The soccer goalkeeper profile: bibliographic review.
The main aim of this article was to review the existing scientific literature on the soccer goalkeeper. This article has reviewed the scientific literature related to the soccer goalkeeper as long as they offered specific information about this position on the field, including a total of 56 scientific articles. The knowledge already recollected by authors to be able to apply it on training has been divided in the following chapters: anthropometric profile, conditional and performance profile (sprint, jump, agility, strength, aerobic capacity, mobility, and specific game technique), external load profile, and injury pathological profile. The most noteworthy conclusions obtained are: 1) the higher the level of the team, the higher and heavier the goalkeepers; 2) in early ages (9-13 years) the training of goalkeepers is not well posed, since compared to the players are worse both in physical capacities and technique; 3) the aerobic capacity at long distances does not influence the performance of the goalkeeper; 4) the sprint, the jump, the agility, and the mobility are factors that determine the performance of the goalkeeper; 5) the goalkeepers are less likely to be injured than the field players, but there are certain typical injuries in the position that must be protected by a proper way of strengthening and technique.


Boosting the sonophotocatalytic performance of BiOCl by Eu doping: DFT and an experimental study.
Bismuth oxychloride (BiOCl) has a unique layered structure and uneven charge distribution, resulting in an internal electric field under polarization, which promotes the efficient separation and migration of photogenerated carriers. BiOCl could be a candidate for sonophotocatalysts. However, the low utilization of visible light limits the application of BiOCl in photocatalysts. In this study, the photocatalytic performance of rare earth element (Nd, Sm, Eu, Er and Er)-doped BiOCl was studied by density functional theory (DFT) and experimentally to screen high-performance catalysts. The band structure, density of states, and optical properties were calculated by the DFT method to predict the photocatalytic activity of rare earth-doped BiOCl. The built-in electric field formed in Eu-doped BiOCl inhibiting electron and hole recombination can be observed. Subsequently, the activity of the photocatalyst and sonophotocatalysts was evaluated. The results show that the photocatalytic and sonophotocatalytic activity of Eu-doped BiOCl is improved, which is consistent with the theoretical prediction. Combining theoretical calculations with experiments, the sonophotocatalytic activity of Eu-doped BiOCl is enhanced, mainly due to the synergistic effect of inhibiting carrier recombination, and expansion to the visible light absorption region.


Non-specific resistance to Babesia divergens in the Mongolian gerbil (Meriones unguiculatus).
Inoculation of mature gerbils with BCG gave protection to subsequent infection with B. divergens when inoculated by the intracardiac and intraperitoneal routes, the latter showing a dose dependent relationship. BCG vaccination was most effective in immature gerbils (less than 4 weeks old), which are innately resistant to B. divergens. Vaccination of gerbils with killed Propionesbacterium acne and zymosan A failed to elicit a protective response, which contrasts conspicuously with rodent babesia studies. Incubation of B. divergens-infected gerbil blood with hydrogen peroxide produced parasite inhibition only at the highest concentration and treatment of parasitized gerbils with the oxidative radical inducer, alloxan monohydrate, gave equivocal results so it is evident that, unlike Plasmodium spp., B. divergens is not significantly susceptible to the action of reactive oxygen forms.


Dietary nitrates, nitrites, and cardiovascular disease.
Dietary nitrate (NO(3)), nitrite (NO(2)), and arginine can serve as sources for production of NO(x) (a diverse group of metabolites including nitric oxide, nitrosothiols, and nitroalkenes) via ultraviolet light exposure to skin, mammalian nitrate/nitrite reductases in tissues, and nitric oxide synthase enzymes, respectively. NO(x) are responsible for the hypotensive, antiplatelet, and cytoprotective effects of dietary nitrates and nitrites. Current regulatory limits on nitrate intakes, based on concerns regarding potential risk of carcinogenicity and methemoglobinemia, are exceeded by normal daily intakes of single foods, such as soya milk and spinach, as well as by some recommended dietary patterns such as the Dietary Approaches to Stop Hypertension diet. This review includes a call for regulatory bodies to consider all available data on the beneficial physiologic roles of nitrate and nitrite in order to derive rational bases for dietary recommendations.


Fourier transform infrared microscopy of calcified turkey leg tendon.
Fourier transform infrared microscopy (FT-IRMS) was used to monitor spatial variations in the quality and quantity of the mineral phase in calcified turkey tendon. Spectral maps were generated by analysis of 50 microns x 50 microns areas within different regions of the tendon. Spectra of the transitional region, where nonmineralized matrix ends and mineralized matrix begins, revealed marked changes in the spectrally determined mineral-to-matrix ratio, whereas regions deeper into the mineralization front showed a relatively constant ratio. Since spectra of EDTA-demineralized matrix were similar to those of nonmineralized matrix, the nonmineralized regions of the tendon were used for spectral subtraction. The broad, relatively featureless contour of the mineral v1, v3 phosphate region (900-1200 cm-1) showed only subtle changes at different stages of mineralization. Second derivatives of these spectra were calculated and compared with those of synthetic, poorly crystalline hydroxyapatite (HA). The peak positions seen in second-derivative spectra of the mineral near the transitional region were within +/- 2 cm-1 of the least mature synthetic HAs whereas spectra of the mineral deeper into the mineralization front were within +/- 2 cm-1 of the most mature synthetic HAs. Spectra from cross- and longitudinal sections at equivalent positions in the tendon, and polarized FT-IRMS data were analyzed to determine the effect of mineral orientation on the parameters used to characterize the mineral. Spectra of cross- and longitudinal sections of the tendon showed no major differences in either the v1, v3 phosphate region or the amide I, II, or III components (1200-1800 cm-1). However, polarized FT-IR spectra revealed dramatic differences in both of these regions. Despite these differences, second-derivative analysis of the v1, v3 regions revealed no significant changes in the positions of the underlying bands used to characterize the environments of the phosphate ion in poorly crystalline HA. The results of this study demonstrate the power of FT-IRMS to monitor spatial variations of the mineral phase in calcified tissue. Also, the incorporation of polarized radiation provides a method capable of assessing the molecular orientation of the mineral phase relative to the collagen matrix.


Seasonal variation in cuckoldry rates in the socially monogamous cichlid fish Variabilichromis moorii.
Mating patterns in animal populations can respond to environmental conditions and consequently vary across time. To examine this variation in nature, studies must include temporal replicates from the same population. Here, we report temporal variation in genetic parentage in the socially monogamous cichlid Variabilichromis moorii from Lake Tanganyika, using samples of broods and their brood-tending parents that were collected across five field trips from the same study population. The sampled broods were either spawned during the dry season (three field trips) or during the rainy season (two trips). In all seasons, we detected substantial rates of extra-pair paternity, which were ascribed to cuckoldry by bachelor males. Paternity shares of brood-tending males were consistently higher, and the numbers of sires per brood were consistently lower, in broods that were spawned in the dry seasons compared to broods from the rainy seasons. In contrast, the strength of size-assortative pairing in our V. moorii population did not vary temporally. Seasonal fluctuations in environmental conditions, such as water turbidity, are proposed as a mechanism behind variable cuckolder pressure. Our data demonstrate the utility of long-term monitoring to improve our understanding of animal mating patterns. The online version contains supplementary material available at 10.1007/s10750-022-05042-0.


Predictors of adverse drug reactions associated with ribavirin in direct-acting antiviral therapies for chronic hepatitis C.
To identify factors associated with the development of adverse drug reactions (ADR) in ribavirin therapeutic regimens. A multicenter, prospective study was conducted in three public health hospitals in Rio de Janeiro between November 2015 and March 2018. Inclusion criteria were defined by patient follow-up at pharmaceutical consultation at the time of drug dispensing as those who used sofosbuvir in combination with simeprevir, daclatasvir, and/or ribavirin. All patients were invited to participate in the study during the first interview. Adverse drug reactions were reported according to the treatment regimen and frequency of occurrence. Statistical analysis was used to compare adverse reactions between treatments and their associated factors. A total of 405 patients were included in the study (mean age 59.6 ± 9.6 years); 61.0% were female, 88.1% were infected with genotype 1, and 65.4% were cirrhotic. The most prescribed treatment was the combination of sofosbuvir, daclatasvir, and ribavirin (55.3%). The majority of patients reported at least one ADR during treatment (83.2%), of which fatigue, anemia, and headache were the most common. Being female (OR = 1.86, [1.08-3.20]) and use of ribavirin (OR: 2.39; 95% CI [1.38-4.13]) were predictors for the development of ADR, which was also associated with development of anemia (OR: 10.28; 95% CI: [5.78-18.30]). Treatment efficacy was 98.1%. Direct-acting antiviral has been shown to be safe and effective. Therefore, use of ribavirin is questionable due to associated adverse reactions and similar efficacy to other treatments.


[Medical cooperation using IT networks--From the medical care experience of a patient with terminal amyotrophic lateral sclerosis (ALS)].
We have created an IT network with a chat feature and have provided at-home medical care to one ALS patient through hospital-home cooperation. The IT network was operated by staff involved in hospital and at-home medical care, who recorded the details of the medical care they provided in the chat server installed at the University of Fukui Hospital via cellular phones or personal computers. During the 51-day operating period of the network, information was entered 118 times; all staff could browse this information. Hospital staff supported home medical care staff by sending replies to the questions of home staff. This experience suggested that the use of the IT network could increase the level of contribution by neurology specialists in home medical care.


Flexor reflex responses triggered by imposed knee extension in chronic human spinal cord injury.
Hypersensitivity of the flexor reflex pathways to input from force-sensitive muscle afferents may contribute to the prevalence and severity of muscle spasms in patients with spinal cord injury (SCI). In this study, we triggered flexor reflexes with constant velocity knee movements in 15 subjects with SCI. Ramp and hold knee extension perturbations were imposed on one leg while the hip and ankle were held in an isometric position using an instrumented leg brace. Knee, ankle and hip torque responses and electromyograms from six muscles of the leg were recorded following controlled knee extension at four different velocities. Tests were conducted with the hip in both flexed and extended positions. During the movement into knee extension, a velocity-dependent stretch reflex, represented by a progressively increasing knee flexion torque, was observed. In addition, another type of reflex that resembled a flexor reflex (flexion of the hip and ankle) was also triggered by the imposed knee extension. The magnitude of the ankle dorsiflexion torque responses was significantly correlated to the stretch reflex torque at the knee in 9 of the 15 subjects. We concluded that stretch reflexes initiate a muscle contraction that then can contribute to a flexor reflex response, possibly through muscle group III/IV afferent pathways. These results suggest that spasticity in SCI consists of a myriad of complex reflex responses that extend beyond stretch reflexes.


