Spatial Distribution and Factors Associated with Khat Chewing among Adult Males 15-59 Years in Ethiopia Using a Secondary Analysis of Ethiopian Demographic and Health Survey 2016: Spatial and Multilevel Analysis.
Khat chewing has become prevalent in the world due to the improvement of road and air transportation. In Ethiopia, khat chewing is more prevalent and widely practiced by men. Khat has a negative effect on social, economic, and mental health. There is variation in khat cultivation, use, and factors that associated with khat chewing in the Ethiopian regions. Therefore, this study is aimed at showing spatial distribution and factors associated with khat chewing among male adults 15-59 years in Ethiopia. A total of 12,594 men were included in this study. ArcGIS version 10.7 software was used to show the spatial distribution of chewing khat among adult men in Ethiopia. The Bernoulli model was applied using Kilduff SaTScan version 9.6 software to identify significant purely spatial clusters for chewing khat in Ethiopia. A multilevel logistic regression model was fitted to identify factors associated with khat chewing. A P value < 0.05 was taken to declare statistically significant predictors. The EDHS 2016 survey showed that the high proportion of chewing khat was found in Dire Dawa, Harari, Southern Oromia, Somali, and Benishangul Gumuz regions. In spatial scan statistics analysis, a total of 126 clusters (LLR = 946.60, P value < 0.001) were identified. Age group 30-44 years old (AOR = 1.60, 95% CI: 1.37, 1.86) and 45-59 years old (AOR = 1.33, 95% CI: 1.09, 1.61), being single (AOR = 1.86, 95% CI: 1.64, 2.12), Muslim religion followers (AOR = 15.03, 95% CI: 11.90, 18.90), media exposed (AOR = 0.77, 95% CI: 0.68, 0.86), had work (AOR = 2.48, 95% CI: 2.08, 2.95), alcohol drinker (AOR = 3.75, 95% CI: 3.10, 4.53), and region (Afar, Amhara, Benishangul Gumuz, Gambela, Harari, Oromia, Somali, Southern Nations, Nationalities, and People's Region (SNNPR), and Tigray) and two cities (Addis Ababa and Dire Dawa) were statistically significant factors affecting chewing khat in Ethiopia. In Ethiopia, the spatial distribution of khat chewing among adult men was nonrandom. A high proportion of khat chewing was observed in Dire Dawa, Harari, Southern Oromia, Somali, and Benishangul Gumuz regions. Older age group, being single marital status, alcohol drinker, media unexposed, had no work, and Muslim religion follower were factors affecting khat chewing. Policymakers should be given spatial attention in reducing the prevalence of chewing khat by teaching the health impact of khat chewing through media in the identified regions.


Porcine blood cell concentrates for food products: hygiene, composition, and preservation.
The objective of this study was to determine whether porcine blood cell concentrates (BCC) can be produced and stored using hygienic measures independent of the temperature acting upon the substrate. A number of additives widely accepted by the consumer (NaCl, sugars, food-grade acids) were used to form so-called hurdles (water activity [a(w)], pH) to spoilage, and their impact was tested on microbiological and sensory parameters of the BCC. BCC, whole blood, plasma, and the anticoagulant were collected on 23 days in a slaughterhouse. The BCC with the additives were stored for 27 days at + 3 degrees C and at +20 degrees C. Microbiological and chemical tests were carried out on the raw materials, and a(w) and the pH values of the stored BCC combinations were determined; the combinations were also submitted to sensory testing. The amounts of protein (33.4%) and hemoglobin (29.5 g/dl) in the BCC were significantly higher than in whole blood (19.4%; 13.8 g/dl). The mean total aerobic plate count was similar in all three substrates. However, the highest count (4.83 log CFU/g) was found in BCC; the count was lower in whole blood (4.62 log CFU/g) and lowest in plasma (4.22 log CFU/g). Storability (defined as a count of <5 log CFU/g) for 27 days at +20 degrees C was achieved only with two additive types: 15% NaCl and 10% NaCl plus 10% glucose plus 1% of a food-grade acid. Spoilage of the BCC was inhibited by an a(w) of 0.824 (with 15% NaCl) and by the combination of a(w) 0.87 and a pH of 5 (with 10% NaCl, 10% sugar, 1% acid). Both substrates retained their red color and fresh odor over the entire storage time.


Ordering of solid microparticles at liquid crystal-water interfaces.
We report a study of the organization of solid microparticles at oil-water interfaces, where the oil is a thermotropic liquid crystal (LC). The study was motivated by the proposition that microparticle organization and LC ordering would be coupled at these interfaces. Surfactant-functionalized polystyrene microparticles were spread at air-water interfaces at prescribed densities and then raised into contact with supported films of nematic 4-pentyl-4'-cyanobiphenyl (5CB). Whereas this method of sample preparation led to quantitative transfer of microparticles from the air-water interface to an isotropic oil-water interface, forces mediated by the nematic order of 5CB were observed to rapidly displace microparticles laterally across the interface of the water upon contact with nematic 5CB, thus leading to a 65% decrease in the density of microparticles at the LC-water interface. These lateral forces were determined to be caused by microparticle-induced deformation of the LC, the energy of which was estimated to be approximately 10(4) kT. We also observed microparticles transferred to the LC-water interface to assemble into chainlike structures that were not seen when using isotropic oils, indicating the presence of LC-mediated interparticle interactions at this interface. Optical textures of the LC in the vicinity of the microparticles were consistent with formation of topological defects with dipolar symmetry capable of promoting the chaining of the microparticles. The presence of microparticles at the interface also impacted the ordering of the LCs, including a transition from parallel to perpendicular ordering of the LC with increasing microparticle density. These observations, when combined, demonstrate that LC-mediated interactions can direct the assembly of solid microparticles at LC-water interfaces and that the ordering of the LC is also strongly coupled to the presence of microparticles.


Purification and characterisation of D-glucose oxidase from white-rot fungus Pleurotus ostreatus.
D-Glucose oxidase was purified 27.5-fold to apparent homogeneity with an overall yield of 23.8%, from Pleurotus ostreatus, through a purification procedure of ammonium sulphate precipitation, gel-permeation, anion-exchange and hydrophobic-interaction chromatography. The molecular mass determined by gel filtration was found to be 290 kDa. SDS/PAGE revealed that the enzyme consists of four subunits with a molecular mass of 70 kDa. The absorption spectra of the enzyme exhibit maxima at 280, 360 and 460 nm. The enzyme shows a fluorescence spectrum with an excitation maximum at 470 nm and an emission maximum at 530 nm. These results indicate that the prosthetic group of the enzyme is flavin and that the enzyme contains 4 mol flavin/mol enzyme. The enzyme is optimally active at 50 degrees C and at pH 5.5-6.0. It exhibits broad affinity for various sugars and specificity for D-glucose with Km value of 1.34 mM. 2,6-Dichloroindophenol, Wurster's blue, and 4-benzoquinone can function as electron acceptors but phenazine methosulphate cannot function as an electron acceptor. The enzyme is inhibited completely by mercuric chloride and partially by silver sulphate, sodium azide 8-hydroxyquinoline.


Retrofusion of intralumenal MVB membranes parallels viral infection and coexists with exosome release.
The endosomal system constitutes a highly dynamic vesicle network used to relay materials and signals between the cell and its environment.1 Once internalized, endosomes gradually mature into late acidic compartments and acquire a multivesicular body (MVB) organization through invagination of the limiting membrane (LM) to form intraluminal vesicles (ILVs).2 Cargoes sequestered into ILVs can either be delivered to lysosomes for degradation or secreted following fusion of the MVB with the plasma membrane.3 It has been speculated that commitment to ILVs is not a terminal event, and that a return pathway exists, allowing "back-fusion" or "retrofusion" of intraluminal membranes to the LM.4 The existence of retrofusion as a way to support membrane equilibrium within the MVB has been widely speculated in various cell biological contexts, including exosome uptake5 and major histocompatibility complex class II (MHC class II) antigen presentation.6-9 Given the small physical scale, retrofusion of ILVs cannot be measured with conventional techniques. To circumvent this, we designed a chemically tunable cell-based system to monitor retrofusion in real time. Using this system, we demonstrate that retrofusion occurs as part of the natural MVB lifestyle, with attributes parallel to those of viral infection. Furthermore, we find that retrofusion and exocytosis coexist in an equilibrium, implying that ILVs inert to retrofusion comprise a significant fraction of exosomes destined for secretion. MVBs thus contain three types of ILVs: those committed to lysosomal degradation, those retrofusing ILVs, and those subject to secretion in the form of exosomes. VIDEO ABSTRACT.


Metal binding characteristics and role of iron oxidation in the ferric uptake regulator from Escherichia coli.
The ferric uptake regulator is a metal-dependent transcription repressor that is activated by divalent transition metal cations. Fe(II) is believed to be the primary functional metal in vivo; however, the ability of other divalent cations to activate Fur brings into question the true physiological metal. Furthermore, the role of different oxidation states of iron in activating Fur has not been determined. Comparison of the affinity of different metals with intracellular metal concentrations would suggest which metals activate Fur in vivo; however, no accurate determinations of the affinity of Fur for metals have been reported. In this study, methods for reconstituting Fur with Fe(II), Fe(III), Co(II), and Zn(II) are described. Reconstituted protein was assayed for DNA affinity by gel shift assays. Fur is activated for DNA binding when reconstituted with Fe(III), as well as Fe(II), Zn(II), Co(II), and Mn(II), with little difference in DNA affinity for the different metallo forms of Fur. The affinity of Fur for the different metals was determined and ranges over several orders of magnitude in the following order: Zn(II) >> Co(II) > Fe(II) > Mn(II). Only Fe(II) binds with sufficient affinity to activate Fur significantly at physiological metal concentrations, when compared to previously determined total metal concentrations in Escherichia coli.


