Correlation between response to cisplatinum-combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck.
Induction chemotherapy, followed by surgery and/or radiotherapy was utilized in patients with advanced squamous cell carcinoma of the head and neck. During these trials, the authors observed that response to chemotherapy predicts further response to subsequent radiotherapy. This study was comprised of 57 patients with 60 separate neoplasms who demonstrated less than complete response (partial or no response) to initial treatment with a combination chemotherapy containing cisplatin. Subsequently radiotherapy, either 5000 rad preoperatively or 6600 rad as definitive therapy, was employed. Forty-one of the 42 tumors with initial partial response to chemotherapy also responded to radiotherapy (97.6%). Only one of the 18 tumors that initially failed to respond to chemotherapy subsequently responded to radiotherapy (5.5%). This observation suggests that patients with head and neck cancer sensitive to initial chemotherapy share parameters that are also radiation sensitive.


Role of cell shape in growth control.
Tissue culture plastic adhesivity was precisely varied by applying different concentrations of poly(2-hydroxyethyl methacrylate). The extent of cell spreading was thus accurately controlled so that cells cultured on these substrata could be held at any one of a graded series of quantitated cell shapes. Cell shape was found to be tightly coupled to DNA synthesis and growth in nontransformed cells. These findings suggest a mechanism that is important in growth control of mammalian cells, and provide a more fundamental interpretation of such phenomena as density dependent inhibition of cell growth and anchorage dependence.


Factor-specific changes in oxidative burst response of human neutrophils in skin-window exudates.
Human neutrophils were isolated from blood and aseptic inflammatory exudates. The respiratory burst response was measured as superoxide (O2-) production by a microplate assay system and polarographically as oxygen consumption. Exudate cells exhibited a respiratory burst in response to n-formyl-methionyl-leucyl-phenyl-alanine (FMLP) that was two- to threefold higher than the burst exhibited by peripheral blood cells. The O2- production induced by substance P was also found to be fivefold higher in exudate cells, while the metabolic response to other stimulants such as concanavalin A (con A), phorbol-myristate acetate (PMA), NaF, and immunocomplexes was not primed. Serum-treated zymosan (STZ)-stimulated activity was primed by only 11%. In contrast, superoxide production in response to tumor necrosis factor-alpha (TNF) was decreased in exudate versus blood cells by about 50%. Therefore, the skin-window cells, compared to blood cells, appear to be at the same time primed, unmodified, and desensitized, according to the different stimulants employed.


Iron(III) catalysed synthesis of unsymmetrical di and trisubstituted ureas--a variation of classical Ritter reaction.
An application of the classical Ritter reaction for the synthesis of unsymmetrical di and trisubstituted ureas catalyzed by FeCl(3) is described. The protocol is of significant interest in view of the easy availability of precursors, mild reaction conditions employed and interestingly its applicability for the alkylation of alcohols capable of forming stable carbocationic intermediates even to the sterically hindered moieties.


Recurrent cervical cancer with PD-L1 amplification treated with nivolumab: A case enrolled in the BELIEVE trial.
Patients with cervical cancer benefiting from immune checkpoint inhibitors (ICIs) are limited. Recently, PD-L1 amplification has been attracted attention as a reliable marker of ICIs. A 47-year-old woman with stage IIB cervical cancer experienced disease progression during postoperative adjuvant chemotherapy. Cancer genomic profiling revealed that the tumor was microsatellite stable with PD-L1 amplification, therefore, nivolumab was administered by enrolling in the BELIEVE trial. Despite nivolumab treatment, remarkable disease progression was observed. At the beginning of nivolumab treatment, the patient already had multiple liver metastases with severe systemic inflammation as indicated by a high neutrophil-to-lymphocyte ratio (NLR), both of which are negative predictive markers for ICI. Despite the presence of PD-L1 amplification, nivolumab was ineffective in cancer progression, which may be attributable to the presence of liver metastasis and high NLR. ICI is recommended to be administered at an early stage of cancer treatment to enhance its effectiveness.