Diabetes insipidus and pregnancy. Case report, incidence and review of literature.
The coexistence of diabetes insipidus (D.I.) and pregnancy is rare. Sixty-seven cases are reviewed, including one of our own. The condition tends to become worse in pregnancy, labor appears unaffected and lactation appears to lead to an improvement in D.I. Theories are discussed to account for the effect of pregnancy on D.I.


Effects of nitrogen additions on mesophyll and stomatal conductance in Manchurian ash and Mongolian oak.
The response of plant CO2 diffusion conductances (mesophyll and stomatal conductances, gm and gsc) to soil drought has been widely studied, but few studies have investigated the effects of soil nitrogen addition levels on gm and gsc. In this study, we investigated the responses of gm and gsc of Manchurian ash and Mongolian oak to four soil nitrogen addition levels (control, low nitrogen, medium nitrogen and high nitrogen) and the changes in leaf anatomy and associated enzyme activities (aquaporin (AQP) and carbonic anhydrase (CA)). Both gm and gsc increased with the soil nitrogen addition levels for both species, but then decreased under the high nitrogen addition level, which primarily resulted from the enlargements in leaf and mesophyll cell thicknesses, mesophyll surface area exposed to intercellular space per unit leaf area and stomatal opening status with soil nitrogen addition. Additionally, the improvements in leaf N content and AQP and CA activities also significantly promoted gm and gsc increases. The addition of moderate levels of soil nitrogen had notably positive effects on CO2 diffusion conductance in leaf anatomy and physiology in Manchurian ash and Mongolian oak, but these positive effects were weakened with the addition of high levels of soil nitrogen.


Intracerebral interleukin-1beta impairs response to tumor invasion: involvement of adrenal catecholamines.
Interleukin-1beta (IL-1beta) is released within the brain following stress, trauma, infection, and in specific brain disorders. This centrally acting IL-1beta has recently been shown to impair peripheral immunity. Central administration of IL-1beta suppresses natural killer (NK) cell activity impairs lung clearance of tumor cells and enhances tumor colonization. Using an in vivo model of tumor colonization (lung clearance of NK-sensitive MADB106 adenocarcinoma cells), this study examined the role of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) in mediating these effects. We demonstrate that adrenalectomy significantly attenuated the impaired lung clearance of MADB106 tumor cells induced by intracerebroventricular (i.c.v.) administration of IL-1beta (20 ng). Supplementing adrenalectomized animals with corticosterone did not reinstate the effect. The effect of IL-1beta on lung clearance was blocked by pretreatment with the beta-adrenergic antagonist, nadolol (0.5 mg/kg), but not by the alpha-antagonist phentolamine (5 mg/kg). Peripheral noradrenergic pathways are not implicated given that systemic administration of the noradrenergic neurotoxin, 6-hydroxydopamine, did not block the effect of IL-1beta. Taken together, these findings indicate that IL-1beta impairs lung clearance of MADB106 tumor cells via the actions of adrenal catecholamines, most likely epinephrine, acting at beta-adrenergic receptors in the periphery.


Change in Cobb angle of each segment of the major curve after posterior vertebral column resection (PVCR): a preliminary discussion of correction mechanisms of PVCR.
Posterior vertebral column resection (PVCR) is an effective technique for treating severe rigid spinal deformities, and no other osteotomy is capable for such an excellent corrective effects. The purpose of this study was to discuss the correction mechanisms of PVCR. Forty-six patients with severe rigid spinal deformities undergoing PVCR were retrospectively analyzed. According to a routine posteroanterior supine entire spine radiograph performed before and after surgery, the major curve at coronal plane was divided into three segments factitiously: upper segment (from the superior endplate of the upper vertebra of the major curve to the inferior endplate of the upper vertebra adjacent to the resected vertebra), middle segment (from the inferior endplate of the upper vertebra adjacent to the resected vertebra to the superior endplate of the lower vertebra of the resected vertebra), and lower segment (from the superior endplate of the lower vertebra of the resected vertebra to the inferior endplate of the lower end vertebra of the major curve). Cobb method was used to measure the curvature of the major curve and each segment. We analyzed the changes of the Cobb angle in the major curve and each segment. We also analyzed the correlation between the placement of pedicle screws and deformity correction. The Cobb angle of the major curve decreased from 110.1 ± 18.1° to 51.0 ± 17.3° (p < 0.05) after surgery (decreased by 59.1 ± 16.4°), the mean correction rate was 54.1 ± 12.2% (p < 0.05). The Cobb angle of the middle segment decreased by 28.1 ± 14.7° (p < 0.05), the contribution rate was 49.1 ± 27.3%. The upper and lower segments decreased by 15.7 ± 13.1° and 15.3 ± 12.4°, respectively (p < 0.05). There were no significant differences in the contribution rate between upper and lower segments (25.2 ± 16.6% vs. 26.3 ± 22.6%) (p > 0.05). 22 patients were instrumented with at least one pedicle screw in the adjacent upper and lower vertebras of the resected vertebra and gained a better corrective effect in comparison with the others (p < 0.05). The data also indicated that deformity correction was closely related to the numbers of the pedicle screws (r = 0.82, p < 0.05). In conclusion, the middle segment offered the highest contribution rate to the deformity correction of the major curve, but at the same time the spinal cord was angulated in this segment. So, it is dangerous to gain too much deformity correction in the middle segment. Because spine would shorten and the tension in spinal cord would decrease after vertebral column resection, a better correction effect could be gained in upper and lower segments at a low risk of spinal cord injury. But it was actually too hard for such rigid spinal deformity. It could gain a better corrective effect and stability by placing more pedicle screws at major curve, especially at the upper and lower vertebras adjacent to the resected vertebra, but sometimes it was difficult to place enough pedicle screws in severe rigid spinal deformities.


Bugs, drugs, and cancer: can the microbiome be a potential therapeutic target for cancer management?
Outnumbering our own cells over ten times, gut microbes can even be considered an additional organ. Several studies have explored the association between microbiomes and antitumor drug response. It has been reported that the presence of specific bacteria might modulate cancer progression and the efficacy of anticancer therapeutics. Bacteria-targeting intervention can provide crucial guidance for the design of next-generation antitumor drugs. Here, we review previous findings elucidating the impact of gut microbiomes on cancer treatment and the possible underlying mechanisms. In addition, we examine the role of microbiome manipulation in controlling tumor growth. Finally, we discuss concerns regarding the alteration of the microbiome composition, and the potential approaches to surpass existing limitations.


Descending necrotizing mediastinitis and thoracic cellulitis due to varicella.
A 22-year-old man with varicella had associated cervical enlargement, right upper thoracic anterior and suprascapular cellulitis, and mediastinitis. A tracheostomy, right posterolateral thoracotomy, cervicotomy, and upper thoracic fasciotomy were performed 14 h after admission, draining purulent exudates from all sites. The patient was discharged on postoperative day 22.


Percutaneous treatment of a gastrocutaneous fistula after gastrostomy tube removal.
Gastrocutaneous fistula formation is a potential complication resulting from nonsurgical gastrostomy or gastrojejunostomy tube removal. Limited success in conservative treatment has been achieved with either mechanical obstruction of the tract or pharmacologically based increase in gastric pH and improvement of gastric emptying. A case of successful conservative percutaneous treatment of a gastrocutaneous fistula with use of the sequence of initial tract de-epithelialization followed by direct tract sclerosis and mechanical obstruction is presented in this article.


Pulsed electromagnetic field treatment failure in radius non-united fracture healing.
Pulsed electromagnetic field (PEMF) treatment is a non-invasive technique which has wide use in promoting healing of delayed union and non-union of bone. According to reports in the literature, PEMF has a 'success' of about 70%, but with no clear-cut reason to explain the failures. Our tests were carried out on 11 patients with radius non-unions and delayed unions; the results suggest that PEMF failure is associated with implanted metallic plates. In our view, this can be explained because the conducting plates create a uniform bone biopotential around the fracture and thus prevent the negative polarization which stimulates callus formation. Although further controlled and randomized clinical tests are needed, our results indicate that it may be necessary to remove the plates before PEMF application.


Development of a hybrid microwave-optical thermoregulation monitor for the muscle.
This paper presents the latest development of the hybrid microwave-optical thermoregulation monitor for the muscle. It is capable of warming the muscle and measuring the subsequent blood volume changes, using a novel microwave applicator with integrated optical probes. The challenge is to measure the thermoregulation response in deep tissue while minimizing any effect from the skin layer. We have introduced a skin cooling device, an additional integrated optical Laser Doppler flow monitoring probe and a temperature sensor to measure skin blood flow and temperature, respectively. The result shows that skin cooling is essential to minimize skin flow changes during microwave warming. The hybrid probe was placed on a human thigh to measure oxy/deoxy/total haemoglobin concentration changes (ΔHbO₂/ΔHHb/ΔHbT), skin flux and temperature upon microwave warming. Without skin cooling, the skin temperature was elevated by 4 °C and both ΔHbO₂/ΔHbT and skin flux increased, showing microwave warming occurring in both the skin and muscle. With skin cooling, the skin temperature was kept relatively constant. While ΔHbO₂/ΔHbT increased, the skin flux was relatively stable, showing a preferential microwave warming in the muscle, rather than the skin.


Three-dimensional polymer coated 45S5-type bioactive glass scaffolds seeded with human mesenchymal stem cells show bone formation in vivo.
45S5-type bioactive glasses are a promising alternative to established substitutes for the treatment of bone defects. Because the three-dimensional (3D) structure of bone substitutes is crucial for bone ingrowth and formation, we evaluated the osteoinductive properties of different polymer coated 3D-45S5 bioactive glass (BG) scaffolds seeded with human mesenchymal stem cells (hMSC) in vivo. BG scaffolds coated with gelatin, cross-linked gelatin, and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) were seeded with hMSC prior to implantation into severe combined immunodeficiency mice. Newly formed bone was evaluated with histomorphometry and micro-computed tomography. Bone formation was detectable in all groups, whereas the gelatin-coated BG scaffolds showed the best results and should be considered in further studies.