Disorders of childhood growth and development: screening and evaluation of the child who misses developmental milestones.
The family physician is one of the few individuals from whom families receive feedback about their children's development; this makes early identification of potential delays an important responsibility. The American Academy of Pediatrics recommends formal developmental screening for all children at the 9-, 18-, and 24- and/or 30-month well-child visits as well as developmental surveillance at every office visit through age 5 years. A formal screening measure is recommended, taking into account administration time and cost, characteristics of the patient population (eg, availability of screening tool in numerous languages), and psychometrics (eg, reliability, sensitivity, specificity). In the case of abnormal screening results, family physicians must determine the need for further medical evaluation (eg, by a developmental pediatric subspecialist or a pediatric neurology, genetics, or physiatry subspecialist) and/or further developmental evaluation (eg, by a physical therapy [PT], occupational therapy [OT], speech/language pathology, psychology, or audiology subspecialist). Knowledge of early intervention and early childhood programs is necessary for directing parents to evaluation and treatment sources. In treating patients with developmental delays, family physicians must possess knowledge regarding traditional modalities (eg, speech/language therapy, OT, PT) as well as newer treatments with less research support (eg, gluten-free/casein-free diet, hyperbaric oxygen therapy, neurodevelopmental treatment) that families may consider.


No clinical benefit from gender-specific total knee replacement implants: a systematic review.
Total knee arthroplasty (TKA) remains the treatment of choice for severe osteoarthritis of the knee and nearly 60% of patients undergoing TKA are women. Females present three notable anatomic differences. Thus, gender-specific (GS) components were introduced to accommodate the females' anatomic differences. No systematic review has been published since 2014. The aim of this study was to perform a recent systematic review of the literature to determine whether there is any clinical benefit of gender-specific implants compared to conventional unisex implants in total knee arthroplasty (TKA). This study included prospective randomized controlled trials (PRCTs) comparing clinical and radiological outcomes, and complications in TKA with gender-specific implants and conventional implants. All studies had a minimum follow-up of two years. Three PRCTs published between 2010 and 2012 were included. These studies showed a low risk of bias and were of very high quality. We did not find superior clinical outcomes for gender-specific prostheses compared to conventional prostheses. However, gender-specific TKA reduced the number of patients with femoral component overhang compared to conventional TKA. In our systematic review, despite a lower overhang rate, gender-specific implants in female TKA showed no clinical benefit over standard unisex implants. Good clinical results with significant improvement were observed with both designs. There is a notable absence of new studies on this subject in recent years, and further research needs to be performed using various gender-specific implant designs to further define the role of gender-specific implants. Systematic review, Level IV.


High-yield synthesis and properties of symmetrical comb-like ZnO nanostructures on aluminum foil substrate.
Highly-symmetrical well-crystallized comb-like ZnO nanostructures were grown in a very large-quantity on the aluminum foil via non-catalytic thermal evaporation method by using metallic zinc powder in the presence of oxygen at low temperature of 440 degrees C. Detailed morphological investigations revealed that the as-grown combs are made with a ribbon-like stem and aligned nanorod/nanowire arrays attached uniformly and nicely along one side of the ribbon-like stem. The X-ray diffraction (XRD) pattern and high-resolution transmission electron microscopy (HRTEM) revealed that the as-grown nanocombs are crystalline and possessing a wurtzite hexagonal phase. The optical properties were observed by room-temperature photoluminescence (PL) and Raman-scattering which exhibited good optical properties for the as-grown products. A plausible growth mechanism has also been proposed for the formation of highly symmetrical comb-like ZnO nanostructures.


Enhancing enzymatic hydrolysis of sugarcane bagasse by ferric chloride catalyzed organosolv pretreatment and Tween 80.
In this work, a FeCl3-catalyzed organosolv pretreatment was employed at 160 °C to remove hemicellulose and lignin in sugarcane bagasse leaving the cellulose-enriched residue for enzymatic hydrolysis to sugars. The solubilized hemicellulose fractions consisted more monomer xylose than oligomer xylose. The FeCl3-catalyzed organosolv pretreatment significantly improved the enzymatic hydrolysis, nearly 100% of cellulose components were converted to glucose after pretreatment with 0.05 M FeCl3. Structural analysis was employed to reveal how pretreatment affected the enzymatic hydrolysis. With the addition of Tween 80, the same level of glucose was obtained with 50% reduction of enzyme dosage after 24 h. Furthermore, the influence of Tween 80 on different pretreatment systems was investigated, indicating that the improvement was increased as the lignin content increased, decreased with high enzyme loading and extending hydrolysis time. This work suggested that the addition of Tween 80 could improve the enzymatic hydrolysis, reduce the hydrolysis time and enzyme dosage.


The role of skin substitutes in the management of chronic cutaneous wounds.
Chronic wounds, including diabetic and venous ulcers, represent disruption of normal healing processes resulting in a pathological state of nonhealing cutaneous inflammation. They place an increasingly significant economic burden on healthcare providers as their prevalence is rising in keeping with an aging population. Current treatment modalities are slow acting and resource intensive. Bioengineered skin substitutes from autogenic, allogenic, or xenogenic sources have emerged as a new and alternative therapeutic option. A range of such products is licensed for clinical use, which differ in terms of structure and cellular content. Placed directly onto a prepared wound bed, skin substitutes may stimulate or accelerate healing by promoting revascularization, cellular migration, and repopulation of wound fields through provision of an appropriate scaffold material to facilitate these processes. Products containing fetal or autologous cells also benefit from early release of bioactive molecules including growth factors and cytokines. To date, limited numbers of randomized controlled trials studying skin substitutes have been published but evidence from case series and case-control studies is encouraging. This review discusses chronic wound biology, the influence that skin substitutes can exert on this environment, the products currently available, and examines the evidence for their use in chronic wound management.


[Application of a modified vascular blocking technique in intrafascial nerve-sparing laparoscopic radical prostatectomy].
To investigate the clinical effect of a modified vascular blocking technique in intrafascial nerve-sparing laparoscopic radical prostatectomy (INLRP). We retrospectively studied the clinical data on 13 cases of INLRP completed via a modified vascular blocking technique between July 2021 and August 2022. The patients ranged in age from 64 to 73 (68.8 ± 3.15) years, with elevated PSA of 4.71-16.12 (9.71 ± 3.50) μg/L preoperatively. Prostate cancer was confirmed in all the cases by ultrasound-guided perineal prostate needle biopsy, with Gleason 6 in 7 cases and Gleason 7 in 6 cases. MRI revealed no preoperative tumor breakthrough in the prostatic capsule or pelvic lymph node metastasis. All the patients received INLRP with a modified superficial suture dorsal vein complex (DVC) combined with lateral prostatic pedicle vascular blocking. Prostatic capsule rupture occurred in 1 case during the operation, with positive resection margin indicated by rapid intraoperative frozen biopsy, so the lateral fascia resection was modified. No positive resection margin was found in any of the cases in postoperative pathological examinations. Urinary continence was restored in 8 cases immediately after surgery and in the other 5 within 2 weeks after catheter removal. At 1 month after surgery, all the patients were medicated with low-dose tadalafil (5 mg qd), and IIEF-5 scores of >15 were achieved in 4 cases (31%) at 1 month and in another 8 (62%) at 3 months postoperatively. INLRP via modified vascular blocking showed the advantages of desirable intraoperative bleeding control and postoperative tumor control, restoration of urinary continence and relatively satisfactory recovery of erectile function. However, due to the small sample size, short follow-up time and lack of control, our findings need to be further verified by more clinical studies.


Therapy-related myelodysplastic syndrome following acute promyelocytic leukemia and biphenotypic acute leukemia following stem cell transplantation in the same patient.
Therapy-related myelodysplastic syndrome in patients with acute promyelocytic leukemia is a rare event and the prognosis is poor. Allogeneic bone marrow transplantation is recently being reported as an effective treatment. We present a young patient with acute promyelocytic leukemia who developed myelodysplastic syndrome 52 months after complete remission. She underwent allogeneic peripheral blood stem cell transplantation but relapsed with biphenotypic leukemia after five months. To our knowledge, this is the first case to relapse with acute biphenotypic leukemia after allogeneic peripheral stem cell transplantation for therapy-related myelodysplastic syndrome following acute promyelocytic leukemia.


Implementation of a new blood cooler insert and tracking technology with educational initiatives and its effect on reducing red blood cell wastage.
The objective was to report a successful implementation of a blood cooler insert and tracking technology with educational initiatives and its effect on reducing red blood cell (RBC) wastage. The blood bank database was used to quantify and categorize total RBC units issued in blood coolers from January 2010 to December 2015 with and without the new inserts throughout the hospital. Radiofrequency identification tags were used with special software to monitor blood cooler tracking. An educational policy on how to handle the coolers was initiated. Data were gathered from the software that provided a real-time location monitoring of the blood coolers with inserts throughout the institution. The implementation of the blood cooler with inserts and tracking device reduced mean yearly RBC wastage by fourfold from 0.64% to 0.17% between 2010 and 2015. The conserved RBCs corresponded to a total cost savings of $167,844 during the 3-year postimplementation period. The implementation of new blood cooler inserts, tracking system, and educational initiatives substantially reduced the mean annual total RBC wastage. The cost to implement this initiative may be small if there is an existing institutional infrastructure to monitor and track hospital equipment into which the blood bank intervention can be adapted when compared to the cost of blood wastage.


DNA polymorphism at the casein loci in sheep.
By using seven endonucleases and four bovine cDNA probes specific for alpha S1-, alpha S2-, beta-, and kappa-casein genes, nine restriction fragment length polymorphisms (RFLPs) have been found in the sheep orthologous DNA regions. In contrast to the low level of variation observed at the protein level, these DNA polymorphisms determine a high level of heterozygosity and, therefore, represent useful tools for genetic analyses since they can also be obtained without the need for gene expression. In fact, informative matings suggest that in sheep, as in cattle, the four loci are linked.


[Longitudinal epiphyseal bracket of the first metatarsus (delta bone)].
The longitudinal epiphyseal bracket (LEB) or delta bone is a rare congenital ossification anomaly generally observed in finger or toe phalanges but occasionally in the metatarsus or metacarpus. LEB is initially composed of cartilage forming a bracket linking the proximal and distal epiphyses and causing defective growth of the primary ossification focus. Changes in bone growth secondary to the presence of a LEB would be the cause the angle malformations and length discrepancies observed in these subjects. This raises significant therapeutic problems and repeated surgical interventions when the diagnosis is not established early enough. The clinical presentation of LEB of the first metatarsus is similar to metatarsus adductus or hallux varus primus. The particular aspect on the plain x-ray enables the diagnosis. We operated five feet presenting LEB of the first metatarsus in three children aged on average 23 months (range 8 months to 3 years 10 months). The cartilage bracket was removed, followed by metatarso-phalangeal centromedullary pinning. We studied the course of the angle and length deformities and report outcome at mean follow-up of 4 years 11 months (range 2 years to 3 years 10 months). Clinical improvement with correction of the angle deformities was observed in all feet. The length discrepancies did not resolve completely. The degree of correction depended on the age at the time of surgery. In light of the results obtained in this series and considering the negative prognosis of late surgical management, it would be advisable to obtain a plain x-ray of the foot in all children presenting metatarsus adductus associated with a short first ray.


