the open group (8.5 days, p = 0.0001). Conclusion. TLH combined with laparoscopic surgical staging has many advantages over the open approach, especially in obese women.