Rates of topoisomerase II-alpha and HER-2 gene amplification and expression in epithelial ovarian carcinoma.
Topoisomerase II-alpha (T2a) is being actively investigated as a potential predictive marker of response to anthracyclines in breast cancer (BC). Although the role of T2a inhibitors as upfront and salvage treatment for epithelial ovarian carcinoma (EOC) remains unclear, we speculated that a small subgroup of ovarian cancer patients could derive a selective benefit from these agents. In this study, we investigated the actual rates of T2a and HER-2 amplification and overexpression by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC), respectively. Seventy-three samples of chemotherapy-naive patients with EOC were selected from our archives. FIGO stage and histology were available for most patients. Based on arbitrary cut-offs of > or =1.5 and > or =2 (ratio copies/centromere17), amplification rates for HER-2 were 15/64 (23.4%) and 8/64 (12.5%) versus 16/64 (25%) and 5/64 (7.8%) for T2a. We found only 3/72 (4.2%) cases of HER-2 overexpression (3+) versus 15/70 (21.4%) for T2a (staining of >10% of the cells). There was a modest correlation between T2a amplification and overexpression (P=0.01) and a strong correlation between T2a and HER-2 amplification when these markers were analysed as continuous variables (P<0.001). T2a amplification significantly correlated with advanced FIGO stage (P=0.02). The assessment of HER-2 and T2a amplification and overexpression by FISH and IHC, respectively, is feasible in EOC. These tests can be used for large-scale evaluation of the potential predictive and prognostic value of these markers in the future. Further studies with a special focus on T2a are needed to determine the best cut-offs for potential clinical use in the future.


Interactions between the predacious fungus Arthrobotrys oligospora and third-stage larvae of a series of animal-parasitic nematodes.
Interactions between the predacious hyphomycete Arthrobotrys oligospora and third-stage larvae of nine animal-parasitic nematodes were tested in vitro. The trap-inducing capabilities of the ruminant trichostrongylus Cooperia oncophora, C. curticei, Haemonchus contortus and Ostertagia ostertagi and of equine cyathostomes were almost comparable to those of free-living soil nematodes, and significantly higher than those of the porcine Oesophagostomum dentatum and Oe. quadrispinulatum and of the murine Nematospiroides dubius. The trap-forming potential of Dictyocaulus viviparus was poor. All animal-parasitic nematodes were rapidly captured when fungal traps had been pre-induced in high numbers. The possible influence of predacious fungi on animal-parasitic nematode populations under natural conditions in the field is discussed.


Bacterial cellulose membranes as drug delivery systems: an in vivo skin compatibility study.
Bacterial cellulose (BC) is a highly pure form of cellulose, produced in the form of a swollen membrane by several bacteria that demonstrated to be able to modulate the skin release of model drugs. In the present study, the skin irritation potential of BC was evaluated in human subjects. BC membranes with and without glycerin (acting as plasticizer) were tested. No significant differences were observed for transepidermal water loss (TEWL) measurements in comparison with negative control, 2 and 24 h after patch removal, which is an indicator of an absence of barrier disruption. Similar results were found for erythema. Clinical scores were zero at both times for all volunteers, with the exception of five volunteers that exhibited weak reactions. BC with glycerin provided a skin moisturizing effect statistically higher than the negative control (p=0.044), which was not observed for BC alone. The good skin tolerance found after a single application under occlusion reinforces the putative interest of BC membranes as supports for drug topical delivery. Besides modifying the mechanical properties, the inclusion of glycerin results in a skin moisturizing effect which could be clinically relevant for the treatment for skin diseases characterized by dryness, such as psoriasis and atopic dermatitis.


Complexities of foot architecture as a base of support.
The human foot is a unique structure in the animal kingdom, as it is capable of supporting sustained bipedal gait. The foot facilitates upright walking in several ways: 1) load bearing, 2) leverage, 3) shock absorption, 4) balance, and 5) protection. In this article, we discuss the specialized architecture that enables the foot to accomplish these functions.


Integration of high-resolution array comparative genomic hybridization analysis of chromosome 16q with expression array data refines common regions of loss at 16q23-qter and identifies underlying candidate tumor suppressor genes in prostate cancer.
We have constructed a high-resolution genomic microarray of human chromosome 16q, and used it for comparative genomic hybridization analysis of 16 prostate tumors. We demarcated 10 regions of genomic loss between 16q23.1 and 16qter that occurred in five or more samples. Mining expression array data from four independent studies allowed us to identify 11 genes that were frequently underexpressed in prostate cancer and that co-localized with a region of genomic loss. Quantitative expression analyses of these genes in matched tumor and benign tissue from 13 patients showed that six of these 11 (WWOX, WFDC1, MAF, FOXF1, MVD and the predicted novel transcript Q9H0B8 (NM_031476)) had significant and consistent downregulation in the tumors relative to normal prostate tissue expression making them candidate tumor suppressor genes.


Phy meets ERFs to regulate seed germination.
The complex process of seed germination is impacted heavily by environmental cues, such as light, mediated via photosensory systems and phytochromes. This pathway was discovered a long time ago, but the underlying molecular mechanisms are not fully understood. Li et al. recently showed how ETHYLENE RESPONSE FACTORs (ERFs) modulate phytochrome-mediated regulation of germination.


Autophagy negatively regulates pro-osteogenic activity in human aortic valve interstitial cells.
Autophagy is a physiological process that plays an important role in maintaining cellular functions. When aortic valve interstitial cells (AVICs) are stimulated with inflammatory or mechanical stress, one response is elevated pro-osteogenic activity. We hypothesized that autophagy is important in the prevention or regulation of this pro-osteogenic activity in AVICs. AVICs were isolated. Autophagy activity was examined and its role in AVIC's pro-osteogenic activity was determined using chemical inhibitors and genetic techniques. The pro-osteogenic biomarker bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP) were analyzed by immunoblotting and calcium deposition assay. Human AVICs from normal aortic valve donors displayed significantly higher autophagic activity than those from calcified aortic valve donors as indicated by lower protein levels of light chain 3-II. Suppression of autophagy by 3-methyladenine, bafilomycin, or knockdown of Atg7 gene induced the expression of BMP-2 and ALP, increased ALP activity, and calcium deposit formation in normal AVICs. Conversely, upregulation of autophagy with rapamycin or overexpression of Atg7 gene decreased the levels of BMP-2 and ALP in diseased AVICs. Our data showed that autophagy negatively regulates the pro-osteogenic activity in human AVICs, suggesting that upregulation of autophagy may prevent the progression of calcific aortic valve disease.


Establishing maximal medical improvement following aseptic revision of shoulder arthroplasty.
Shoulder arthroplasty surgery volume continues to increase yearly. As the prevalence of shoulder replacement continues to rise, there will be a growing number of revision surgeries performed for a variety of indications. Understanding patient outcomes and recovery time following these procedures is critical, particularly as it relates to revision surgery, which generally has worse outcomes and longevity than primary arthroplasty. The point at which the peak of potential improvement is reached can be defined as the point of maximal medical improvement (MMI). The timing to MMI has previously been reported in the literature following both primary anatomic and reverse total shoulder arthroplasty. However, to our knowledge, timing to MMI following revision shoulder arthroplasty has not been defined. The purpose of the present study, therefore, is to establish the time to MMI following aseptic revision shoulder arthroplasty using validated patient-reported outcome measures. A retrospective cohort study was conducted following patients who underwent aseptic revision shoulder arthroplasty over a defined 3-year period. Multiple fellowship-trained shoulder and elbow surgeons from a single institution performed all operations. Those with at least 24 months of follow-up and multiple time points of postoperative patient-reported outcome scores were included in the analysis. American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores and Single Assessment Numeric Evaluation (SANE) scores were prospectively recorded and followed over time. Exclusion criteria included revision surgeries done for infection, staged procedures following infection, and revision for periprosthetic fracture. Twenty-two patients met inclusion criteria. The mean preoperative ASES and SANE scores were 41.8 and 30.5, respectively. There was a trend toward improvement in both the ASES and SANE scores through the 6-9-month postoperative follow-up point, at which point clinically significant improvement was achieved, with mean values of, respectively, 76.9 and 81.2. No further improvement was achieved 9 months after surgery, although scores were generally maintained through an average final follow-up of 30 months, with final ASES and SANE scores of 70.1 and 67.8, respectively. Following aseptic revision shoulder arthroplasty, clinically significant improvements in patient-reported outcome scores are seen up to 9 months postoperatively, the point at which MMI is achieved. These findings serve to guide clinicians in counseling patients regarding their expected postoperative recovery following revision shoulder arthroplasty.


Zinc-induced upregulation of metallothionein (MT)-2A is predicted by gene expression of zinc transporters in healthy adults.
The usefulness of zinc transporter and metallothionein (MT) gene expressions to detect changes in zinc intake remains unclear. This pilot study aimed to determine the effects of zinc supplementation on zinc transporter and MT gene expressions in humans. Healthy adults (n = 39) were randomised to zinc treatment (ZT), receiving 22 mg Zn/day (n = 19), or no treatment (NT) (n = 20). Blood samples were collected on Days 0, 2, 7, 14, and 21. Plasma zinc and serum C-reactive protein concentrations were analysed. Gene expression of zinc transporters and MT in peripheral blood mononuclear cells was analysed using real-time PCR. Using repeated-measures ANOVA, MT-2A gene expression and fold change were found to be higher in the ZT group (P = 0.025 and P = 0.016, respectively) compared to the NT group, specifically at Day 2 (40 ± 18 % increase from baseline, P = 0.011), despite no significant increase in plasma zinc concentration. In a multiple regression model exploring the changes in gene expressions between Days 0 and 21, the change in MT-2A gene expression was correlated with changes in all zinc transporter expressions (r (2) = 0.54, P = 0.029); the change in ZIP1 expression emerged as a univariate predictor (P = 0.003). Dietary zinc intake was predictive of zinc transporter and MT expressions (P = 0.030). Physical activity level was positively correlated with baseline ZIP7 expression (r = 0.36, P = 0.029). The present study shows that MT-2A expression is related to changing expression of zinc transporter genes, specifically ZIP1, in response to zinc supplementation. The current report adds to our understanding of MT in the coordinated nature of cellular zinc homeostasis.