New roles for "old" microRNAs in nervous system function and disease.
Since their discovery, microRNAs became prominent candidates providing missing links on how to explain the developmental and phenotypical variation within one species or among different species. In addition, microRNAs were implicated in diseases such as neurodegeneration and cancer. More recently, the regulation of animal behavior was shown to be influenced by microRNAs. In spite of their numerous functions, only a few microRNAs were discovered by using classic genetic approaches. Due to the very mild or redundant phenotypes of most microRNAs or their genomic location within introns of other genes many regulatory microRNAs were missed. In this review, we focus on three microRNAs first identified in a forward genetic screen in invertebrates for their essential function in animal development, namely bantam, let-7, and miR-279. All three are essential for survival, are not located in introns of other genes, and are highly conserved among species. We highlight their important functions in the nervous system and discuss their emerging roles, especially during nervous system disease and behavior.


Interior Melting of Rapidly Heated Gold Nanoparticles.
Normal melting invariably starts from surfaces or interfaces due to the weaker bonding constraints in these regions. However, we show that melting can be initiated from the interior of gold nanoparticles with high heating rates. We find that melting starts from the surface with the formation of a premelting layer, as usual, but that the premelting layer does not extend to the interior under certain conditions. Instead, liquid nucleation occurs in the core of the nanoparticle. This unexpected interior melting is connected to the slower melting kinetics, which is related to heat transfer near the premelted surface. The required conditions for interior melting are a suitable size of the nanoparticle and a sufficiently fast heating rate. The present results point to a novel melting regime in nanoparticles. We note that the time scales are now accessible using ultrafast tools such as X-ray lasers that can probe dynamical structure changes, suggesting opportunities for experiments.


[Impact of kidney biopsy on the management of patients in the rheumatology department: retrospective study].
Kidney involvement is a common manifestation of the systemic autoimmune rheumatic diseases. Kidney biopsy is the gold standard for the diagnosis of kidney diseases, however this method has not yet become the standard-of-care in rheumatology practice. To assess the diagnostic value of kidney biopsy in the management of patients of the rheumatology department. In this retrospective observational study we analyzed the medical documentation including kidney morphology findings in the patients of the Department of Rheumatology at Tareev Clinic of Internal Diseases. All patients included in the research had signs of kidney involvement and had undergone needle biopsy of the kidney or re-evaluation of the kidney tissue received previously. From June 2016 to October 2021, 3110 patients were admitted to the rheumatology department. Among them 63 (2%) underwent kidney biopsy and were included in the study. Twenty (32%) were male. Mean age was 42.513.9 years. The most common preliminary diagnoses before kidney biopsy were ANCA-associated vasculitis (n=17), systemic lupus erythematosus (n=12), and AA-amyloidosis associated with inflammatory joint diseases (n=7). In 14 (27%) patients diagnosis was unspecified at the time of biopsy. Among 49 patients with established preliminary diagnosis morphological findings were in line 38 (78%) with the pre-liminary diagnosis. However, in 11 (22%) patients morphological findings resulted in the change of the diagnosis. In all 14 patients with unspecified condition kidney biopsy helped to establish clinical diagnosis. Ultrasound evaluation demonstrated hematoma formation in 18 (31%) patients, and among them two required blood component transfusions. Our study demonstrates significant value and safety of kidney biopsy in the patients with autoimmune rheumatic conditions. We suggest that kidney biopsy should be implemented in the management of this category of patients.


Substance P prevents 1-methyl-4-phenylpyridinium-induced cytotoxicity through inhibition of apoptosis via neurokinin-1 receptors in MES23.5 cells.
[Sar9, Met(O2)11] termed Substance P (SP), is an effective and selective agonist for the neurokinin‑1 (NK‑1) receptors, which are synthetic peptides, similar in structure to SP. SP is an important neurotransmitter or neuromodulator mediated by neurokinin receptors, namely the SP receptor in the central nervous system. The excitatory effects induced by SP may be selectively inhibited by a neurokinin‑1 receptor antagonist, such as SR140333B. It has been proposed that Parkinson's disease (PD) is primarily caused by the loss of trophic peptidergic neurotransmitter, possibly SP, which may lead to the degeneration of neurons. In previous studies, 1‑methyl‑4‑phenylpyridinium (MPP+) has been frequently utilized to establish animal or cell models of PD. In the present study, to further investigate the effects of SP in PD, MPP+ was employed to investigate the promising anti‑apoptotic effects of SP, and examine the underlying mechanisms of the pathology in the MES23.5 dopaminergic cell line. The results indicated that MPP+‑triggered apoptosis was prevented by treatment with SP. SP treatment also decreased the MPP+‑triggered Ca2+ influx, caspase‑3 re‑activity, reactive oxygen species production and mitochondrial membrane potential decrease. Treatment with MPP+ also induced phosphorylation of c‑Jun N‑terminal kinase and p38 mitogen‑activated protein kinase. In addition, treatment with SP inhibited the MPP+‑triggered neurotoxicity in MES23.5 cells. However, no changes were observed in SR140333B+SP+MPP+‑treated MES23.5 cell lines. In conclusion, SP could protect the cells from MPP+‑induced cytotoxicity by inhibiting the apoptosis via NK-1 receptors.


Photoactivatable Sensors for Detecting Mobile Zinc.
Fluorescent sensors for mobile zinc are valuable for studying complex biological systems. Because these sensors typically bind zinc rapidly and tightly, there has been little temporal control over the activity of the probe after its application to a sample. The ability to control the activity of a zinc sensor in vivo during imaging experiments would greatly improve the time resolution of the measurement. Here, we describe photoactivatable zinc sensors that can be triggered with short pulses of UV light. These probes are prepared by functionalizing a zinc sensor with protecting groups that render the probe insensitive to metal ions. Photoinduced removal of the protecting groups restores the binding site, allowing for zinc-responsive changes in fluorescence that can be observed in live cells and tissues.


Kyphosis correction and height restoration effects of percutaneous vertebroplasty.
Percutaneous vertebroplasty is known for its pain-relieving effect. Our purpose was to evaluate its effect on the kyphosis angle, wedge angle, and height of the fractured vertebral body. We reviewed digital radiographs of 73 vertebral bodies in 53 patients before and after vertebroplasty. We measured the spinal kyphosis angle and the wedge angle of the fractured vertebral body. Ratios of the height of the anterior border, center, and posterior borders of the collapsed vertebra to the height at the posterior border of an adjacent normal vertebral body were measured. Gain from vertebroplasty and the restoration percentage (gain divided by loss) were calculated for each parameter. The kyphosis angle, wedge angle, anterior height, center height, and posterior height significantly improved after vertebroplasty. The mean reduction in the kyphosis angle was 4.3 degrees, and the wedge-angle reduction was 7.4 degrees. The mean wedge-angle reduction in fractured vertebral bodies containing gas was 10.2 degrees. Restoration percentages for the kyphosis angle and wedge angle were 19% and 44%, respectively. Gain in the height of the fractured vertebral bodies was 16.7% for the anterior border, 14% for the center, and 7% for the posterior border. Restoration percentages for the height of the vertebral body were 29% for the anterior border and 27% for the center. Vertebroplasty increases the height of the fractured vertebra and reduces the wedge and kyphosis angles. These effects are most remarkable in fractured vertebra containing gas.


Correlation between long-term aspirin use and F-fluorodeoxyglucose uptake in colorectal cancer measured by PET/CT.
The aim of this study was to evaluate the relationship between long-term aspirin use with pretreatment 18 Fluorodeoxyglucose (FDG) uptake of primary lesions of Colorectal cancer (CRC) and evaluate their clinical significance. We enrolled 84 patients with CRC who underwent 18F-FDG PET/CT scanning before surgery between 1st July 2008 and 1st March 2013 and followed up until 1st March 2014. Maximum standardized uptake value (SUVmax) of the primary tumor was measured by 18F-FDG PET/CT. The history of aspirin taken and other clinicopathogical factors were also obtained and their relationships were examined by Mann-Whitney or χ2 tests. Progression-free survival (PFS) was determined by standard Kaplan-Meier survival analysis. Cox proportional hazards regression was performed to determine whether history of aspirin taken, pretreatment SUVmax, age, gender, TNM stage, tumor sizes and differentiation influenced outcomes. CRC Patients with long-term history of aspirin use had lower SUVmax of primary lesions than control group (9.74±2.62 vs. 13.91±6.18) and showed a trend towards improved PFS after curative surgery. However, pretreatment of SUVmax showed no prognostic value in patients with CRC. Long-term aspirin use is associated with lower pretreatment SUVmax of CRC and is a promising prognostic factor for predicting PFS in patients with CRC.


Fetal control of parturition in marsupials.
Among marsupials, the control of birth is best understood in the tammar wallaby. The young is tiny relative to the mother and is highly altricial. Adult female tammar wallabies weigh 5 kg, whereas the neonate weighs about 400 mg. However, despite this small size, there is clear evidence that the fetus provides the signal that sets the timing of birth through several mechanisms. A fetal signal activates a nitric oxide-guanylate cyclase system in the myometrium that may maintain myometrial inactivity, and this is down-regulated at term. There is also up-regulation of prostaglandin (PG) production in the gravid endometrium during the last two days of gestation that parallels increased placental PG synthesis, and a pregnancy-specific up-regulation of oxytocin receptors in the gravid myometrium that increases the responsiveness of the gravid uterus to mesotocin. These changes facilitate parturition, but an acute fetus-derived signal appears to trigger parturition. The fetal signal is probably related to glucocorticoid production. The fetal adrenal matures and is able to synthesize cortisol by Day 22 of the 26-day gestation. The fetal adrenals double in size between Day 24 and term, and their cortisol content increases over 10-fold. The pituitary of the neonate contains presumptive corticotrophs, and the adrenals increase cortisol production in response to adrenocorticotrophin. Prostaglandin E2, which is produced by the placenta, is also a potent stimulant of fetal adrenal cortisol synthesis. Treatment of tammars in late gestation with the cortisol agonist, dexamethasone, triggers birth around 23 h later. There is thus a strong case that fetal adrenal cortisol plays a key role in the preparation for birth and the timing of it. Further studies are in progress to more clearly define the mechanisms behind these actions of cortisol.