Serum metabolomic adaptations following a 12-week high-intensity interval training combined to citrulline supplementation in obese older adults.
Physical activity and nutrition play important roles in preventing adverse health outcomes that accompany aging. It has been shown that high-intensity interval training (HIIT) combined with citrulline (CIT) supplementation can improve physical and functional capacities. The aim of this study was to evaluate serum metabolites following a 12-week HIIT combined or not with CIT in obese older adults, and to correlate the metabolic changes with clinico-biological parameters changes. Eighty-six obese older adults completed a 12-week HIIT program combined with a 10 g daily supplementation of either CIT or placebo (PLA) during a double-blinded randomized interventional trial. Only participants with blood samples at T0 (before the intervention) and/or T12 (after the intervention) were included in our sub-analysis (HIIT-PLA-T0: n = 44 and HIIT-PLA-T12: n = 28; HIIT-CIT-T0: n = 39 and HIIT-CIT-T12: n = 42). Serum samples were analyzed by different liquid or gas phase chromatography methods coupled to mass spectrometry. Among the identified metabolites, 44 changed significantly following the 12-week intervention (Time effect), and 10 of them were more affected when HIIT was combined with CIT (Time × Supp effect). Arginine increased significantly due to the 12-week intervention. Correlation analyses demonstrated that decreased triglyceride (TG) (16:1/18:1/16:0) and aspartic acid significantly correlated with a reduction of adiposity-related parameters (fat mass, leg lean mass, leptin, total triglycerides and low-density lipoprotein). Arginine, TG (16:1/18:1/16:0) and aspartic acid might constitute biomarkers of cardiometabolic health and adiposity. Further studies are needed to confirm these associations and understand the underlying mechanisms.Highlights A 12-week intervention involving high-intensity interval training (HIIT) with or without citrulline (CIT) supplementation induced adaptations in the serum metabolome of obese older adults through significant changes in 44 metabolites.Changes in 23 metabolites were observed when a CIT supplementation was administered along with a 12-week HIIT intervention.TG (16:1/18:1/16:0) correlated with several adiposity parameters including leptin, triglycerides, legs lean mass.Aspartic acid correlated with several adiposity parameters including leptin, LDL cholesterol as well as android, arms and trunk fat mass.


Role of adenosine after antral pulmonary vein isolation of paroxysmal atrial fibrillation: A randomized controlled trial.
Adenosine can reveal dormant pulmonary vein (PV) conduction after PV isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). However, the impact of elimination of adenosine-provoked dormant PV conduction after PVI has not been formally evaluated. The purpose of this study was to determine whether ablation of PV reconnections unmasked by adenosine improves outcomes. Patients with paroxysmal AF (n = 129) were randomized to receive either adenosine (n = 61) or no adenosine (n = 68) after PVI. Dormant conduction revealed by adenosine after PVI was ablated until all adenosine-mediated reconnections were eliminated. Thereafter, both groups received isoproterenol. Acute reconnection was seen in 23 patients (37%) in the adenosine group. There was a significant difference between the number of PVs reconnected if patients were given adenosine >60 minutes after initial PVI compared to those who received adenosine <60 minutes after initial PVI (3/32 [9.4%] vs 24/32 [75%], P <.0001). Patients who did not receive adenosine had more PV reconnections after isoproterenol infusion compared to patients in the adenosine group (17/68 [25.0%] vs 5/61 [8.2%], P = .018). There was no difference in the rate of AF recurrence in patients who received adenosine (24/61 [39%]) compared to control patients (23/68 [34%], log-rank P = .83). Adenosine can reveal dormant conduction in more than one-third of patients with paroxysmal AF undergoing PVI. However, adenosine administration, and additional ablation of the resultant connections, does not improve long-term outcomes compared to a protocol that includes isoproterenol infusion.


Changes in trypsin and chymotrypsin inhibitory activity on soaking of redgram (Cajanus cajan L.).
Changes in trypsin and chymotrypsin inhibitory activity of redgram seeds on soaking in distilled water, different salt solutions and mixed salt solution were investigated. Reduction in trypsin and chymotrypsin inhibitory activity was observed on soaking in salt solutions in comparison to soaking in distilled water. Maximum loss of trypsin and chymotrypsin inhibitory activity was observed on soaking the seeds in mixed salt solution.