Cranial findings detected by second-trimester ultrasound in fetuses with myelomeningocele: a systematic review.
Abnormal intracranial findings are often detected at mid-trimester ultrasound (US) in fetuses with myelomeningocele (MMC). It is unclear whether these findings constitute a spectrum of the disease or are an independent finding, which should contraindicate fetal surgery. To ascertain the spectrum and frequency of US-detected cranial findings in fetuses with MMC. MEDLINE, Embase, Web of Science and CENTRAL were searched from January 2000 to June 2020. Study reporting incidence of cranial US findings in consecutive cases of second-trimester fetuses with MMC. Publication quality was assessed by Newcastle-Ottawa Scale (NOS) and modified NOS. Meta-analysis could not be performed as a result of high clinical diversity and study heterogeneity. Fourteen cranial US findings were reported in 15 studies. Findings in classic Chiari II malformation (CIIM) spectrum included posterior fossa funnelling (96%), small transcerebellar diameter (82-96%), 'banana' sign (50-100%), beaked tectum (65%) and 'lemon' sign (53-100%). Additional cranial findings were small biparietal diameter (BPD) and head circumference (HC) (<5th centile; 53 and 71%, respectively), ventriculomegaly (45-89%), abnormal pointed shape of the occipital horn (77-78%), thinning of the posterior cerebrum, perinodular heterotopia (11%), abnormal gyration (3%), corpus callosum disorders (60%) and midline interhemispheric cyst (42%). We identified 14 cranial findings by second-trimester US in fetuses with MMC. The relatively high incidence of these findings and their unclear prognostic significance might not contraindicate fetal surgery in the case of normal fetal genetic testing. Some cranial findings may independently affect postnatal outcome, however. Long-term detailed follow-up is required to investigate this. A high rate of cranial abnormalities found on second-trimester ultrasound in fetuses with myelomeningocele.


Dual-crosslinked in-situ forming alginate/silk fibroin hydrogel with potential for bone tissue engineering.
This study aimed to improve the mechanical and biological properties of alginate-based hydrogels. For this purpose, in-situ forming hydrogels were prepared by dual crosslinking of Alginate (Alg)/Oxidized Alginate (OAlg)/Silk Fibroin (SF) through simultaneous ionic gelation using CaCO3-GDL and Schiff-base reaction. The resulting hydrogels were characterized by FTIR, SEM, compressive modulus, and rheological tests. Compared to the physically-crosslinked alginate hydrogel, the compressive modulus of dual-crosslinked Alg/OAlg/SF hydrogel increased from 28 to 67 kPa, due to the covalent imine bond formation. Then, MTT and DAPI staining assays were performed to demonstrate the biocompatibility of hydrogel. Furthermore, the differentiation potential of bone marrow mesenchymal stem cells encapsulated in hydrogel scaffolds to bone tissue was tested by ALP activity, Alizarin Red staining, and real-time PCR. The overall results showed the potential of Alginate/Oxidized Alginate/Silk Fibroin hydrogel scaffold for bone tissue engineering applications.


[Refusal of information from a legal and medical viewpoint].
Actual or implied refusal by the patient to accept an explanation of his illness is discussed with respect to its legal admissibility and the legal uncertainties for the attending physician. Refusal by the patient to accept information does not absolutely release the doctor from providing an explanation but only from that part which exceeds what is medically appropriate.


Dose-related effects of cycloheximide on delayed neuronal death in the gerbil hippocampus after bilateral transitory forebrain ischemia.
Degeneration of dendrites followed by punctate chromatin condensation in the CA1 area of the hippocampus is a characteristic of delayed neuronal death following bilateral forebrain ischemia. The effects of the protein synthesis inhibitor cycloheximide on delayed neuronal death following 20 min of bilateral forebrain ischemia were examined in the gerbil hippocampus at the 4th day of reperfusion. Low doses of cycloheximide beginning 10 min after ischemia (1.0 microgram/g body weight in saline followed by 1.0 microgram/g every 24 h) reduced the number of dying cells in the CA1 area, whereas high doses (2.0 micrograms/g, followed by 1.0 microgram/g every 12 h) increased the number of dying cells. No effects were seen when a single dose of cycloheximide was injected 1 h before ischemia. These results indicate that the effects of cycloheximide are dose-dependent, low doses reduce, high doses increase cell death. These findings also indirectly suggest that protein synthesis may play a role in the extent of delayed neuronal death. Some involved proteins could be heat shock proteins, which are induced after ischemia and had been correlated with increased resistance to injury. However, changes of heat shock immunoreactivity in the postischemic hippocampus were not seen in the present study following cycloheximide injection.


Hyperalgesia to heat after intradermal injection of capsaicin.
Capsaicin injected intradermally into the human forearm lowered the pain threshold for heat at the injection site. Both the magnitude and duration of hyperalgesia were dose dependent over the range of 0.1-100 micrograms, given in a constant volume of 10 microliter. Thus, capsaicin may be a useful tool in studies of the neural mechanisms of hyperalgesia.


A glassy carbon electrode modified with a nanocomposite prepared from Pd/Al layered double hydroxide and carboxymethyl cellulose for voltammetric sensing of hydrogen peroxide.
A Pd/Al layered double hydroxide/carboxymethyl cellulose nanocomposite (CMC@Pd/Al-LDH) was fabricated using carboxymethyl cellulose as a green substrate via co-precipitation method. The synthesized nanocomposite was characterized using different methods such as scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray powder diffraction, transmission electron microscopy, and electrochemical techniques. A glassy carbon electrode (GCE) was then modified with the suspended composite to obtain an electrochemical sensor for hydrogen peroxide (H2O2). The voltammetric (cathodic) current of the modified GCE was measured at -380 mV (vs. Ag/AgCl), at the scan rate of 50 mV.s-1. Results show a linear dynamic range of 1 to 120 μM, and a 0.3 µM limit of detection (at S/N = 3). Intraday and interday relative standard deviations are in the ranges of 4.9-5.4% and 6.8-7.3%, respectively. The sensor was applied for the determination of H2O2 in basil extracts, milk, and spiked river water samples. The recoveries are between 96.60 and 102.30%. Graphical abstractA Pd/Al layered double hydroxide/carboxymethyl cellulose nanocomposite (CMC@Pd/Al-LDH) was fabricated via co-precipitation method and was characterized using scanning electron microscopy, Energy-dispersive X-ray spectroscopy, X-ray powder diffraction, transmission electron microscopy and electrochemical techniques. CMC@Pd/Al-LDH was used to fabricate H2O2 electrochemical sensor.


Saccharide alterations in rat kidney associated with malignant transformation by injection of dimethylnitrosamine.
Renal tumours were induced in dietary-primed rats by injection of dimethylnitrosamine. Control and tumour tissue was excised at varying periods and maintained in short-term organ culture in the presence of 3H- or 14C-fucose. The plasma membranes were then isolated, and the isotopic profiles of normal kidney and renal tumour membrane proteins were established, using polyacrylamide-gel electrophoresis in dodecyl sulphate. Several fucose-containing glycoproteins of the plasma membranes were found to alter upon neoplastic transformation: 4 increased and 3 decreased. The probable identity of 2 of these proteins is indicated: alpha-foetoprotein is one of the glycoproteins which increased, whereas neutral endopeptidase decreased in the tumour membranes. Fluorescein-labelled lectin binding by the kidney tissue was also found to alter upon transformation. The most marked changes were an increase in sialic acid (neuraminidase-sensitive) and galactosamine (Ricinus communis agglutinin Type I) in the nuclei of some neoplastic cells and some hyperplastic-tubule cells.


A risk score to predict ischemic lesions after protected carotid artery stenting.
The morphological characteristics of atherosclerotic plaques are considered to determine their cerebral 'embolic potential'. However, these are seldom considered during therapeutic decision-making. Assessment and quantification of embolic potential by employing power-M-mode (PMD) transcranial Doppler (TCD) to strengthen risk scoring has been discussed. PMD-TCD is a reliable technique for monitoring of microembolic signals in intracranial arteries and can help in estimating the 'embolic potential' of carotid plaques. In addition to the diffusion-weighted imaging, assessment of neuro-cognitive functions may provide a better assessment of the safety of carotid interventions. The proposed 'risk scoring' system can be further improved by incorporating the cerebral 'embolic potential' by PMD-TCD while cognitive assessments may be used for a more reliable evaluation of the safety of various carotid interventions.


Non-random features of loop-size chromatin fragmentation.
Upon isolation of DNA from normal eukaryotic cells by standard methods involving extensive proteolytic treatment, a rather homogeneous population of loop-size, double-stranded DNA fragments is regularly obtained. These DNA molecules can be efficiently end-labeled by the DNA polymerase I Klenow fragment, as well as by a 3'- to -5'-exonuclease-free Klenow enzyme, but not by terminal transferase (TdT) unless the ends have been filled up by Klenow, suggesting that dominantly 5' protruding termini are generated upon fragmentation. The filled-up termini were used for cloning the distal parts of the approximately 50 kb fragments. BLAST analysis of the sequence of several clones allowed us to determine the sequence of the non-cloned side of the breakpoints. Comparison of 25, 600 bp-long breakpoint sequences demonstrated prevalence of repetitive elements. Consensus motives characteristic of the breakpoint sequences have been identified. Several sequences exhibit peculiar computed conformational characteristics, with sharp transition or center of symmetry located exactly at the breakpoint. Our data collectively suggest that chromatin fragmentation involves nucleolytic cleavages at fragile/hypersensitive sites delimiting loop-size fragments in a non-random manner. Interestingly, the sequence characteristics of the breakpoints are reminiscent of certain breakpoint cluster regions frequently subject to gene rearrangements.


Structure and antigenicity of divergent Henipavirus fusion glycoproteins.
In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and both are divergent from the bat-borne HNV members, Nipah (NiV) and Hendra (HeV) viruses. The spillover of LayV is the first instance of a HNV zoonosis to humans outside of NiV and HeV, highlighting the continuing threat this genus poses to human health. In this work, we determine the prefusion structures of MojV and LayV F proteins via cryogenic electron microscopy to 2.66 and 3.37 Å, respectively. We show that despite sequence divergence from NiV, the F proteins adopt an overall similar structure but are antigenically distinct as they do not react to known antibodies or sera. Glycoproteomic analysis revealed that while LayV F is less glycosylated than NiV F, it contains a glycan that shields a site of vulnerability previously identified for NiV. These findings explain the distinct antigenic profile of LayV and MojV F, despite the extent to which they are otherwise structurally similar to NiV. Our results carry implications for broad-spectrum HNV vaccines and therapeutics, and indicate an antigenic, yet not structural, divergence from prototypical HNVs.


Endoscopic Submucosal Dissection of a Giant Esophageal Liposarcoma.
We report a rare case of esophageal highly differentiated liposarcoma that was safely removed by endoscopic submucosal dissection.