How solid-liquid adhesive property regulates liquid slippage on solid surfaces?
The influence of solid-liquid adhesive property on liquid slippage at solid surfaces has been investigated using experiment approach on well-defined model surfaces as well as theoretical analysis. Based on a classical molecular-kinetic description for molecular and hydrodynamic slip, we propose a simple theoretical model that directly relates the liquid slip length to the liquid adhesive force on solid surfaces, which yields an exponential decay function. Well-defined smooth surfaces with varied surface wettability/adhesion are fabricated by forming self-assembled monolayers on gold with different mole ratios of hydrophobic and hydrophilic thiols. The adhesive force of a water droplet and the molecular slippage on these surfaces are probed by surface force apparatus and quartz crystal microbalance measurements, respectively. The experiment results are well consistent with our theoretical prediction. Our finding benefits the understanding of the underlying mechanism of liquid slippage on solid surfaces at molecular level and the rational design of microfluidics with an aim to be frictionless or highly controllable.


Endothelium in the pathogenesis of main vascular diseases.
An attempt was made to show that a special methodology based on functional in vivo aspects (induction of increased enothelemia by suitable challenges) may help to obtain an integrated and potentially useful new look at both the pathogenesis and therapy of thrombosis and atherosclerosis.


Tec protein-tyrosine kinase directly associates with Lyn protein-tyrosine kinase through its N-terminal unique domain.
Most of non-receptor-type protein-tyrosine kinases share common structures, such as N-terminal unique domains, Src homology region (SH)-2 domains, SH-3 domains and kinase domains. Although vast effort has brought some information about the in vivo roles of SH-2, -3 and kinase domains, little is still understood about the function of N-terminal unique domain. By utilizing the glutathione S-transferase (GST)-fusion system, we have investigated the role of N-terminal unique domain of the Tec protein-tyrosine kinase in a mouse IL-3-dependent myeloid cell line. We could reveal that the C-terminal half of the Tec N-terminal unique domain (NTec2 region) can bind to a set of tyrosine-phosphorylated cellular proteins in vitro in an IL-3-dependent manner. Surprisingly, p56/53Lyn constitutively binds to the NTec2 region. Among the NTec2-bound Lyn proteins, only the p56 form seems to be inducibly tyrosine-phosphorylated in response to IL-3. Binding domain of Lyn to the NTec2 region was localized to its SH-3 domain. Tec was also shown to make a stable complex with Lyn in vivo. This is the first report demonstrating the direct association between distinct cytoplasmic protein-tyrosine kinases, especially through N-terminal unique domain.


[Important role of a nurse parctitioner-like specialized registered nurse in a cardiac surgery team].
Team medical practice by physician, nurse, and other co-medical staffs has been performed and it provides numerous values to the patients. Japanese Ministry of Health, Labor and Welfare reported that a registered nurse was a key person of medicine. The importance of nurse's role expansion and involving medical cure by a registered nurse was emphasized in the report. Japanese nurse practitioner for a new profession is going to start in near future. In our institute, a specialized registered nurse has joined a cardiac surgery team. She plays an important role of assisting and consulting cardiac physicians for patient cure and care as a member of the surgery team. Cardiac surgery team including specialized registered nurse gives quality surgical results and patient satisfaction.


Protective effects of 3-alkyl luteolin derivatives are mediated by Nrf2 transcriptional activity and decreased oxidative stress in Huntington's disease mouse striatal cells.
Huntington's disease (HD) is a polyglutamine-expansion neurodegenerative disorder caused by increased number of CAG repeats in the HTT gene, encoding for the huntingtin protein. The mutation is linked to several intracellular mechanisms, including oxidative stress. Flavones are compounds with a protective role in neurodegenerative pathologies. In the present study we analyzed the protective effect of luteolin (Lut, 3',4',5,7-tetrahydroxyflavone) and four luteolin derivatives bearing 3-alkyl chains of 1, 4, 6 and 10 carbons (Lut-C1, Lut-C4, Lut-C6, Lut-C10) in striatal cells derived from HD knock-in mice expressing mutant Htt (STHdh(Q111/Q111)) versus wild-type striatal cells (STHdh(Q7/Q7)). HD cells showed increased caspase-3-like activity and intracellular reactive oxygen species (ROS), which were significantly decreased following treatment with Lut-C4 and Lut-C6 under concentrations that enhanced cell viability. Interestingly, Lut-C4 and Lut-C6 rose the nuclear levels of phospho(Ser40)-nuclear factor (erythroid-derived-2)-like 2 (Nrf2) and Nrf2/ARE transcriptional activity. Concordantly with increased Nrf2/ARE transcription, Lut-C6 enhanced superoxide dismutase 1 (SOD1) mRNA and SOD activity and glutamate-cysteine ligase catalytic subunit (GCLc) mRNA and protein levels, while Lut-C4 induced mRNA levels of GCLc only in mutant striatal cells. Data suggest that Lut-C6 luteolin derivative (in particular) might be relevant for the development of antioxidant strategies in HD.


The recovery efficiency of various materials for sampling enzymes and polymorphonuclear leukocytes from gingival crevices.
The present investigation was designed to assess the effects of strips made of different materials on the recovery of enzymes in gingival crevicular fluid (GCF) (Experiment 1), and to examine a possible relationship between lysosomal enzyme activities and number of crevicular polymorphonuclear leukocytes (PMNs) (Experiment 2). In Experiment 1, GCF was collected with capillaries from 14 patients with periodontal disease, and applied on various test strips in microcentrifuged tubes or directly into tubes (controls). Strips were then shaken and centrifuged to elute GCF enzymes. The supernate was used for determinations of alkaline phosphatase (ALP), beta-glucuronidase (BG) and aspartate aminotransferase (AST) activities. The % recoveries were calculated as relative percentages to controls. When using saline as eluent, 90% or more ALP, BG and AST were found to be recovered from strips of durapore and papers. More than 35% of ALP and BG was found to remain on paper points. However, the % recoveries from paper points were improved using eluent with 0.1% (w/v) cetyl pyridinium chloride. In Experiment 2, 54 GCF samples were collected from 3 periodontitis patients by using durapore strips, in order to measure both PMN numbers and BG activities in the same samples. The 2 parameters showed strong and positive correlation with 0.847 (p < 0.001) of the Pearson's correlation coefficient. These findings suggest that durapore is a useful material not only for counting PMNs but also for measuring activities of GCF enzymes. Elevation of BG activities in GCF can be due to increasing numbers of PMNs.


Determinants of health and disability in ageing population: the COURAGE in Europe Project (collaborative research on ageing in Europe).
COURAGE in Europe was a 3-year project involving 12 partners from four European countries and the World Health Organization. It was inspired by the pressing need to integrate international studies on disability and ageing in light of an innovative perspective based on a validated data-collection protocol. COURAGE in Europe Project collected data on the determinants of health and disability in an ageing population, with specific tools for the evaluation of the role of the built environment and social networks on health, disability, quality of life and well-being. The main survey was conducted by partners in Finland, Poland and Spain where the survey has been administered to a sample of 10,800 persons, which was completed in March 2012. The newly developed and validated COURAGE Protocol for Ageing Studies has proven to be a valid tool for collecting comparable data in ageing population, and the COURAGE in Europe Project has created valid and reliable scientific evidence, demonstrating cross-country comparability, for disability and ageing research and policy development. It is therefore recommended that future studies exploring determinants of health and disability in ageing use the COURAGE-derived methodology. COURAGE in Europe Project collected data on the determinants of health and disability in an ageing population, with specific tools for the evaluation of the role of built environment and social networks on health, disability quality of life and well-being. The COURAGE Protocol for Ageing Studies has proven to be a valid tool for collecting comparable data in the ageing population. The COURAGE in Europe Consortium recommends that future studies exploring determinants of health and disability in ageing use COURAGE-derived methodology.


Neuroscience in its context. Neuroscience and psychology in the work of Wilhelm Wundt.
Wilhelm Wundt (1832-1920), the first to establish an Institute devoted exclusively to psychological research in Germany, started his career as a (neuro)physiologist. He gradually turned into a psychologist in the 1860's and 1870's, at a time when neuroscience had to deal with the problem of giving an adequate physiological interpretation of the data accumulated by neuroanatomy. Neither the functional interpretation of brain morphology, nor the options provided by the reflex model seemed acceptable to Wundt. In his Physiological Psychology, first published in 1874, Wundt adds another aspect to this discussion by showing that psychology may help, and indeed is required, to clarify some of the most controversial problems in brain research. He thus became a key figure in neuroscience's struggle to locate itself within the various research traditions. The following theses will be argued for: 1. Wundt's turn to psychology resulted from his view that the methodological basis of physiological brain research of the time was unsatisfactory. 2. Psychology, in its attempt to solve these problems, implied a new conception of an interaction between experimental and theoretical brain research. 3. Wundt tried to demonstrate the necessity of psychological considerations for experimental brain research. These points are discussed with reference to Wundt's treatment of the localization of functions in the brain. According to Wundt, psychology can show, by analyzing the complex structure of intellect and will, that mental phenomena can be realized in the brain only in the form of complex interations of the elements of the brain. The results of the psychological considerations imply that a strict localizations cannot be correct; but they are also turned against the conception of a complete functional equivalence of the various parts of the cortext. For Wundt, a reconstruction of brain processes cannot start with neurones, but only with patterns of a functional organization of brain activity. Wundt accordingly proposes a functional interpretation on the level of the physiology of nervous tissue as well as for the over-all organization of the brain.