Perfusion of the septum of the rabbit with vasopressin antiserum enhances endotoxin fever.
The septal region of the brains of conscious, adult, male New Zealand White rabbits were perfused by means of a push-pull system before and after an intravenous administration of bacterial pyrogen extracted from Salmonella abortus equi. Perfusion of the septal area with sucrose solution (260 mM) had no significant effect on the resulting fever (1.13 +/- 0.09 degrees C) when compared to a control fever without the push-pull perfusion (1.06 +/- 0.12 degrees C). Arginine vasopressin (AVP) added to the perfusing solution (20 micrograms/ml) caused a significant attenuation of the fever (0.81 +/- 0.20 degrees C). An antiserum specific to AVP when added to the perfusing solution resulted in a fever which was significantly greater (2.38 +/- 0.13 degrees C) than the control. Radioimmunoassay of perfusates collected from the control perfusions before and during fever showed that, as the body temperature rose in response to the pyrogen, the level of AVP in the perfusate collected from the septal area decreased. These results provide further evidence that AVP may act in the septal area of the brain to modulate the febrile response.


Thermoplastic starch/polyvinyl alcohol blends modification by citric acid-glycerol polyesters.
Thermoplastic starch/polyvinyl alcohol (TPS/PVA) films have limitations for being used in long-term applications due to starch retrogradation. This leads to plasticizer migration, especially when low molecular weight plasticizers such as glycerol, are used. In this work, we employed mixtures of oligomers based on glycerol citrates with higher molecular weight than glycerol as plasticizers for potato-based TPS/PVA blends obtained by melt-mixing. This constitutes an alternative to reduce plasticizer migration while keeping high swelling degree, and to provide high mechanical performance. The novelty lies in the usage of these oligomers by melt-mixing technique, aspect not deeply explored previously and that represents the first step towards industrial scalability. Prior to the blending process, oligomers mixtures were prepared with different molar ratios of citric acid (0-40 mol%) and added them. This minimizes the undesirable hydrolysis effect of free carboxylic groups on starch chains. The results demonstrated that the migration of plasticizers in TPS/PVA blends decreased by up to 70 % when the citric acid content increased. This reduction was attributed to the higher molecular weight (the majority in the range 764-2060 Da) and the 3D structure of the oligomers compared to using raw glycerol. Furthermore, the films exhibited a 150 % increase in Young's modulus and tensile strength without a reduction in elongation at break, while maintaining a high gel content, due to a moderate crosslinking.


Reactive oxygen species activate and tetracyclines inhibit rat osteoblast collagenase.
Recent studies have demonstrated that tetracyclines (TCs) scavenge reactive oxygen species (ROS). Hypochlorous acid (HOCl), an ROS produced by neutrophils, has been shown to activate neutrophil procollagenase. The objective of the present study was to determine whether (1) HOCl also activated osteoblast procollagenase and (2) TCs inhibited this enzyme in the presence of HOCl. HOCl (5 microM) activated the proenzyme approximately sixfold (P < 0.01) from the medium of PTH-treated UMR-106-01 osteoblastic osteosarcoma cells as determined by functional collagenase assay (3H-methyl-labeled collagen substrate). Doxycycline (50-400 microM) and chemically modified tetracycline, CMT-1 (100-400 microM), significantly inhibited collagenase activity 50-90% and 40-80%, respectively, in the presence of 5 microM HOCl. Concentrations of 6-25 microM doxycycline and 10-50 microM CMT-1 had no significant effect. Furthermore, an excess concentration of cation (50 mM CaCl2 or 50 microM ZnCl2) added to the incubation mixtures containing either doxycycline or CMT-1 did not restore collagenase activity, as demonstrated by SDS-PAGE-fluorography. These data suggested that TCs reduced available HOCl and thus prevented the hypochlorous acid conversion of the osteoblast proenzyme to active collagenase. TCs may have therapeutic potential in the treatment of periodontitis and other diseases by several mechanisms that inhibit pathologic collagen breakdown.


HER2 copy number quantification in primary tumor and cell-free DNA provides additional prognostic information in HER2 positive early breast cancer.
The quantitative relationship between HER2 copy number and prognosis in HER2 positive adjuvant setting remain controversial, and few studies have focused on adjuvant setting to illustrate the potential clinical relevance of HER2 in cfDNA. Our study aim to develop a novel method in HER2 quantification and explore the relationship between HER2 copy number in primary tumors or cfDNA and prognosis in HER2 positive early breast cancer. Two hundred and two patients with early breast cancer were prospectively included in a study where primary tumors, matching non-cancer breast tissue, corresponding plasma, and the plasma from 20 healthy volunteers were collected. Cox proportional hazard analysis was employed to determine the prognostic value of HER2 gene copy number in tissue and cfDNA. Tissue based nomograms and time-dependent decision curve analysis were used to evaluate the practicality of HER2 copy number stratification. HER2 amplification by CNVplex demonstrated a robust concordance with FISH (concordance 89.2%). A three-tiered system of tissue and a two-tiered system of cfDNA classification were shown to be independent prognostic factors. A tissue copy number-based nomogram was fitted and further evaluation revealed a good performance in discrimination (c statistic 0.801) and calibration. We first report CNVplex as a viable alternative for HER2 detection. Quantitative evaluation of HER2 presents tremendous potential for use in risk stratification. We also uncover the potential for using HER2 copy number in cfDNA as a biomarker for prognosis in a HER2 positive adjuvant setting.