Mapping of FSHR agonists and antagonists binding sites to identify potential peptidomimetic modulators.
Owing to the critical role of follicle stimulating hormone receptor (FSHR) signaling in human reproduction, FSHR has been widely explored for development of fertility regulators. Using high-throughput screening approaches, several low molecular weight (LMW) compounds that can modulate FSHR activity have been identified. However, the information about the binding sites of these molecules on FSHR is not known. In the present study, we extracted the structural and functional information of 161 experimentally validated LMW FSHR modulators available in PubMed records. The potential FSHR binding sites for these modulators were identified through molecular docking experiments. The binding sites were further mapped to the agonist or antagonist activity reported for these molecules in literature. MD simulations were performed to evaluate the effect of ligand binding on conformational changes in the receptor, specifically the transmembrane domain. A peptidomimetic library was screened using these binding sites. Six peptidomimetics that interacted with the residues of transmembrane domain and extracellular loops were evaluated for binding activity using in vitro cAMP assay. Two of the six peptidomimetics exhibited positive allosteric modulatory activity and four peptidomimetics exhibited negative allosteric modulatory activity. All six peptidomimetics interacted with Asp521 of hFSHR(TMD). Several of the experimentally known LMW FSHR modulators also participated in H-bond interactions with Asp521, suggesting its important role in FSHR modulatory activity.


Induction of apoptosis by synthetic ceramide analogues in the human keratinocyte cell line HaCaT.
In contrast to extracellular, long chain ceramides which comprise a structural component of the epidermal water barrier, intracellular ceramides originating from sphingomyelin hydrolysis have been shown to inhibit proliferation and to induce apoptosis in different cell populations. To further elucidate the possible role of intracellular ceramides in human epidermis, two new cell-permeable ceramide analogues, N-thioacetylsphingosine (C2-Cer=S) and 4-dodecanoylamino-decan-5-ol (FS-5), were synthesized and tested for their ability to suppress cell growth and to induce apoptosis in immortalized human keratinocytes. It was shown that the well-investigated ceramide analogue N-acetylsphingosine (C2-Cer=O), as well as the new compound C2-Cer=S inhibited proliferation of HaCaT cells with half-inhibitory concentrations (IC50) of 20 microg/ml and 10 microg/ml, respectively, whereas FS-5 has been potent with an IC50>40 microg/ml. Overall, all three ceramide analogues induced apoptosis in HaCaT cells as assessed by DNA-fragmentation using ELISA technique and in situ nick end labelling, thereby confirming the importance of ceramide signalling in keratinocytes.


Microsatellite instability in human testicular germ cell tumours.
DNA samples obtained from 29 testicular germ cell tumours have been screened for instability at nine different microsatellite sequences consisting of dinucleotide, trinucleotide and tetranucleotide loci. Overall, in tumours from six (21%) patients we found abnormalities in at least one of the loci examined. Mutation was most frequently found in tetranucleotide and trinucleotide repeats with only a low proportion of alterations in dinucleotide repeats. This pattern of instability is distinct from that reported in colorectal cancer and other cancers that have a high level of alterations in dinucleotide repeats.


Comparison of two retropubic tension-free vaginal tape procedures in women with stress urinary incontinence: a randomized controlled multicenter trial.
Midurethral slings are a well-established treatment option in women suffering stress urinary incontinence. Various different products and methods are used, therefore, the aim of our study was to compare two inside-out retropubic slings (TVT exact® vs. RetroArc®) inserted in two different ways regarding perioperative and mid-term outcomes. In this prospective randomized controlled non-inferiority multicentre trial, primary endpoint was postoperative cure rate, both objective (negative cough test) and subjective (absence of leakage during physical activity using the UDI-6 questionnaire). Secondary endpoints were patients' satisfaction (Likert scale; ICIQ-UI-SF questionnaires). In addition, intra-and postoperative complications were evaluated. The TVT®-group was operated with an empty bladder, a 18 CH catheter was used with a straight inserter as instructed. Patients randomized into the RetroArc®-group were operated without inserter leading to a reduced catheter size (14 CH), bladder was filled (200 ml) during the procedure. Of the 303 women, 152 were randomized to the TVT® and 151 to the RetroArc® operation. At 3 months, n = 288 (95.0%) and at 12 months n = 229 (75.6%) were assessed. In postoperative objective cure the RetroArc®-procedure was not inferior to TVT® (p = 0.144). In subjective cure, however, the TVT exact® procedure achieved significant better results (TVT® 76.1%, RetroArc® 54.3%, p = 0.002). Perioperative complications were in majority voiding difficulties and lower after the TVT exact®-procedure. Retropubic sling procedures are safe and successful to treat female stress urinary incontinence. However, different materials and techniques result in differences between outcomes also experienced surgeons should be aware of.


Immobilizing arsenic-enriched wastewater from utilization of crude antimony oxides as scorodite using a novel multivalent iron source.
Arsenic-enriched wastewater (A-EW) is a hypertoxic sewage from the utilization of crude antimony oxides in lead anode slime metallurgy. In traditional methods, the H+ accumulation inhibits the arsenic immobilization during scorodite synthesis. In this study, a novel multivalent iron source comprised of Fe(OH)3 and FeSO4·7H2O was proposed to resolve the adverse effects of pH fluctuation during immobilizing A-EW as scorodite. Various approaches, such as scanning electron microscopy and X-ray photoelectron spectroscopy, were applied to characterize the synthesized scorodite. This work was divided into two parts. In thermodynamics, HnAsO4(3-n)- (n = 1, 2, 3) and Fe(OH)n(3-n)+ (n = 0, 1, 2, 3) can feasibly coprecipitate as scorodite according to their △rGm,Tθ ranged from -111.10 kJ mol-1 to -33.53 kJ mol-1. In experimental research, A-EW was immobilized as scorodite by optimizing conditions as initial pH = 2.0, molar ratio of Fe to As = 1.2, molar ratio of Fe(II) to Fe(III) = 4:6, arsenic concentration = 40 g/L, and temperature = 95 °C. The arsenic precipitation ratio is 99.60%, and the micromorphology of synthesized scorodite presents a regular octahedron having size of 5-10 μm. The low leachability of As (0.41 mg/L) in toxicity characteristic leaching procedure (TCLP) confirmed that the prepared scorodite is nonhazardous. The solution pH is stable at 2.0 as the H+ depletion (0.5660 mol) by Fe(OH)3 dissolution and Fe2+ oxidization balanced with that (0.5657 mol) generated from As(V)-Fe(III) coprecipitation. In general, the A-EW was effectively immobilized by proposed multivalent iron source, and can be potentially applied to safely dispose other industrial effluents, such as high arsenic leachates and arsenic-bearing waste acid from nonferrous metallurgy.


Patterns of dysgraphia and the nonlexical spelling process.
This article evaluates the hypothesis that phoneme-grapheme conversion is accomplished by a passive activation device in which the selection of mapping options in the process of assembling orthography is determined by the frequency of usage of that option in the language. The spelling performance of two brain-damaged, acquired dysgraphic patients is interpreted as support for the stated hypothesis.


Hydrophilic Catalysts with High Activity and Stability in the Aqueous Polymerization of Ethylene to High-Molecular-Weight-Polyethylene.
Water-soluble synthetic transition metal catalysts have been studied extensively for many reactions, but for olefin polymerization such catalysts have been lacking. We report herein a straightforward synthesis of phosphinephenolato NiII catalysts endowed permanently with a hydrophilic sulfonate moiety bound to the chelating ligand. These catalysts' hydrophilic active sites promote aqueous ethylene polymerization with high activity (TOF up to 6.3×104 molEthylene molNi -1 h-1 ) to high molecular weight polyethylene (HDPE), with half-lives on the order of hours also at elevated temperatures. The obtained polyethylene dispersions feature narrow particle size distributions without any aggregates.


New reliable Raman collection system using the wide area illumination (WAI) scheme combined with the synchronous intensity correction standard for the analysis of pharmaceutical tablets.
A novel and reliable Raman collection system for the non-destructive analysis of pharmaceutical tablets has been proposed. The main idea was to develop and utilize the wide area illumination (WAI) scheme for Raman collection to cover a large surface area (coverage area: 28.3mm2) of solid tablet to dramatically improve the reliability in sample representation and the reproducibility of sampling due to less sensitivity of sample placement with regard to the focal plane. Simultaneously, the effective and synchronous standard configuration using isobutyric anhydride was harmonized with the WAI scheme to correct the problematic variation of Raman intensity from the change of laser power. To verify the quantitative performance of the proposed scheme, the compositional analysis of active ingredient in naproxen tablet has been performed. The average sample composition was successfully represented by using the WAI scheme compared to the conventional scheme with a much smaller illumination area. After the intensity correction using the non-overlapping peak of isobutyric anhydride standard and area normalization, a partial least squares (PLS) model was developed using an optimized spectral range and the concentrations of naproxen in tablets were accurately predicted. The prediction accuracy was not sensitive to changes in laser power or tablet position within +/-2mm. Additionally, the prediction accuracy was repeatable without systematic drift or need for re-calibration.


Promoting axon regeneration by inhibiting RNA N6-methyladenosine demethylase ALKBH5.
A key limiting factor of successful axon regeneration is the intrinsic regenerative ability in both the peripheral nervous system (PNS) and central nervous system (CNS). Previous studies have identified intrinsic regenerative ability regulators that act on gene expression in injured neurons. However, it is less known whether RNA modifications play a role in this process. Here, we systematically screened the functions of all common m6A modification-related enzymes in axon regeneration and report ALKBH5, an evolutionarily conserved RNA m6A demethylase, as a regulator of axonal regeneration in rodents. In PNS, knockdown of ALKBH5 enhanced sensory axonal regeneration, whereas overexpressing ALKBH5 impaired axonal regeneration in an m6A-dependent manner. Mechanistically, ALKBH5 increased the stability of Lpin2 mRNA and thus limited regenerative growth associated lipid metabolism in dorsal root ganglion neurons. Moreover, in CNS, knockdown of ALKBH5 enhanced the survival and axonal regeneration of retinal ganglion cells after optic nerve injury. Together, our results suggest a novel mechanism regulating axon regeneration and point ALKBH5 as a potential target for promoting axon regeneration in both PNS and CNS.