Needle Insertion Difficulty Algorithm (NIDA): A novel pilot study to predict Huber needle insertion difficulty in totally implanted devices.
Safeguarding of venous assets in cancer patients provides for positioning vascular devices. In totally implanted central venous access devices, hereinafter referred as TIVADs, it's necessary introducing Huber needle, into subcutaneous port, to use it. This procedure is not easy for all implanted devices. The procedural difficulty is to be attributed both to the type of the implanted port and to the skill of the clinician. The degree of patient satisfaction is variable and related with the clinician performing the maneuver. It follows a professional dissatisfaction of the clinician and a hesitation of the patient. Moreover, the incorrect positioning of the Huber needle into the port, could lead to the infusion of antiblastic drugs into the subcutaneous tissue with the consequent tissue damage due to extravasation of the drugs. Evaluation of different characteristics of TIVADs, allowed grouping them, in different types, setting up the S.P.I.A. method (Subcutaneous Port Investigator Assessment). Collected data from medical records concerning: primary pathology, port's permanence and using, Huber needle insertion failed events, if a vascular access expert/specialist clinician has been called, weight gain or loss were recruited. These data made it possible to determine the types of implanted ports that were most difficult to insert the Huber needle, creating the N.I.D.A. (Needle Inserting Difficulty Algorithm) as a prognostic index of Huber needle inserting into the port. In particular, the type of implanted port, that is, if it was a brachial or thoracic implant (p < 0.001), the SPIA type, if type 1, 2, or 3 (p < 0.001) and the experience of the clinician (p < 0.001) were considered as predictors of a successful first attempt and then can perform the NIDA. The relevant aspects in the success of the procedure are therefore the type of port (thoracic or brachial), the SPIA type, and the experience of the clinician in the successful insertion of the Huber needle into the port at the first attempt.


Traditional criteria as predictors of minority student success in medical school.
There have been many reports stating that the traditional criteria of the Medical College Admission Test (MCAT) and undergraduate grade-point average (GPA) have little, if any, value in predicting success in the preclinical years of medical school among students from underrepresented (racial and ethnic) minority groups. In contrast to previous articles this report emphasizes that traditional criteria and the quality of the undergraduate college attended are of some statistical value in predicting success in the preclinical years of medical school among accepted students from under represented minority groups. Of these criteria, the one with the greatest predictive value is the selectivity of the undergraduate college attended.


No Association between Depression and Risk of Hepatocellular Carcinoma in Older People in Taiwan.
Objectives. The objective of this study was to determine whether there is a relationship between depression and risk of hepatocellular carcinoma (HCC) in older people in Taiwan. Methods. A case-control study was conducted to analyze the database from the Taiwan National Health Insurance program. We selected 1815 subjects aged 65 years or older with newly diagnosed HCC as the case group and 7260 subjects without HCC as the comparison group, from 2000 to 2010. Both groups were compared to measure the risk of HCC. Results. After controlling for confounders, the odds ratio of HCC was 0.81 in subjects with depression (95% confidence interval = 0.59, 1.11), as compared with nondepressed subjects. Conclusions. We conclude that no association is detected between depression and risk of hepatocellular carcinoma in older people in Taiwan.


Renal cell carcinoma of extraordinarily large size: a case report.
One of our patients was a 66-year-old woman with a T2 renal cell carcinoma weighing 3900 g. Two years after radical nephrectomy the woman was alive and well. A survey of Japanese medical literature revealed that patients with renal cell carcinomas weighing more than 2000 g have an unexpectedly favorable prognosis with a 5-year survival rate of 76.9%.


Biochemistry of the tale transcription factors PREP, MEIS, and PBX in vertebrates.
TALE (three amino acids loop extension) homeodomain transcription factors are required in various steps of embryo development, in many adult physiological functions, and are involved in important pathologies. This review focuses on the PREP, MEIS, and PBX sub-families of TALE factors and aims at giving information on their biochemical properties, i.e., structure, interactors, and interaction surfaces. Members of the three sets of protein form dimers in which the common partner is PBX but they can also directly interact with other proteins forming higher-order complexes, in particular HOX. Finally, recent advances in determining the genome-wide DNA-binding sites of PREP1, MEIS1, and PBX1, and their partial correspondence with the binding sites of some HOX proteins, are reviewed. These studies have generated a few general rules that can be applied to all members of the three gene families. PREP and MEIS recognize slightly different consensus sequences: PREP prefers to bind to promoters and to have PBX as a DNA-binding partner; MEIS prefers HOX as partner, and both PREP and MEIS drive PBX to their own binding sites. This outlines the clear individuality of the PREP and MEIS proteins, the former mostly devoted to basic cellular functions, the latter more to developmental functions.


Highly porous carbon nanofiber electrodes for vanadium redox flow batteries.
The electrochemical performance of carbon nanofiber (CNF) electrodes in vanadium redox flow batteries (VRFBs) is enhanced by optimizing the morphological and physical properties of low-cost electrospun CNFs. The surface area, porosity and electrical conductivity of CNFs are tailored by modifying the precursor composition, especially the sacrificing agent, Fe(acac)3, in the polymer precursor and carbonization temperature. A highly porous structure with a large surface area is generated by the catalytic growth of graphitic carbon spheres surrounding the iron nanoparticles which are removed by an acid etching process. The graphitic carbon layers formed at a high carbonization temperature improve the electrical conductivity of CNFs. The large surface area of 349 m2 g-1 together with the abundant mesopore-dominant structure leads to high wettability and high activity for redox reactions of the electrode, giving rise to enhanced electrochemical performance in VRFBs. It delivers an energy efficiency (EE) of 91.4% at a current density of 20 mA cm-2 and 79.3% at 100 mA cm-2, and maintains an average EE of 72.5% after 500 charge/discharge cycles at 100 mA cm-2.


Analysis of cultured keratinocytes from a transgenic mouse model of psoriasis: effects of suprabasal integrin expression on keratinocyte adhesion, proliferation and terminal differentiation.
Many important transgenic mouse models of benign and neoplastic skin diseases have been generated through the use of promoters that target transgene expression to the different epidermal layers. However, more mechanistic studies of the specific effects of the transgenes on keratinocytes have been hampered by difficulties in culturing keratinocytes from adult mouse epidermis and by the low differentiation potential of many established mouse keratinocyte lines. We have used the Rheinwald & Green technique to cultivate primary adult keratinocytes and to generate keratinocyte lines from transgenic mice which have a sporadic psoriatic phenotype due to expression of human integrin subunits under the control of the involucrin promoter. We show that the transgenes are induced when keratinocytes are placed in suspension and that the transgenic integrins are capable of clustering in focal adhesions and mediating cell adhesion and spreading. We also show that suprabasal integrin expression has no direct effect on proliferation of cells in the underlying basal layer, ruling this out as a possible explanation for the epidermal hyperproliferation observed in the transgenic mice.


Prognostic Value of Post First-Line Chemotherapy Glasgow Prognostic Score in Advanced Non-Small Cell Lung Cancer.
The Glasgow prognostic score (GPS) is an established inflammatory prognostic index in cancer patients. Most studies have only measured GPS at baseline (B-GPS). Effective cancer therapy may reduce inflammation, and we investigated whether re-assessing GPS after first-line chemotherapy (E-GPS) provided more prognostic information than B-GPS in a phase III trial of advanced non-squamous non-small cell lung cancer (NSCLC). Glasgow prognostic score was assessed before and after carboplatin/vinorelbine chemotherapy. When assessing GPS, C-reactive protein (CRP) ⩾ 10 mg/L and albumin < 35 mg/L are defined as abnormal values. GPS 0: both values normal, GPS 1: one abnormal value, and GPS 2: both values abnormal. Glasgow prognostic score at baseline and E-GPS were available in 138 patients. Median age was 67 years, 51% were women, and 94% had performance status 0-1. B-GPS was not a statistically significant prognostic factor (B-GPS 1 vs 0: hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.9-2.0; B-GPS 2 vs 0: HR = 1.46, 95% CI = 0.9-2.3), while E-GPS was (E-GPS 1 vs 0: HR = 1.57, 95% CI = 1.0-2.4; E-GPS 2 vs 0: HR = 2.77, 95% CI = 1.7-4.5). E-GPS was associated with treatment response (P < .01), whereas B-GPS was not. Glasgow prognostic score at baseline after first-line chemotherapy provided more prognostic information than baseline GPS in patients with advanced non-squamous NSCLC and was associated with treatment response. NCT02004184.


Inhibitory action of chemically deglycosylated human chorionic gonadotrophin on hormone-induced steroid production by dispersed cells from human corpus luteum.
The biological activity of deglycosylated human chorionic gonadotrophin (hCG) prepared by treatment of the native hormone with anhydrous hydrogen fluoride was evaluated using suspensions of dispersed cells from biopsies of human corpus luteum obtained during the luteal phase of normal menstrual cycles. A reproducible pattern of response to hCG in terms of progesterone production by luteal cells was established for a range of luteal ages. Deglycosylation of hCG led to a diminished level of maximum response to the hormone. Co-incubation of luteal cells with a level of hCG just sufficient to elicit a maximum response and increasing concentrations of deglycosylated hCG led to a progressive inhibition of the hormonal response; at a concentration of 10(3) ng deglycosylated hCG/ml (a tenfold excess of deglycosylated hCG over the native hormone), hCG-induced progesterone production was reduced by about 50%. Deglycosylated hCG therefore acts as a partial antagonist for the action of hCG on human luteal cells.


Severe ocular injuries from improperly disposed medical syringes in children.
This report describes ocular injuries caused by syringes in children. The records of 12 children injured with syringes were reviewed. There were seven cases of endophthalmitis, two cases of panophthalmitis, one case of retinal detachment, one case of endophthalmitis with retinal detachment, and one case of traumatic cataract. All patients received treatment within 24 hours of presentation. Patients presented an average of 8.4 days after injury. Final visual acuity ranged from no light perception to counting fingers at 90 cm in eight patients and could not be assessed in four patients. Improperly disposed syringes may pose a significant risk for ocular injury and visual loss in children, especially when presentation is delayed.


Correcting prevalence estimation for biased sampling with testing errors.
Sampling for prevalence estimation of infection is subject to bias by both oversampling of symptomatic individuals and error-prone tests. This results in naïve estimators of prevalence (ie, proportion of observed infected individuals in the sample) that can be very far from the true proportion of infected. In this work, we present a method of prevalence estimation that reduces both the effect of bias due to testing errors and oversampling of symptomatic individuals, eliminating it altogether in some scenarios. Moreover, this procedure considers stratified errors in which tests have different error rate profiles for symptomatic and asymptomatic individuals. This results in easily implementable algorithms, for which code is provided, that produce better prevalence estimates than other methods (in terms of reducing and/or removing bias), as demonstrated by formal results, simulations, and on COVID-19 data from the Israeli Ministry of Health.