Agriculture and climate change: Potential for mitigation in Spain.
Agriculture and forestry activities are one of the many sources of greenhouse gas (GHG) emissions, but they are also sources of low-cost opportunities to mitigate these emissions compared to other economic sectors. This paper provides a first estimate of the potential for mitigation in the whole Spanish agriculture. A set of mitigation measures are selected for their cost-effectiveness and abatement potential and an efficient mix of these measures is identified with reference to a social cost of carbon of 40 €/tCO2e. This mix of measures includes adjusting crop fertilization and managing forests for carbon sequestration. Results indicate that by using the efficient mix of mitigation measures the annual abatement potential could reach 10 million tCO2e, which represents 28% of current agricultural emissions in Spain. This potential could further increase if the social cost of carbon rises covering the costs of applying manure to crops. Results indicate also that economic instruments such as input and emission taxes could be only ancillary measures to address mitigation in agriculture. These findings can be used to support the mitigation efforts in Spain and guide policymakers in the design of country-level mitigation strategies.


Effects of press-in airflow rate and the distance between the pressure duct and the side wall on ventilation dust suppression performance in an excavating tunnel.
The efficiency of mine excavation has been significantly enhanced by continuing improvements in tunneling capabilities; however, this has also resulted in serious environmental pollution and greater safety risks for workers. To ensure safe production, the focus of this study is on the effect of varying the air pressure and the distance between the air pressure cylinder and the side wall settings on dust dispersion behavior and dust control in excavated tunnels. We also investigated temporal-spatial dust diffusion rules in tunnels by combining numerical simulation data with field measurement results. Through further analysis, when the pressure air volume and the exhaust air volume are both equal to 250 m3/min, the dust diffusion distance could be fitted as: [Formula: see text]. When the exhaust air volume is equal to 250 m3/min, dust control effects were improved as the pressure air volume decreased, becoming optimal when the pressure air volume dropped to 150 m3/min. Under these conditions, areas of high dust pollution were contained within 16 m of the cutting face, and the dust diffusion distance satisfied the formula: [Formula: see text]. When the pressure air volume is fixed, the change of the distance between the pressure air cylinder and the side wall has little effect on the dust diffusion. When the distance is 1.5 m, the dust control effect is the best, and the high dust pollution area is controlled within 14 m of the cutting surface. This alleviated dust pollution to a certain degree, thereby enhancing the air quality and ensuring safer production. This study provides a new understanding of the environmentally sustainable development of tunnels and is of great significance for clean production.


Quantitative Imaging Parameters of Contrast-Enhanced Micro-Computed Tomography Correlate with Angiogenesis and Necrosis in a Subcutaneous C6 Glioma Model.
The aim of this work was to systematically obtain quantitative imaging parameters with static and dynamic contrast-enhanced (CE) X-ray imaging techniques and to evaluate their correlation with histological biomarkers of angiogenesis in a subcutaneous C6 glioma model. Enhancement (E), iodine concentration (CI), and relative blood volume (rBV) were quantified from single- and dual-energy (SE and DE, respectively) micro-computed tomography (micro-CT) images, while rBV and volume transfer constant (Ktrans) were quantified from dynamic contrast-enhanced (DCE) planar images. CI and rBV allowed a better discernment of tumor regions from muscle than E in SE and DE images, while no significant differences were found for rBV and Ktrans in DCE images. An agreement was found in rBV for muscle quantified with the different imaging protocols, and in CI and E quantified with SE and DE protocols. Significant strong correlations (Pearson r > 0.7, p < 0.05) were found between a set of imaging parameters in SE images and histological biomarkers: E and CI in tumor periphery were associated with microvessel density (MVD) and necrosis, E and CI in the complete tumor with MVD, and rBV in the tumor periphery with MVD. In conclusion, quantitative imaging parameters obtained in SE micro-CT images could be used to characterize angiogenesis and necrosis in the subcutaneous C6 glioma model.