Can martial arts techniques reduce fall severity? An in vivo study of femoral loading configurations in sideways falls.
Sideways falls onto the hip are a major cause of femoral fractures in the elderly. Martial arts (MA) fall techniques decrease hip impact forces in sideways falls. The femoral fracture risk, however, also depends on the femoral loading configuration (direction and point of application of the force). The purpose of this study was to determine the effect of fall techniques, landing surface and fall height on the impact force and the loading configuration in sideways falls. Twelve experienced judokas performed sideways MA and Block ('natural') falls on a force plate, both with and without a judo mat on top. Kinematic and force data were analysed to determine the hip impact force and the loading configuration. In falls from a kneeling position, the MA technique reduced the impact force by 27%, but did not change the loading configuration. The use of the mat did not change the loading configuration. Falling from a standing changed the force direction. In all conditions, the point of application was distal and posterior to the greater trochanter, but it was less distal and more posterior in falls from standing than from kneeling position. The present decrease in hip impact force with an unchanged loading configuration indicates the potential protective effect of the MA technique on the femoral fracture risk. The change in loading configuration with an increased fall height warrant further studies to examine the effect of MA techniques on fall severity under more natural fall circumstances.


Idiopathic fibrosing mediastinitis with esophageal varices: A case report.
Fibrosing mediastinitis (FM) is a rare cause of lung fibrosis with multiple etiologies ranging from infectious to autoimmune to idiopathic. Common causes of FM include histoplasmosis and a relatively new cause of IgG4-related disease. We present a 55-year-old male with symptoms of esophageal varices, intractable hiccups, and progressive difficulty in breathing. A chest X-ray showed right lung fibrosis with pleural effusion and loss of lung volume, which was originally thought to be the sequelae of SARS-CoV-2 or metastasis, but computed tomography of the chest revealed FM. His variceal bleeding was controlled, and he was discharged home. However, treatment for FM was not pursued because the cause was not identified. Using corticosteroids may not cease the progression of the disease, and surgical options are available when symptoms persist. Idiopathic FM requires laboratory and radiological findings to exclude relevant differential diagnoses.


Sex-specific changes in the expression of kisspeptin, kisspeptin receptor, gonadotropins and gonadotropin receptors in the Senegalese sole (Solea senegalensis) during a full reproductive cycle.
Kisspeptin is thought to have a major role in the control of the onset of puberty in vertebrates. However, our current understanding of its function in fish and how it integrates with other hormones is incomplete due to the high diversity of this group of animals and a still limited amount of available data. This study examined the temporal and spatial changes in expression of kisspeptin, gonadotropins and their respective receptors in the Senegalese sole during a full reproductive cycle. Kiss2 and kiss2r expression was determined by qRT-PCR in the forebrain and midbrain while expression of fshβ and lhβ was determined in the pituitary and fshr and lhr in the gonads. Plasma levels of testosterone (T), 11-ketotestosterone (11-KT) and estradiol-17β were measured by ELISA and gonadal maturation was assessed histologically. In males, kiss2 and kiss2r expression in the brain areas examined was highest towards the end of winter, just before the spawning season, which took place the following spring. This coincided with maximum levels of pituitary fshβ and lhβ, plasma T and 11-KT and the highest number of maturing fish. However, these associations were not evident in females, since the highest expression of kiss2, kiss2r and gonadotropins were observed in the fall, winter or spring, depending upon the variable and tissue considered. Taken together, these data show not only temporal and spatial, but also sex-specific differences in the expression of kisspeptin and its receptor. Thus, while expression of kiss2 in Senegalese sole males agrees with what one would expect according to its proposed role as a major regulator of the onset of reproduction, in females the situation was not so clear, since kiss2 and kiss2r expression was highest either before or during the spawning season.


The glutathione peroxidase homologous gene Gpxh in Chlamydomonas reinhardtii is upregulated by singlet oxygen produced in photosystem II.
The expression of the glutathione peroxidase homologous gene Gpxh, known to be specifically induced by the formation of singlet oxygen (1O2), was analyzed in cells of Chlamydomonas reinhardtii exposed to environmental conditions causing photoinhibition. Illumination with high light intensities, leading to an increased formation of 1O2 in photosystem II, continuously induced the expression of Gpxh in cell for at least 2 h. Phenolic herbicides like dinoterb, raise the rate of 1O2 formation by increasing the probability of charge recombination in photosystem II via the formation of the primary radical pair and thereby 3P680 formation (Fufezan C et al. 2002, FEBS Letters 532, 407-410). In the presence of dinoterb the light-induced loss of the D1 protein in C. reinhardtii was increased and the high light-induced Gpxh expression was further stimulated. DCMU, a urea-type herbicide, causing reduced 1O2 generation in photosystem II, protected the D1 protein slightly against degradation and downregulated the expression of the Gpxh gene compared to untreated cells exposed to high light intensities. This indicates that the Gpxh expression is induced by 1O2 under environment conditions causing photoinhibition.


Monthly-scale hydro-climatic forecasting and climate change impact evaluation based on a novel DCNN-Transformer network.
Climate change has emerged as one of the foremost global challenges confronting humanity today, leading to a heightened frequency and intensity of extreme weather phenomena, including droughts, floods, and erratic rainfall patterns. Accurately predicting changes in runoff patterns under future climate conditions holds significant importance for effective regional water resource planning and management. Recent research on runoff forecast has centered on optimizing hyperparameters of ELM, RNN, LSTM models using PSO, GWO, SSA, and other algorithms. Additionally, key features are extracted through input variable decomposition and preprocessing methods like EMD, EEMD, and VMD. However, these approaches have difficulties in extracting the long-term dependencies information of sequence units, parallel computing, and hyperparameter sensitivity. To address these shortcomings, this study proposes a novel end-to-end deep runoff prediction model based on deep convolutional neural network and Transformer (DCTN). The deep convolutional modules of DCTN employs the deep convolutional operation to extract local features of climate data while the Transformer of DCTN makes full use of self-attention to capture the long-term dependencies, which can achieve more accurate runoff predictions. Experiments on historical runoff forecasting at the Shanjiaodi hydrology station in the Dagu River Basin show that the proposed DCTN obtains a notable improvement of approximately 30.9% compared to traditional models. Based on the prediction results of three shared socioeconomic pathways, the potential impacts of climate change on runoff in Dagu River Basin were evaluated using the DCTN model. The results reveal that the likelihood of spring floods is substantially amplified in the mid-century and late-century, while the probability of extreme summer runoff diminishes. This study advances the understanding of runoff prediction and its implications under changing climate scenarios, paving the way for more informed decision-making and effective water resource management strategies.


Breast-milk derived potential probiotics as strategy for the management of childhood obesity.
Obesity and overweight, and their concomitant metabolic diseases, emerge as one of the most severe health problems in the world. Prevention and management of obesity are proposed to begin early in childhood, when probiotics may have a role. The Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), in a dynamic validated in vitro system able to simulate the different parts of the gastrointestinal tract, has proven to be useful in analyzing the human intestinal microbial community. L. plantarum 73a and B. animalis subsp. lactis INL1, two strains isolated from breast milk, were assayed in the SHIME® using the fecal microbiota of an obese child. L. plantarum 73a alone or in combination with B. animalis subsp. lactis INL1 demonstrated survival capacity in the SHIME® system. The administration of both strains increased the alpha diversity of the microbiota and reduced the levels of the phylum Proteobacteria. In particular, the genera Escherichia, Shigella, and Clostridium_sensu_stricto_1 were significantly reduced when both strains were administered. The increase of Proteobacteria phylum is generally associated with the microbiota of obese people. Escherichia and Shigellacan be involved in inflammation-dependent adiposity and insulin resistance. L. plantarum73a supplementation reduced ammonia production. L. plantarum 73a alone or in combination with B. animalis subsp. lactis INL1 are potential probiotic candidates for the management of infant obesity.


Effect of hypoxia duration on the oxygen-dependent production of a recombinant protein, β-galactosidase, by an animal cell line, F6D2, with a hypoxia-inducible enhancer.
Expression of specific genes is a strategy of animal cells for adaptation to oxygen deficiency and the mechanism underlying the hypoxic activation of gene expression may be useful for efficient production of recombinant proteins by animal cells, because oxygen is a limiting factor in animal cell cultures. We prepared an animal cell line harboring the plasmid in which expression of a reporter gene, β-galactosidase, is controlled by an enhancer responsible for the hypoxic activation of gene transcription. The purpose of this paper is to understand this hypoxic production of recombinant proteins quantitatively by a mathematical model originally developed based on the following hypotheses; 1 lacZ (the reporter gene) is transcribed after HIF-1 protein complex is bound to the hypoxic enhancer, 2. β-galactosidase synthesis rate is limited at the transcription of lacZ, 3. HIF-1 is an inactive form under a normal oxygen concentration, 4. Oxygen works as a repressor in the synthesis of HIF-1 protein, 5. Both β-galactosidase and HIF-1 are decomposed according to the first order reaction. The effects of hypoxic duration as well as oxygen concentration on the β-galactosidase production were successfully predicated by the model.


Metastatic choriocarcinoma simulating an arteriovenous malformation on chest radiography and dynamic CT.
A metastatic choriocarcinoma of the right lower lung simulated an arteriovenous malformation on chest radiography and dynamic CT.


Electronic medical records and health care transformation.
Effective electronic medical care record (EMR) systems will make a critical contribution to health care transformation. However, we need to know more about the total costs of EMRs and the ways in which they will interact with existing health care systems to make compelling predictions about their clinical benefits or the savings they can enable.


Isolation of natural products by preparative high performance liquid chromatography (prep-HPLC).
Preparative HPLC (prep-HPLC) has emerged as a mainstay of natural products isolation and purification. The various modes available to date, e.g. normal phase, reversed-phase, size exclusion, and ion exchange, can be used to purify most classes of natural products. This chapter presents an overview of the different modes along with a practical guide as to how to purify a natural product using the most robust and widely used of the modes, namely reversed-phase prep-HPLC. Instrumentation set-up and detection methods, sample preparation, method development, and sample work up are also discussed.


[Cerebrovascular malformation revealed during the prethrombolysis workup in acute ischemic stroke. Impact on therapeutic decision making].
Intravenous recombinant tissue plasminogen activator for acute ischemic stroke is contraindicated in patients harboring an asymptomatic intracranial vascular malformation, whether it is incidentally discovered at the time of the initial cerebral imaging or previously known. Because thrombolysis is associated with a risk of serious intracerebral hemorrhage, it is theoretically possible that this treatment increases the risk of bleeding or rupture of these malformations. However, this risk seems very low in clinical practice. We report two cases, one with a probable brainstem cavernous malformation treated with alteplase for a supratentorial ischemic stroke who developed just after treatment a fatal brainstem hemorrhage, and another one with asymptomatic dural arteriovenous fistula, treated by endovascular thrombectomy solely. This approach was safe and effective, and the patient had an endovascular embolization of the fistula one month later as it became symptomatic. Based on the literature, we discuss the bleeding risk of asymptomatic intracranial vascular malformations in acute ischemic stroke patients treated with alteplase, depending on the type of malformation (intracranial aneurysm, arteriovenous and cavernous malformation or fistula), and the alternative therapeutic options.