Instability growth rates of crossing sea states.
Crossing sea states can occur during adverse weather conditions. The instability of such wave trains has been suggested as a possible mechanism for the formation of rogue (freak or extreme) waves. One model for crossing sea states is weakly nonlinear and finite-amplitude short-crested waves (SCWs) on deep water. SCWs are the resonant interaction of two wave systems each with a different direction of propagation. Recently, it has been shown that the stability of these wave interactions is closely associated with the stability of the oblique nonresonant interaction between two waves. The long-wave instability of such waves is considered here; SCWs are used as a benchmark. By using a mismatch of amplitudes, it is demonstrated that instability growth rates of two crossing waves can be larger than those given by SCWs. This indicates that only considering true resonant interactions can underestimate the contribution from unstable crossing sea states to the possible formation of rogue waves.


IL-10 as an autocrine regulator of CSF secretion by monocytes: disparate effects on GM-CSF and G-CSF secretion.
In previous studies of endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) production, we found several differences in the secretion pattern within and between different cell systems; for example, CSF secretion by endothelial cells is not affected by any major downregulatory factors, whereas monocyte CSF secretion is modulated by several mechanisms. In this study, we characterized the factors that inhibit CSF secretion by monocytes. Three cytokines have inhibitory effects: interleukin (IL)-4, IL-10, and IL-13. Among these, IL-4 and IL-10 have higher potency than IL-13. IL-4 and IL-13 affect GM-CSF and G-CSF secretion to the same extent. In contrast, exogenously added IL-10 has a stronger inhibitory effect on GM-CSF secretion than on G-CSF secretion. We also found that monocytes produce IL-10 with an autocrine downregulatory effect, and that this autocrine IL-10 reaches concentrations at which in most cases only GM-CSF (not G-CSF) secretion is significantly affected. We postulate that the disparate effect of IL-10 on monocyte secretion of the two CSFs reflects their physiological functions, with GM-CSF being mainly a proinflammatory cytokine working in the local compartment and G-CSF functioning mainly as a cell recruiting factor.


Nerve injury after laparoscopic varicocelectomy.
Laparoscopic varicocelectomy is a minimally invasive option for varicoceles in children. Occasional reports of nerve injury after inguinal laparoscopic procedures have been published. There is anatomical variation in the sensory innervation of the anterior thigh and variable branching patterns of the nerves involved. We report a retrospective analysis of our patients, focusing on the incidence of sensory changes on the ipsilateral anterior thigh after laparoscopic varicocelectomy. The medical records of all patients who underwent laparoscopic varicocelectomy at 1 institution performed by 2 of us (YR and DV) from 1997 to 2002 were retrospectively reviewed. Demographics, outcomes and any postoperative sensory complications were obtained by chart review and telephone interview. A total of 58 patients underwent laparoscopic varicocelectomy during this 5-year analysis and 51 with a total of 62 varicoceles were available for review. Three patients (4.8%) experienced transient numbness of the ipsilateral anterior thigh, which resolved or improved in an average of 8.0 months (range 6 to 9). Symptoms were not always noticed immediately postoperatively (range 0 to 10 days). In affected patients the sensory distribution was usually consistent with injury to the genitofemoral nerve. Laparoscopic varicocelectomy is a minimally invasive procedure that still has the potential for complications. Cautery or harmonic dissection of the peritoneum overlying the spermatic cord and excessive traction on the tissues surrounding the cord should be avoided intraoperatively. Patients and surgeons should be aware of the possibility of nerve injury and the resultant sensory deficit.


Parahydrogen-Induced Polarization Relayed via Proton Exchange.
The hyperpolarization of nuclear spins is a game-changing technology that enables hitherto inaccessible applications for magnetic resonance in chemistry and biomedicine. Despite significant advances and discoveries in the past, however, the quest to establish efficient and effective hyperpolarization methods continues. Here, we describe a new method that combines the advantages of direct parahydrogenation, high polarization (P), fast reaction, and low cost with the broad applicability of polarization transfer via proton exchange. We identified the system propargyl alcohol + pH2 → allyl alcohol to yield 1H polarization in excess of P ≈ 13% by using only 50% enriched pH2 at a pressure of ≈1 bar. The polarization was then successfully relayed via proton exchange from allyl alcohol to various target molecules. The polarizations of water and alcohols (as target molecules) approached P ≈ 1% even at high molar concentrations of 100 mM. Lactate, glucose, and pyruvic acid were also polarized, but to a lesser extent. Several potential improvements of the methodology are discussed. Thus, the parahydrogen-induced hyperpolarization relayed via proton exchange (PHIP-X) is a promising approach to polarize numerous molecules which participate in proton exchange and support new applications for magnetic resonance.


Field application of serodiagnostics to identify elephants with tuberculosis prior to case confirmation by culture.
Three serologic methods for antibody detection in elephant tuberculosis (TB), the multiantigen print immunoassay (MAPIA), ElephantTB STAT-PAK kit, and DPP VetTB test, were evaluated using serial serum samples from 14 captive elephants infected with Mycobacterium tuberculosis in 5 countries. In all cases, serological testing was performed prior to the diagnosis of TB by mycobacterial culture of trunk wash or tissue samples collected at necropsy. All elephants produced antibody responses to M. tuberculosis antigens, with 13/14 recognizing ESAT-6 and/or CFP10 proteins. The findings supported the high serodiagnostic test accuracy in detecting infections months to years before M. tuberculosis could be isolated from elephants. The MAPIA and/or DPP VetTB assay demonstrated the potential for monitoring antimycobacterial therapy and predicting TB relapse in treated elephants when continuously used in the posttreatment period. History of exposure to TB and past treatment information should be taken into consideration for proper interpretation of the antibody test results. Data suggest that the more frequent trunk wash culture testing of seropositive elephants may enhance the efficiency of the TB diagnostic algorithm, leading to earlier treatment with improved outcomes.


Lanthanide-MOFs as multi-responsive photoluminescence sensor for sensitively detecting Fe3+, Cr2O72- and nitrofuran antibiotics.
Fast and selective detection of contaminants plays a key role in meeting human health and environmental concerns. Herein, two groups of isostructural lanthanide MOFs, [Ln(Hpta)(oxalic acid)]·H2O (1-Eu, 2-Gd) and [Ln(pta)(oxalic acid)0.5(H2O)2]·2H2O (3-Eu, 4-Gd) (H2pta = 2-(4-pyridyl)-terephthalic acid, C2O4- = oxalic acid), were synthesized by solvothermal method. Single crystal X-ray diffraction reveals that 1 and 2 are 3D neutral frameworks, while 3 and 4 consist of 2D layers with parallelogram holes and stack into 3D networks through O-H⋯N and O-H⋯O hydrogen bonding interactions. All complexes remain crystalline and stable below 400 °C, suggesting preeminent thermostability. Noteworthily, only 3 shows excellent chemical stability in water and organic solvent. Therefore, the solid-state fluorescence spectrum was used to characterize 3 which exhibited intense red luminescence. The N active sites in the pore channels of 3 are conducive to displaying a distinct quenching effect for Fe3+ cations in aqueous solutions, Cr2O72- anions in DMF and DMA solutions, and nitrofuran antibiotics in the DMF solvent. Overall, 3 is a prospective luminescent sensor for detecting Fe3+, Cr2O72- and nitrofuran antibiotics.


Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules.
The ability of murine NK cells to reject cells lacking self MHC class I expression results from an in vivo education process. To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (K(b), D(b), D(d), or L(d)) or combinations of two or more alleles. All single MHC class I mice rejected MHC class I-deficient cells in an NK cell-dependent way. Expression of K(b) or D(d) conveyed strong rejection of MHC class I-deficient cells, whereas the expression of D(b) or L(d) resulted in weaker responses. The educating impact of weak ligands (D(b) and L(d)) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (K(b) and D(d)) maintained their educating impact under such conditions. An analysis of activating and inhibitory receptors in single MHC class I mice suggested that the educating impact of a given MHC class I molecule was controlled both by the number of NK cells affected and by the strength of each MHC class I-Ly49 receptor interaction, indicating that NK cell education may be regulated by a combination of qualitative and quantitative events.


Reaction pathways involved in the mechanism of AlIII chelation with caffeic acid: catechol and carboxylic functions competition.
Density functional theory calculations on the AlIII-caffeic acid system are carried out to investigate the fixing mechanism of this metal ion to the two competing complexing sites in the ligand. This theoretical study was performed to explain the complex formation of 1:1 stoichiometry observed in aqueous medium at low pH values. Both complexation with the catechol and carboxylic functions are envisaged. The reaction pathways for the formation of these two chelates are calculated at the B3LYP/6-31G** level of theory. The complexation on the more acidic group is relatively straightforward and shows the intermediate formation of a monodentate complex followed by a chelation process. The complexation reaction pathway with the catechol function is more sophisticated, and several pathways are explored. Once more, the formation of a monodentate complex is achieved and the most favorable pathway for chelation involves the successive steps: 1) coordination of AlIII on the oxygen atom of a hydroxyl group, 2) deprotonation of this hydroxyl group, 3) ring closure with the other oxygen atom, and 4) deprotonation of the second hydroxyl. From an energetic point of view, this second pathway is more favorable. Notably the energy barrier necessary to form the chelate is lower for the catechol function than that calculated for the carboxylic group. The results of this purely theoretical study are in complete agreement with spectroscopic investigations performed on this system.


Correlation of hypertension with waist circumference in Iranian adults.
Cardiovascular disease (CVD) is the most important cause of mortality in developed and developing countries. Hypertension is a major risk factor for CVD. Waist circumference (WC) cut-off point is a simple way to recognize risk of developing hypertension. However, there are different cut-off points for different races, including Iranians. The objective of this article was to determine the association between WC and hypertension as an important cardiovascular risk factor in the Iranian population. A total of 850 subjects (430 women and 420 men) older than 18 years, who were residents in the urban and rural areas throughout Arak city, Iran, were included in the present study. WC of subjects was measured to identify its relationship with hypertension. Fasting plasma glucose and lipid profile were also measured. WC cut-off point to predict hypertension was 89 cm and 93 cm for men and women, respectively, by using receiver operator characteristic curve analysis. The results of our analysis showed that the cut-off point of WC in the Iranian population is greater than other Asians and WC is a strong index to predict hypertension.