Insecticide resistance monitoring in field populations of Chilo suppressalis Walker (Lepidoptera: Crambidae) from central China.
Chilo suppressalis Walker (Lepidoptera: Crambidae) is a devastating rice crop pest in China. Chemical insecticides have been used to effectively managing C. suppressalis field populations in most of China's agricultural regions. However, due to the intensive and extensive application of these insecticides, C. suppressalis has developed widespread resistance to many active ingredients. Thus, insecticide resistance development is a genuine concern for all crop specialists and growers. In this study, using the topical application method, we assessed the susceptibility of forty-six field populations of C. suppressalis to three insecticides in three Central Chinese provinces from 2010 to 2021. Our findings revealed that field populations of C. suppressalis built moderate to high levels of resistance to triazophos (Resistance Ratio (RR) = 41.9-250.0 folds), low to moderate levels of resistance to chlorpyrifos (RR = 9.5-95.2 folds), with the exception of the Zhijiang population in 2013 and the Xinyang population in 2015 at 4.8 folds and 3.4 folds resistance rates, respectively, despite showing susceptibility, and low and moderate levels of resistance to abamectin (RR = 4.1-53.5 folds). There were significant correlations between the activity of the detoxification enzymes (CarE) and the log LD50 values of triazophos. These results should help effective insecticide resistance management strategies reduce the risk of rapid build-ups of resistance to insecticides and slow down the process of selection for insecticide resistance.


Control of Herbaspirillum seropedicae NifA activity by ammonium ions and oxygen.
The activity of a truncated form of Herbaspirillum seropedicae NifA in different genetic backgrounds showed that its regulatory domain is involved in nitrogen control but not in O2 sensitivity or Fe dependence. The model for nitrogen control involving PII could thus apply to the proteobacteria at large. NifA may have a role in controlling ADP-ribosylation of nitrogenase in Azospirillum brasilense.


The Stress Check Program: a new national policy for monitoring and screening psychosocial stress in the workplace in Japan.
The Japanese government launched a new occupational health policy called the Stress Check Program. This program mandates that all workplaces with 50 or more employees conduct the Stress Check Program for workers at least once a year. This article gives a brief overview and critical review of the program. We reviewed relevant laws, guidelines, and manuals, as well as the policy development process. The policy and the components of the program were compared using available scientific evidence and trends in the management of psychosocial factors at work according to the policies and guidelines of international bodies and European countries. The process of program policy development was based on a discussion among employer and employee representatives, occupational health professionals, and mental health experts. Scientific evidence shows that mandated components of the program (i.e., feedback of stress survey results and physician's interview) may be ineffective. However, additional components recommended to employers, such as stress management skill provision and work environment improvement, in conjunction with the program may be effective in improving psychosocial stress at work. The Stress Check Program is unique compared with the global trend for psychosocial risk management because it focuses on the assessment of stress among individual workers. The new program may be effective in improving worker mental health by facilitating the psychosocial risk management approach in Japan. Concerns regarding the program include mass leakage of collected information, and possible disadvantages for workers labeled as having high stress.


Mining FDA resources to compute population-specific frequencies of adverse drug reactions.
Adverse drug reactions (ADRs) represent one of the main health and economic problems in the world. With increasing data on ADRs, there is an increased need for software tools capable of organizing and storing the information on drug-ADR associations in a form that is easy to use and understand. Here we present a step by step computational procedure capable of extracting drug-ADR frequency data from the large collection of patient safety reports stored in the Federal Drug Administration database. Our procedure is the first of its type capable of generating population specific drug-ADR frequencies. The drug-ADR data generated by our method can be made specific to a single patient population group (such as gender or age) or a single therapy characteristic (such as drug dosage, duration of therapy) or any combination of such.


Hair cycle induction by hair plucking in Mini rats.
Jcl:WistarTGN(ARGHGEN)1Nts rat (Mini rat) is a transgenic rat in which the growth hormone (GH) expression is suppressed by the presence of an antisense transgene for the rat GH gene, and the hair cycle of male Mini rats enters a long-lasting telogen phase after 8 weeks old. In the present study, effects of hair plucking on the hair cycle in the dorsal skin of 11-week-old male Mini rats were examined up to 54 days after the hair plucking. As a result, hair plucking brought about an anagen phase, and hair cycle arrest in telogen phase occurred again. Male Mini rats, having follicles in anagen-inducible long-lasting telogen phase, will offer a powerful tool for investigating the molecular nature and organization of the so-called hair cycle clock.