[New international reference values for spirometry: implications for clinical issues using a comparative analysis of a paediatric population].
The new lung function reference values of the global lung initiative (GLI) are recommended by most health societies. The aim of this study was to analyze FEV1- and FEV1/FVC-values from a German and Austrian patient group applying old and new reference values. A total of 215 Caucasian children (aged 5-17 years) were included. FEV1-values were significantly lower applying GLI reference values compared to Zapletal values (median 96.9 % pred. (87.3-105.2) versus 100.6 % pred. (quartile 91.5-111.4), p = 0.000), the median difference was 4.9 % (range -12.9 to 27.5) % pred. Differences correlated significantly with age and FEV1 in % predicted (Zapletal), p = 0.000 17/70 (24 %) patients with cystic fibrosis had FEV1-values <80% pred. applying Zapletal, in 25 (36 %) patients FEV1 was abnormal (z-score <1645) using GLI values; 3/145 asthmatics (2 %) had FEV1-Werte <80 % d.S. (Zapletal), 7/145 (5 %) z-scores <1645 (GLI). Differences between GLI-and Zapletal-reference values were considerable in pediatric asthma and CF-patients.


Electroneutral cation-chloride cotransporters in the central nervous system.
Several members of the cation-chloride cotransporter (solute carrier family 12, SLC12) gene family are expressed within the central nervous system, with one family member, the K+-Cl- cotransporter KCC2, exclusive to neurons. These transporters are best known for their roles in cell volume regulation and epithelial salt transport, but are increasingly receiving attention in neuroscience. In particular, intracellular chloride activity and hence the neuronal response to GABA and glycine appears to be determined by a balance between chloride efflux and influx through KCC2 and the Na+-K+-2Cl- cotransporter NKCC1, respectively. This relationship has important implications for neuronal development, sensory perception, neuronal excitability, and the response to neuronal injury. Finally, the association between loss of function in the K+-Cl- cotransporter KCC3, with a severe peripheral neuropathy associated with agenesis of the corpus callosum, has revealed an unexpected role for K+-Cl- cotransport in the development and/or maintenance of both the central and peripheral nervous systems.


Elevated tear interleukin-6 levels in patients with Sjögren syndrome.
The purpose of the study was to investigate interleukin-6 (IL-6) levels in the tear fluid and sera of patients with Sjögren syndrome (SS). Twelve patients with primary SS and 12 normal control subjects participated. Tear fluid and sera were obtained from the study and the control groups. Evaluation of tear fluid and sera IL-6 levels was done by using a quantitative enzyme-linked immunosorbent assay kit. All assays were carried out blindly with respect to diagnosis. Tear fluid IL-6 levels were measured. The mean concentration (+/- standard error) of IL-6 in the tears of patients with SS was elevated significantly compared to that of normal control subjects (88.6+/-16.2 vs. 42.1+/-10.6 pg/ml; P < 0.05). No significant differences were noted in the serum IL-6 levels between the two groups. A significant correlation (r = 0.742, P = 0.006) was found between tear fluid IL-6 levels and the focus score of lip biopsy specimens in patients with SS. Tear fluid IL-6 levels may serve as an important marker for tear gland involvement in SS.


Optimal foraging: a bird in the hand released.
Optimal foraging theory aims to elucidate strategies that maximize resource intake. Although traditionally used to understand animal foraging behavior, recent evolutionary experiments with viruses offer a new twist on an old idea.


Identification of potential inhibitors of cholinergic and β-secretase enzymes from phytochemicals derived from Gongronema latifolium Benth leaf: an integrated computational analysis.
Neurodegenerative disorders (NDDs) are associated with increased activities of the brain acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-secretase enzyme (BACE1). Inhibition of these enzymes affords therapeutic option for managing NDDs such as Alzheimer's disease (AD) and Parkinson's disease (PD). Although, Gongronema latifolium Benth (GL) has been widely documented in ethnopharmacological and scientific reports for the management of NDDs, there is paucity of information on its underlying mechanism and neurotherapeutic constituents. Herein, 152 previously reported Gongronema latifolium derived-phytochemicals (GLDP) were screened against hAChE, hBChE and hBACE-1 using molecular docking, molecular dynamics (MD) simulations, free energy of binding calculations and cluster analysis. The result of the computational analysis identified silymarin, alpha-amyrin and teraxeron with the highest binding energies (-12.3, -11.2, -10.5 Kcal/mol) for hAChE, hBChE and hBACE-1 respectively as compared with those of the reference inhibitors (-12.3, -9.8 and - 9.4 for donepezil, propidium and aminoquinoline compound respectively). These best docked phytochemicals were found to be orientated in the hydrophobic gorge where they interacted with the choline-binding pocket in the A-site and P-site of the cholinesterase and subsites S1, S3, S3' and flip (67-75) residues of the pocket of the BACE-1. The best docked phytochemicals complexed with the target proteins were stable in a 100 ns molecular dynamic simulation. The interactions with the catalytic residues were preserved during the simulation as observed from the MMGBSA decomposition and cluster analyses. The presence of these phytocompounds most notably silymarin, which demonstrated dual high binding tendencies to both cholinesterases, were identified as potential neurotherapeutics subject to further investigation.


Revisiting the multidimensional interaction model of stress, anxiety and coping during the COVID-19 pandemic: a longitudinal study.
Although the Multidimensional Interaction Model of Stress, Anxiety and Coping (MIMSAC) has been known for years, there is a lack of research examining this theory longitudinally in stressful events. This study aims to revisit the MIMSAC among university students during the COVID-19 pandemic. A prospective cohort study with the longitudinal design was performed during the first (W1, March 30-April 29, 2020) and second wave (W2, November 3-December 3, 2020) of the COVID-19 pandemic. A total of 216 university students with a mean age of 22 years (ranging from 20 to 36, M = 22.13, SD = 2.04) participated in the study. An online survey included Perceived Stress Scale, Coping Inventory for Stressful Situations, and Generalized Anxiety Disorder. Due to the MIMSAC, all variables changed substantially across W1 and W2, adapting to an unpredictable environment. Women scored higher than men in stress, anxiety, emotion- and avoidance-oriented coping styles. We found the indirect effect of emotion-oriented coping on the stress-anxiety relationship and task-oriented coping on the anxiety-stress interaction. Avoidance was not found as a mediator in the stress-anxiety interaction. Emotion-oriented coping adversely affected mental health, increasing anxiety in response to stress during the COVID-19 pandemic. Task-oriented coping efficiently decreased stress in reaction to high anxiety, but only in men. Avoidance seems to be an ineffective coping style during the COVID-19 pandemic. Campus intervention programs should focus on reducing negative emotions and increasing the frequency of task-oriented coping strategies among university students.


RoBDEMAT: A risk of bias tool and guideline to support reporting of pre-clinical dental materials research and assessment of systematic reviews.
To develop a risk of bias tool for pre-clinical dental materials research studies that aims to support reporting of future investigations and improve assessment in systematic reviews. A four-stage process following EQUATOR network recommendations was followed, which included project launch, literature review, Delphi process and the tool finalization. With the support of the European Federation of Conservative Dentistry (EFCD) and the Dental Materials Group of the International Association for Dental Research (DMG-IADR), a total of 26 expert stakeholders were included in the development and Delphi vote of the initial proposal. The proposal was built using data gathered from the literature review stage. During this stage, recent systematic reviews featuring dental materials research, and risk of bias tools found in the literature were comprehensively scanned for bias sources. The experts thus reached a consensus for the items, domains and judgement related to the tool, allowing a detailed guide for each item and corresponding signalling questions. The tool features nine items in total, spread between 4 domains, pertaining to the following types of bias: bias related to planning and allocation (D1), specimen preparation (D2), outcome assessment (D3) and data treatment and outcome reporting (D4). RoBDEMAT, as presented, features signalling questions and a guide that can be used for RoB judgement. Its use as a checklist is preferred over a final summary score. RoBDEMAT is the first risk of bias tool for pre-clinical dental materials research, supported and developed by a broad group of expert stakeholders in the field, validating its future use. This new tool will contribute the study field by improving the scientific quality and rigour of dental materials research studies and their systematic reviews. Such studies are the foundation and support of future clinical research and evidence-based decisions.


Haemorrhagic fever virus activity in equatorial Africa: distribution and prevalence of filovirus reactive antibody in the Central African Republic.
Seroepidemiological surveys were conducted to determine the frequency and distribution of haemorrhagic fever virus (HFV) activity in the Central African Republic. Human serum specimens (4295) were collected from 5 ecologically distinct zones. Serological evidence of HFV activity was found in all the zones. The filovirus antibody prevalence (24.4%, 1051/4295) was greater than the combined prevalence for Lassa virus, Rift Valley fever virus and Crimean-Congo HFV antibody (1.1%, 45/4295; P < 0.01). Evidence of filovirus activity was found in all zones: 21.3% (914/4295) of the population were seropositive for Ebola virus antibody while only 3.2% (137/4295) were seroreactive with Marburg viral antigens. Age and sex were important host-related factors influencing filovirus activity, particularly in dry grassland and moist forest communities. These communities shared many factors, but differences, such as agricultural practices and ethnic backgrounds, may also affect the risk of infection. Filovirus infections appear to occur without apparent disease. Continued investigations are needed to evaluate the true pathogenicity of the African filoviruses and the likelihood that unidentified serologically cross-reacting and non-pathogenic members of the filovirus family are active in equatorial Africa.


Tissue elastic properties of eight Hawaiian Dubautia species that differ in habitat and diploid chromosome number.
Eight Hawaiian Dubautia species grow in habitats as varied as exposed lava, dry scrub, mesic forest, wet forest, and bog. These species also differ in diploid chromosome number, with four species having 13 pairs of chromosomes and four species having 14 pairs. This ecological and chromosomal variation is paralleled by significant interspecific variation in tissue elastic properties. The four 13-paired species from dry habitats exhibit significantly lower tissue elastic moduli near full hydration (E i) than the four 14-paired species from mesic to wet habitats. Values of E i range from 2 to 4 MPa among the former species and from 9 to 18 MPa among the latter species. The turgor dependence of the elastic modulus also differs markedly between the two groups of species. As a result of these differences in tissue elastic properties, the capacity for maintaining high turgor pressures as tissue water content decreases is much greater in the 13-paired species from dry habitats than in the 14-paired species from mesic to wet habitats. These results indicate that the evolutionary diversification of the Dubautia species has been accompanied by a significant degree of change at the physiological level.