Pre-conditions for eliminating mitochondrial dysfunction and maintaining liver function after hepatic ischaemia reperfusion.
The liver, the largest organ with multiple synthesis and secretion functions in mammals, consists of hepatocytes and Kupffer, stem, endothelial, stellate and other parenchymal cells. Because of early and extensive contact with the external environment, hepatic ischaemia reperfusion (IR) may result in mitochondrial dysfunction, autophagy and apoptosis of cells and tissues under various pathological conditions. Because the liver requires a high oxygen supply to maintain normal detoxification and synthesis functions, it is extremely susceptible to ischaemia and subsequent reperfusion with blood. Consequently, hepatic IR leads to acute or chronic liver failure and significantly increases the total rate of morbidity and mortality through multiple regulatory mechanisms. An increasing number of studies indicate that mitochondrial structure and function are impaired after hepatic IR, but that the health of liver tissues or liver grafts can be effectively rescued by attenuation of mitochondrial dysfunction. In this review, we mainly focus on the subsequent therapeutic interventions related to the conservation of mitochondrial function involved in mitigating hepatic IR injury and the potential mechanisms of protection. Because mitochondria are abundant in liver tissue, clarification of the regulatory mechanisms between mitochondrial dysfunction and hepatic IR should shed light on clinical therapies for alleviating hepatic IR-induced injury.


The INMA-INfancia y Medio Ambiente-(Environment and Childhood) project: More than 10 years contributing to environmental and neuropsychological research.
In 2003 the INMA-INfancia y Medio Ambiente (Environment and Childhood) project, a Spanish national network of birth cohorts including more than 3500 participants, was set up with the aim to assess the health impacts of pre- and postnatal environmental exposures on children. The project has published more than 60 papers on maternal and environmental factors related to neuropsychological development in children, one of the main research interests within the project. With the present review, we evaluate the evidence provided by the INMA project on this topic and discuss how the data can contribute to cover the challenges that children's environmental health research will face in the coming years. The INMA project has contributed to provide increasing evidence of the association between prenatal exposure to persistent organic pollutants (POPs) and child neuropsychological development, but it has also shown, using innovative methodologies, that postnatal exposure to these compounds does not play a role in this association. The project has also contributed to show the detrimental influence of certain air pollutants on child neuropsychological development, as well as how a balanced maternal fish intake can protect from the potential adverse effects of prenatal exposure to mercury. Also, the project has contributed to the understanding of impacts of nutritional factors including supplement intake and vitamin D levels during pregnancy and the role of breastfeeding on the neuropsychological benefits. INMA findings underscore the importance of continued research on the delineation of the sensitive windows of exposure both during pregnancy and postnatally and on the combined effects of environmental exposures, denoted the exposome. In terms of health policy, INMA findings have important implications for the development of public health policies to advance the health and development of children.


Silver Vapor Supersonic Jets: Expansion Dynamics, Cluster Formation, and Film Deposition.
Supersonic jets of metal vapors with carrier gas are promising for producing nanostructured metal films at relatively low source temperatures and high deposition rates. However, the effects of the carrier gas on the jet composition and expansion dynamics, as well as on film properties, remain virtually unexplored. In this work, the free-jet expansion of a mixture of silver vapor with helium in a rarefied regime at an initial temperature of 1373 K is investigated through mass spectrometry and direct-simulation Monte Carlo methods. Introducing the carrier gas into the source is found to result in a transition from a collisionless to a collision-dominated expansion regime and dramatic changes in the Ag jet, which becomes denser, faster, and more forward-directed. The changes are shown to be favorable for the formation of small Ag clusters and film deposition. At a fairly high helium flow, silver Ag2 dimers are observed in the jet, both in the experiment and the simulations, with a mole fraction reaching 0.1%. The terminal velocities of silver atoms and dimers are nearly identical, indicating that the clusters are likely formed due to the condensation of silver vapor in the expanding jet. A high potential of supersonic Ag-He jets for the deposition of nanostructured silver films is demonstrated. The deposited jet Ag2 dimers appear to serve as nucleation centers and, thus, allow for controlling the size of the produced surface nanostructures.


[Sodium pegaptanib and ranibizumab in the treatment of the retinal pigment layer ablation in a patient with age-related macular degeneration--a case report].
The case report presents the difference of the effect of two drugs blocking vascular endothelial growing factor (anti-VEGF)--sodium pegaptanib and ranibizumab--in a female patient with the retinal pigment epithelium (RPE) layer ablation as a part of the exsudative age-related macular degeneration. Fifty-five years old female patient with RPE ablation as a sign of exsudative ARMD and central visual acuity 79 letters of the EDTRS chart in the left eye was treated by 5 intravitreal injections of sodium pegaptanib. The treatment was not sufficiently effective according to the fluorescein angiography (FAG) and optic coherence tomography (OCT) findings and was accompanied by further decrease of the visual acuity to 55 letters of the EDTRS chart. After the medication was switched to ranibizumab with 3 intravitreal applications, the RPE ablation flattened according to the OCT findings and the fluorescein leakage during the FAG markedly decreased. The central visual acuity improved to 63 letters of the EDTRS chart. The decreased activity of the choroidal neovascularization (CNV) is observed during the following 4 months after the last intravitreal application of ranibizumab. Ranibizumab seems to be more effective drug comparing to the sodium pegaptanib in patients with the RPE ablation, but it is necessary to consider the increased probability of the RPE rupture risk.


Oral health and treatment needs among patients in psychiatric institutions for the elderly.
The purpose of the study was to assess oral health and treatment needs among elderly in psychiatric institutions in a Danish county. The study serves as baseline for the evaluation of a newly established oral health care program in the county. The study population comprised the residents in eight institutions (n = 407). Two thirds of the residents were edentulous, 34% of the dentate had one or more root remnants, and 55% had untreated decay. The dentate with regular dental visiting habits had significantly less untreated decay than the irregular users. The oral hygiene was poor, but was not related to whether or not the elderly were assisted in daily oral hygiene. The evaluation of the program will show to what extent treatment takes place, and whether or not oral hygiene improves.


In vitro effects on microtubule dynamics of purified Xenopus M phase-activated MAP kinase.
The protein kinase MAP kinase, also called MAP2 kinase, is a serine/threonine kinase whose activation and phosphorylation are induced by a variety of mitogens, and which is thought to have a critical role in a network of protein kinases in mitogenic signal transduction. A burst in kinase activation and protein phosphorylation may also be important in triggering the dramatic reorganization of the cell during the transition from interphase to mitosis. The interphase-metaphase transition of microtubule arrays is under the control of p34cdc2 kinase, a central control element in the G2-M transition of the cell cycle. Here we show that a Xenopus kinase, closely related to the mitogen-activated mammalian MAP kinase, is phosphorylated and activated during M phase of meiotic and mitotic cell cycles, and that the interphase-metaphase transition of microtubule arrays can be induced by the addition of purified Xenopus M phase-activated MAP kinase or mammalian mitogen-activated MAP kinase to interphase extracts in vitro.


Human Intestinal Organoids: Promise and Challenge.
The study of human intestinal biology in healthy and diseased conditions has always been challenging. Primary obstacles have included limited tissue accessibility, inadequate in vitro maintenance and ethical constrains. The development of three-dimensional organoid cultures has transformed this entirely. Intestinal organoids are self-organized three-dimensional structures that partially recapitulate the identity, cell heterogeneity and cell behaviour of the original tissue in vitro. This includes the capacity of stem cells to self-renew, as well as to differentiate towards major intestinal lineages. Therefore, over the past decade, the use of human organoid cultures has been instrumental to model human intestinal development, homeostasis, disease, and regeneration. Intestinal organoids can be derived from pluripotent stem cells (PSC) or from adult somatic intestinal stem cells (ISC). Both types of organoid sources harbour their respective strengths and weaknesses. In this mini review, we describe the applications of human intestinal organoids, discussing the differences, advantages, and disadvantages of PSC-derived and ISC-derived organoids.


Immunotherapy strategies for EGFR-mutated advanced NSCLC after EGFR tyrosine-kinase inhibitors failure.
This study aimed to investigate the efficacy of immunotherapy, as monotherapy or in combination, comparing to chemotherapy with or without anti-angiogenesis for advanced non-small cell lung cancer (NSCLC) patients progressing to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). We retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who received immune checkpoint inhibitors (ICI) and/or chemotherapy after EGFR-TKIs failure at Shanghai Chest Hospital between Aug 2016 and Oct 2022. According to the subsequent immunotherapy regimen, the patients were assigned to ICI monotherapy (IM), IO plus anti-angiogenesis (IA), ICI plus chemotherapy (IC), ICI plus chemotherapy plus anti-angiogenesis (ICA). Eligible patients undergoing standard chemotherapy were assigned to chemotherapy plus anti-angiogenesis (CA) and chemotherapy alone (CM). Efficacy was evaluated according to the RECIST 1.1version, and calculated the objective response rate (ORR) and disease control rate (DCR). Survival curves were plotted using the Kaplan-Meier method, and the median progression-free survival (PFS) was calculated. Differences among survival curves of the six groups were assessed using the log-rank test. A total of 237 advanced NSCLC patients with EGFR mutations were included in this study. Of the 160 patients who received immunotherapy, 57 received ICI monotherapy, 27 received ICI plus anti-angiogenesis therapy, 43 received ICI plus chemotherapy, and 33 received ICI plus anti-angiogenesis plus chemotherapy. 77 patients received standard chemotherapy, of which 30 received chemotherapy plus anti-angiogenesis and 47 received chemotherapy alone. Patients in ICA group showed significant longer PFS than IM (7.2 vs 1.9 months, P=0.011), IA (7.2 vs 4.8 months, P=0.009) and CM group (7.2 vs 4.4 months, P=0.005). There was no significant difference in PFS between the ICA and IC (7.2 vs 5.6 months, P=0.104) or CA (7.2 vs 6.7 months, P=0.959) group. Meanwhile, the ICA group showed the highest ORR and DCR (36.4% and 90.9%) compared to the other five groups. The IC group had a higher ORR than the IA and CA group (32.6% vs 7.4% vs 10.0%, respectively), but the DCR was comparable (79.1% vs 74.1% vs 76.7%, respectively). The ORR of the CM group was 6.4% and the DCR was 66.0%. IM group showed the lowest ORR and DCR (1.8% and 36.8%). Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 9 (27.3%) patients in the ICA group, 6 (20.0%) in the CA group, 7 (14.9%) in the CM group, 5 (11.6%) in the IC group, 5 (8.8%) in the IM group, and 2 (7.4%) in the IA group. NSCLC patients with positive EGFR mutations after EGFR-TKIs failure received subsequent immunotherapy plus anti-angiogenesis and chemotherapy are likely to have more benefits in ORR, DCR and mPFS.