Low-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment.
Agomelatine (AGM) is the first melatonergic antidepressant. It suffers from low oral bioavailability (<5%) due to extensive hepatic metabolism. The current work aimed to develop an alternative AGM-loaded invasomes to enhance transdermal drug bioavailability. AGM-loaded invasomes were developed using two drug: lipid ratios (1:10 or 1:7.5), four terpene types (limonene, cineole, fenchone or citral) and two terpene concentrations (0.75% or 1.5%, w/v). They were characterized for drug entrapment efficiency (EE%), particle size (PS), zeta potential (ZP) and drug released percentages after 0.5h (Q0.5h) and 8h (Q8h). The optimum invasomes (I1, I2 and I4) were evaluated for morphology, drug-crystallinity, and ex-vivo drug flux. The variables influencing sonophoresis of the best achieved invasomal gel system (I2) were optimized including, ultrasound frequency (low, LFU or high, HFU), mode (pulsed or continuous), application period (10 min or 15 min) and duty cycle (50% or 100%). AGM pharmacokinetics were evaluated in rabbits following transdermal application of I2-LFU-C4 system, relative to AGM oral dispersion. The superiority of I2 invasomes [comprising AGM and phosphatidylcholine (1:10) and limonene (1.5% w/v)] was statistically revealed with respect to EE% (78.6%), PS (313 nm), ZP (-64 mV), Q0.5h (30.1%), Q8h (92%), flux (10.79 µg/cm2/h) and enhancement ratio (4.83). The optimum sonophoresis conditions involved application of LFU in the continuous mode for 15 min at a 100% duty cycle (I2-LFU-C4 system). The latter system showed significantly higher Cmax, and relative bioavailability (≈ 7.25 folds) and a similar Tmax (0.5 h). I2-LFU-C4 is a promising transdermal system for AGM.


Stimulus manipulation versus delayed feedback for teaching missing minuend problems to difficult-to-teach students.
The present study evaluated two procedures, Stimulus Manipulation and Delay Feedback Only, for teaching difficult-to-teach students to solve missing minuend problems (i.e., missing number problems starting with a minus sign). The Stimulus Manipulation procedure was directed at establishing the target skill with a minimum of errors. The training consisted of three phases of several steps each. The first phase was designed to establish a nonnumerical response to a prompt, the shape of which was gradually transformed into the final discriminative stimulus. The second phase was designed to extend the control of this stimulus to the numerical operations and to eliminate all supplementary stimuli. The third phase gradually eliminated the originally trained nonnumerical responses. The Delayed Feedback Only procedure included no stimulus manipulation and consisted of the experimenter giving only delayed right.wrong feedback on the solutions. The data indicate that both procedures resulted in all (N = 4) subjects (a) learning to solve the target problems, (b) generalizing this skill to similar, more advanced problems, and (c) maintaining it over multiple intervals of several consecutive weeks. However, systematic differences in error rate and long-term retention across training methods were observed, favoring the Stimulus Manipulation procedure.


Additive enhancement of neutrophil collagenase activity by HOCl and cathepsin G.
Using preparations of latent collagenase derived from neutrophil specific granule extracts, the relative effects of cathepsin G and HOCl on activation of neutrophil collagenase were determined using a quantitative collagenase assay. Enhancement of collagenase activity by cathepsin G and physiologically relevant concentrations of HOCl were comparable, but HOCl mediated collagenase activation was reversible in the presence of HOCl scavenger. Collagenase activity in preparations treated with cathepsin G and HOCL simultaneously or sequentially was significantly greater than activity in preparations treated with HOCl or cathepsin G alone. The results indicated additive, yet independent enhancing effects of HOCl and cathepsin G on activity of neutrophil collagenase.