A meta-analysis comparing breast conservation therapy alone to the oncoplastic technique.
When immediate reconstruction is applied to breast conservation therapy (BCT), the benefits extend well beyond the minimization of poor cosmetic results. The purpose of this analysis was to compare literature outcomes between BCT alone and BCT with the oncoplastic approach. A meta-analysis was performed in PubMed using key words "oncoplastic," "partial breast reconstruction," and "breast conservation therapy." Case reports, series with less than 10 patients, and those with less than 1-year follow-up were excluded from the analysis. The 3 comparative groups included BCT with oncoplastic reduction techniques (Group A), BCT with oncoplastic flap techniques (Group B), and BCT alone (Group C). Comparisons were made on 3165 patients in the BCT with oncoplastic group (Groups A and B, 41 papers) and 5494 patients in the BCT alone group (Group C, 20 papers). Demographics were similar, and tumor size was larger in the oncoplastic group (2.7 vs 1.2 cm). The weight of the lumpectomy specimen was 4 times larger in the oncoplastic group. The positive margin rate was significantly lower in the oncoplastic group (12% vs 21%, P < 0.0001). Reexcision was more common in the BCT alone group (14.6% vs 4%, P < 0.0001), however, completion mastectomy was more common in the oncoplastic group (6.5% vs 3.79%, P < 0.0001). The average follow-up was longer in the BCT alone group (64 vs 37 months). Local recurrence was 4% in the oncoplastic group and 7% in the BCT alone group. Satisfaction with the aesthetic outcome was significantly higher in the oncoplastic group (89.5% vs 82.9%, P < 0.001). The oncoplastic approach to BCT allows a generous resection with subsequent reduction in positive margins. The true value on local recurrence remains to be determined. Patients are more satisfied with outcomes when the oncoplastic approach is used.


Fiberoptic bronchoscopy--diagnostic applications.
Bronchoscopy has an important role in the diagnosis and staging of lung cancer. It is also useful in a more limited role in the diagnosis of infectious, interstitial, and pediatric diseases. Its applications, limitations, and complications in these conditions are reviewed.


Microbiome complexity and Staphylococcus aureus in chronic rhinosinusitis.
The aim of this study was to compare microbiological culture-based and culture-independent (16S rRNA gene sequencing) methodologies for pathogen identification in chronic rhinosinusitis (CRS) patients. We hypothesized that bacterial culture and DNA sequencing would yield largely concurrent results, although sequencing would detect greater bacterial diversity, and the sinonasal microbiomes of CRS patients would differ in composition and diversity compared with non-CRS controls. Cross-sectional observational study. Middle meatus swabs from CRS patients collected during endoscopic sinus surgery were analyzed by both clinical culture and broad-range analysis of 16S rRNA gene pyrosequences. A total of 21 swab samples from 15 CRS patients and five non-CRS controls were analyzed. One CRS patient was also swabbed 3 weeks postoperatively due to evidence of purulence during a clinical visit. All subjects had positive bacterial cultures, with a mean of 2.8 isolates per subject. The most prevalent cultivars were coagulase-negative staphylococci (15/20 specimens, 75%), Staphylococcus aureus (10/20, 50%), and Propionibacterium acnes (6/20, 30%). Among 57,407 pyrosequences generated, the most prevalent were from coagulase-negative staphylococci (21/21 specimens, 100%), Corynebacterium spp (18/21, 85.7%), P acnes (16/21, 76.2%), and S aureus (14/21, 66.7%). Bacterial diversity correlated with recent antibiotic use, asthma, prior sinus surgery, and relative abundance of S aureus. DNA pyrosequencing revealed greater biodiversity than culture, although in most cases culture results represented a subset of the abundant DNA sequence types. CRS patients were characterized by altered microbial composition (P = .02) and greater abundance of S aureus (P = .03).


Affine Subspaces of Curvature Functions from Closed Planar Curves.
Given a pair of real functions (k, f), we study the conditions they must satisfy for k + λ f to be the curvature in the arc-length of a closed planar curve for all real λ . Several equivalent conditions are pointed out, certain periodic behaviours are shown as essential and a family of such pairs is explicitely constructed. The discrete counterpart of the problem is also studied.


Inherited defects causing hemophagocytic lymphohistiocytic syndrome.
Hemophagocytic lymphohistiocytosis (HLH) manifests as the uncontrolled activation of T lymphocytes and macrophages infiltrating multiple organs. Molecular studies of individuals with HLH have demonstrated in most of these conditions a critical role of granule-dependent cytotoxic activity in the regulation of lymphocyte homeostasis, and have allowed the characterization of key effectors regulating cytotoxic granule release. The cytolytic process may now be considered a multistep process, including cell activation; the polarization of cytotoxic granules toward the conjugated target cell; the tethering, priming, and fusion of the cytotoxic granules with the plasma membrane; and the release of their contents (perforin and granzymes) into the intercellular cleft, leading to target cell death. Cytolytic cells have a second effector function involving the production of cytokines, principally γ-interferon, which is secreted independently of the exocytosis cytotoxic granule pathway. An analysis of the mechanisms underlying HLH has identified γ-interferon as a key cytokine inducing uncontrolled macrophage activation, and thus represents a potential therapeutic target.


Further purification, characterization and salt activation of acyl-CoA synthetase from Escherichia coli.
Acyl-CoA synthetase was further purified from Escherichia coli in good yield and fold purification by affinity chromatography on CoA-Sepharose 4B. The molecular weight of the active form of the purified enzyme was estimated as 45 000 by Sephadex G-100 and 47 000 by Sephadex G-200. Sedimentation equilibrium ultracentrifugation analysis revealed a molecular weight of 50 000. The sedimentation coefficient was calculated as 4.4 S. An absorption maximum at 276 nm was observed in the ultraviolet light absorption spectrum. The molar extinction coefficient was 9.2 X 10(4). Kinetic constants were determined for trans fatty acids. All ions tested, including chaotropic and lyotropic ions, stimulated or inhibited acyl-CoA synthetase activity depending on their concentrations in the assay system. In a series of chaotropes, the lower concentration required to maximally activate acyl-CoA synthetase in increasing order of potency of chaotropic ions. The inhibitory effect of chaotrope on the enzyme activity was reversible. These data suggest that salts have a common mode of action and influence acyl-CoA synthetase activity primarily through their effect on the solution structure.


Prediction of protein folding pathways: Bovine pancreatic trypsin inhibitor.
A previous theory for the prediction of protein folding pathways [1] is applied to bovine pancreatic trypsin inhibitor and the resulting sequence of folding events shown to corroborate well with available experimental data.


Experimental models of HD and reflection on therapeutic strategies.
Huntington's disease (HD) is an autosomal dominant, progressive, and fatal neurodegenerative disorder caused by an expanded polyglutamine cytosine-adenine-guanine repeat in the gene coding for the protein huntingtin. Despite great progress over the past two decades since the identification of the gene mutation, a direct causative pathway from the HD gene mutation to neuronal dysfunction and death has not yet been established. One important advance in understanding the pathogenic mechanisms of this disease has been the development of experimental mouse models that replicate many of the clinical, neuropathological, and molecular events in HD patients. These murine models have played a critical role in providing accurate and experimentally accessible systems to study multiple features of disease pathogenesis and to test potential therapeutic strategies. A better understanding of the pathophysiological mechanisms of disease and how they interrelate has become important in identifying a treatment for HD and in the design of human clinical trials. In this chapter, we review the current state of HD mouse models and their successes in elucidating disease pathogenesis and in developing pharmacotherapies. There is no clinically proven treatment for HD that can halt or ameliorate the inexorable disease progression. As such, a guide to assessing studies in mouse models and salient issues related to translation from mice to humans are included.


Determination of donor-type chimerism using a semi-quantitative PCR-based method in a canine model for bone marrow transplantation.
Dogs are used in preclinical transplantation models to study methods of allogeneic bone marrow transplantation (BMT). The evaluation of chimerism is of major significance for the investigation of graft-vs.-host (GvH) and host-vs.-graft (HvG) reactions. To detect and quantitate male donor cells after a sex-mismatched (male to female) allogeneic BMT, we established a semi-quantitative polymerase chain reaction (PCR) assay. Based on the canine Y-chromosome sex-determining region (Sry) sequence, we designed primer specific for the detection of male DNA and optimised PCR conditions and cycle numbers. Artificial mixtures of male and female leukocytes were used to analyse the sensitivity of the assay. To validate our established method, we determined the percentage of chimerism in three transplanted female dogs. Under optimised conditions, the established PCR assay specifically detected male cells down to 0.01%, which corresponds to 0.1ng of transplanted male DNA. The percentage of chimerism could be quantitated either by agarose gel analysis or Southern blot analysis. Using our assay, we could confirm the percentage of chimerism in blood samples of three transplanted female canines, previously determined by karyotype analysis as 0, 100 and 100%, respectively. The established semi-quantitative PCR assay offers a quick, simple, accurate and sensitive way of evaluating and quantitating the percentage of chimerism in a sex-mismatched canine BMT model.


Isolation and characterization of 13 microsatellite loci for the Neotropical otter, Lontra longicaudis, by next generation sequencing.
The Neotropical otter, Lontra longicaudis, is an ecologically important species for freshwater ecosystems that is threatened due to habitat destruction and hunting. However, there is limited information regarding the population sizes, genetic diversity, genetic structure and gene flow of the species, which is crucial for the elaboration of conservation plans. The aim of this study was to isolate and characterize microsatellites for L. longicaudis, using Illumina paired-end-sequencing. Initial amplification tests were performed in 48 loci, out of which, 13 yielded high-quality PCR products and thus were further evaluated. Genetic diversity and discrimination power of the 13 microsatellite loci was assessed using 19 non-invasive samples collected in the Jamapa basin in Veracruz, Mexico and blood samples from six captive individuals. All loci were polymorphic, the number of alleles per locus ranged from 4 to 10, the observed heterozygosity from 0.21 to 0.69, and the expected heterozygosity from 0.55 to 0.82. The combined set of 13 microsatellites showed a high power for discriminating among individuals (probability of identity PID = 1.551 × 10-16) and among siblings (probability of identity of siblings PIDSIB = 3.349 × 10-06). A combination of nine loci are sufficient to discriminate among siblings with high confidence (PIDSIB < 0.0001). The new set of microsatellites for the Neotropical otter reported here will provide a useful genetic tool to assess population genetic patterns and ecological parameters of the species.