Tumours composed of fat are no longer a simple diagnosis: an overview of fatty tumours with a spindle cell component.
This is a review of the morphological spectrum of fatty tumours containing a component of spindle cells, highlighting the immunohistochemical and cytogenetic workup that is now mandatory for accurate diagnosis, with the goal of providing a practical approach for practising surgical pathologists. There have been significant advances in recent years in classifying and understanding the pathogenesis of fatty tumours with spindle cells, based on the correlation of histological, immunohistochemical and cytogenetic/molecular findings. In spite of this, morphological diagnosis and accurate classification of fatty tumours with spindle cells can be challenging to diagnostic pathologists. A group of three lesions: spindle cell lipoma, mammary-type myofibroblastoma and cellular angiofibroma share morphological features and are united by retinoblastoma protein (pRb) loss. Closely allied to these lesions, especially spindle cell lipoma is the newly designated atypical spindle cell lipomatous tumour, which shares morphological, immunohistochemical and cytogenetic features with the trio of tumours lacking nuclear pRb. All of these lesions lack MDM2 and CDK4 amplification as well and separation is based on clinical features, principally location. Atypical lipomatous tumour or well-differentiated liposarcoma shows retention of pRb but overexpression and amplification of MDM2. Fatty tumours with spindle cells need to be extensively sampled, with careful attention paid to cellular atypia and location, and they need to have immunohistochemical workup with pRb, MDM2, desmin, CD34 and p16. In addition, cytogenetic analysis for MDM2 and CDK4 amplification has become crucial for the proper identification of these lesions.


Evaluation of the validated intraoperative bleeding scale in liver surgery: study protocol for a multicenter prospective study.
Surgical hemostasis has become one of the key principles in the advancement of surgery. Hemostatic agents are commonly administered in many surgical specialties, although the lack of consensus on the definition of intraoperative bleeding or of a standardized system for its classification means that often the most suitable agent is not selected. The recommendations of international organizations highlight the need for a bleeding severity scale, validated in clinical studies, that would allow the selection of the best hemostatic agent in each case. The primary objective of this study is to evaluate the VIBe scale (Validated Intraoperative Bleeding Scale) in humans. Secondary objectives are to evaluate the scale's usefulness in liver surgery; to determine the relationship between the extent of bleeding and the hemostatic agent used; and to assess the relationship between the grade of bleeding and postoperative complications. Prospective multicenter observational study including 259 liver resections that meet the inclusion criteria: patients scheduled for liver surgery at one of 10 medium-high volume Spanish HPB centers using an open or minimally invasive approach (robotic/laparoscopic/hybrid), regardless of diagnosis, ASA score <4, age ≥18, and who provide signed informed consent during the study period (September 2023 until the required sample size has been recruited). The participating researchers will be responsible for collecting the data and for reporting them to the study coordinators. This study will allow us to evaluate the VIBe scale for intraoperative bleeding in humans, with a view to its subsequent incorporation in daily clinical practice. https://clinicaltrials.gov/ct2/show/NCT05369988?term = serradilla&draw = 2&rank = 3, [NCT0536998].


Passive muscle length changes affect twitch potentiation in power athletes.
A conditioning maximal voluntary muscle action (MVC) has been shown to induce postactivation potentiation, that is, improved contractile muscle properties, when muscles are contracted isometrically. It is still uncertain how the contractile properties are affected during ongoing muscle length changes. The purpose of this study was to investigate the effects of a 6-s conditioning MVC on twitch properties of the plantarflexors during ongoing muscle length changes. Peak twitch, rate of torque development, and rate of torque relaxation, rising time, and half relaxation time were measured from supramaximal twitches evoked in the plantarflexors of 11 highly trained athletes. Twitches were evoked before a 6-s MVC and subsequently on eight different occasions during a 10-min recovery for five different modes: fast lengthening, slow lengthening, isometric, fast shortening, and slow shortening of the plantarflexors. The magnitude and the duration of effects from the conditioning MVC were significantly different between modes. Peak twitch, rate of torque development, and rate of torque relaxation significantly increased for all modes but more so for twitches evoked during fast and slow shortening as compared with lengthening. Rising time was reduced in the lengthening modes but slightly prolonged in the shortening modes. Half relaxation time was significantly reduced for all modes, except fast lengthening. The findings show that the effects of a conditioning MVC on twitch contractile properties are dependent on direction and velocity of ongoing muscle length changes. This may imply that functional enhancements from a conditioning MVC might be expected to be greatest for concentric muscle actions but are still present in isometric and eccentric parts of a movement.


Staged intact canal wall tympanoplasty for treatment of middle ear cholesteatoma.
Results of surgery for middle ear cholesteatoma were investigated in 202 ears of 197 patients who had undergone surgery by the staged intact canal wall technique. Surgical procedures used in the second stage for prevention of a retraction pocket were classified into three types: Type S1, no scutumplasty; Type S2, scutumplasty; Type S3, scutumplasty plus mastoid obliteration. Recurrent cholesteatoma was found in 9 ears (4%) and retraction pocket in 47 ears (23%). They occurred between 2 and 120 months (average: 26 months) after the second stage, most frequently at 1 to 3 years. The incidence was higher after Type S3 surgery than after the other types, probably because the middle ear was severely involved in patients who were indicated Type S3 surgery. For prevention of a retraction pocket, bone putty and cartilage were proved to be appropriate materials for scutumplasty, and hydroxyapatite for mastoid obliteration. As the retraction pocket tended to recur in patients with the pocket at the second stage, these patients needed obliteration of the mastoid cavity to prevent a retraction pocket. Postoperative hearing was evaluated according to the criteria proposed by the Japan Society of Clinical Otology. Of 145 ears of the 142 patients who were followed for more than 1 year, 118 ears (81%) the surgery was judged successful. The success rate in hearing was in good accordance with the condition of the tympanic membrane.


Comparison of tuberculous and pyogenic epididymal abscesses: clinical, gray-scale sonographic, and color Doppler sonographic features.
The purpose of this study was to evaluate the capability of clinical, gray-scale sonographic, and color Doppler sonographic features for differentiating tuberculous and pyogenic epididymal abscesses. Retrospective analysis was performed in 10 cases of tuberculous epididymal abscess and in 13 cases of pyogenic epididymal abscess. The following clinical, gray-scale sonographic, and color Doppler sonographic features were analyzed: patient's age; duration of symptoms; scrotal tenderness; presence of sinus tract; concurrent tuberculosis in other organs; location, size, and echogenicity of the abscess; hyperechoic rim; testicular involvement; hydrocele; and blood flow in the epididymal lesion. Tuberculous epididymal abscess had a longer duration of symptoms (p = 0.0001) and a lower frequency of scrotal tenderness (p = 0.0048) than pyogenic epididymal abscess. The size of the abscess was larger in tuberculous epididymal abscess than in pyogenic epididymal abscess (p = 0.0002). The degree of blood flow in the peripheral portion of the abscess was lower in tuberculous epididymal abscess (p = 0.001). The patient's age, location and echogeninicity of the abscess, presence of sinus tract, hyperechoic rim, testicular involvement, and hydrocele did not differ between the tuberculous and pyogenic epididymal abscesses. Some clinical findings, gray-scale sonography, and color Doppler sonography were useful in differentiating tuberculous epididymal abscess from pyogenic epididymal abscess. The presence of long-term scrotal swelling without tenderness and a lower degree of blood flow in the peripheral portion of a large abscess are suggestive of tuberculous epididymal abscess.


Gene abnormalities in patients with hemophagocytic lymphohistiocytosis.
Hemophagocytic lymphohistiocytosis is thought to occur as a primary (familial) form or secondary to infection or malignancy. Recently, several defects in genes important for immune functions were identified in patients with HLH. These include mutations in perforin, the gamma common chain of the receptor for interleukin-2, Slap and purine nucleoside phosphorylase. Since abnormal function of these genes is associated with a wide clinical spectrum, HLH is probably another manifestation of immune deficiency and a thorough immune evaluation should be done in all such patients.


A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system.
While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer. Since the mechanistic investigation of pharmacological modulators in a drug discovery setting is largely compound- and mechanism-centric but not comprehensive in terms of immune system impact, we developed a human tissue based functional assay platform to evaluate the impact of pharmacological modulators on a range of innate and adaptive immune functions. Here, we demonstrate that it is possible to generate a qualitative and quantitative immune system impact of pharmacological modulators, which might help better understand and predict the benefit-risk profiles of these compounds in the treatment of immune disorders.


A cohort study of low Apgar scores and cognitive outcomes.
To investigate the association of brief (0-5 minutes) and prolonged (>5 minutes) low Apgar scores (<7) in non-encephalopathic infants with educational achievement at age 15-16 and intelligence quotients (IQs) at age 18. Population-based record-linkage cohort study of 176 524 male infants born throughout Sweden between 1973 and 1976. Data from the Medical Birth Register were linked to Population and Housing Censuses, conscription medical records (IQ), and school registers (summary school grade). Infants were classified according to the time for their Apgar score to reach 7 or above. Premature infants and those with encephalopathy were excluded. Infants with brief (OR = 1.14 (1.03-1.27)) or prolonged (OR = 1.35 (1.07-1.69)) low Apgar scores were more likely to have a low IQ score. There was an increased risk of a low IQ score (p = 0.003) the longer it took the infant to achieve a normal Apgar score. There was no association between brief (OR = 0.96 (0.87-1.06)) or prolonged (OR = 1.01 (0.81-1.26)) low Apgar scores and a low summary school grade at age 15-16, or evidence for a trend in the risk of a low school grade (p = 0.61). The estimated proportion with an IQ score below 81 due to transiently low Apgar scores was only 0.7%. Infants in poor condition at birth have increased risk of poor functioning in cognitive tests in later life. This supports the idea of a "continuum of reproductive casualty", although the small individual effect suggests that these mild degrees of fetal compromise are not of clinical importance.