Biological activity of sea bass (Dicentrarchus labrax L.) recombinant interleukin-1beta.
Biological activities of a putative mature sea bass interleukin-1beta peptide, produced as a recombinant protein (rIL-1beta) in Escherichia coli, have been investigated. The rIL-1beta contains a 6-histidine tag at the N-terminus, and protein purification has been achieved through this tag by affinity chromatography. Biological activities have been investigated both at the cellular and gene expression levels. In in vitro assays sea bass rIL-1beta induced the proliferation of murine D10.G4.1 cells and increased yeast phagocytosis by sea bass head kidney leukocytes. The purified cytokine was also tested in a lymphocyte-activation factor assay, where it induced the proliferation of sea bass thymocytes. Finally, in an in vivo assay, rIL-1beta administered intraperitoneally increased expression levels of the IL-1beta gene and activated macrophages to produce a cyclooxygenase 2 homologue (COX-2) gene in the head kidney.


Successful management of perforated duodenal diverticulitis with intra-abdominal drainage and feeding jejunostomy: a case report and literature review.
We report the clinical experience of one patient with perforated duodenal diverticulitis who was successfully treated by intra-abdominal drainage and feeding jejunostomy. A 53-year-old male patient visited our hospital due to acute onset of abdominal pain and distension. Physical examination revealed tenderness over the epigastric area and right-lower quadrant of the abdomen without obvious rebound tenderness or muscle guarding. Duodenal diverticulitis with a retroperitoneal abscess was identified by abdominal computed tomography scan. Surgical intervention was performed after the failure of conservative treatment. The operative findings were compatible with perforated duodenal diverticulitis, and intra-abdominal drainage of retroperitoneal abscess with simultaneous feeding jejunostomy was undertaken. The patient was doing well at the 4-month postoperative follow-up visit. We suggest the use of a conservative operative method, as opposed to conventional diverticulectomy and duodenorrhaphy, as an alternative approach for the management of this disorder, especially when conservative treatment has failed.


Left hepatic lobe herniation through an incisional anterior abdominal wall hernia and right adrenal myelolipoma: a case report and review of the literature.
Herniation of the liver through an anterior abdominal wall hernia defect is rare. To the best of our knowledge, only three cases have been described in the literature. A 70-year-old Mexican woman presented with a one-week history of right upper quadrant abdominal pain, nausea, vomiting, and jaundice to our Department of General Surgery. Her medical history included an open cholecystectomy from 20 years earlier and excessive weight. She presented with jaundice, abdominal distension with a midline surgical scar, right upper quadrant tenderness, and a large midline abdominal wall defect with dullness upon percussion and protrusion of a large, tender, and firm mass. The results of laboratory tests were suggestive of cholestasis. Ultrasound revealed choledocholithiasis. A computed tomography scan showed a protrusion of the left hepatic lobe through the anterior abdominal wall defect and a well-defined, soft tissue density lesion in the right adrenal topography. An endoscopic common bile duct stone extraction was unsuccessful. During surgery, the right adrenal tumor was resected first. The hernia was approached through a median supraumbilical incision; the totality of the left lobe was protruding through the abdominal wall defect, and once the lobe was reduced to its normal position, a common bile duct surgical exploration with multiple stone extraction was performed. Finally, the abdominal wall was reconstructed. Histopathology revealed an adrenal myelolipoma. Six months after the operation, our patient remains in good health. The case of liver herniation through an incisional anterior abdominal wall hernia in this report represents, to the best of our knowledge, the fourth such case reported in the literature. The rarity of this medical entity makes it almost impossible to specifically describe predisposing risk factors for liver herniation. Obesity, the right adrenal myelolipoma mass effect, and the previous abdominal surgery are likely to have contributed to incisional hernia formation.


Preliminary study of biosensor optimization for the detection of protein C.
Methods to develop an immuno-optical biosensor for the detection and monitoring of Protein C (PC) concentrations are described. A tapered quartz fiber is enclosed in a glass tube (capacity approximately 300 microliters) and monoclonal antibody against PC (anti-PC) is immobilized on the surface of this fiber. PC within a sample, when injected into the chamber, will bind to the anti-PC in a specific reaction. The system is then probed with a fluorophore tagged secondary antibody against PC, also binding to PC in a specific reaction. Excitation light is applied through the fiber, and the amount of fluorescence is correlated with the PC concentration in the sample. This study offers encouraging results for the detection of PC deficiency in real-time.


A novel combined RNA-protein interaction analysis distinguishes HIV-1 Gag protein binding sites from structural change in the viral RNA leader.
RNA-protein interactions govern many viral and host cell processes. Conventional 'footprinting' to examine RNA-protein complex formation often cannot distinguish between sites of RNA-protein interaction and sites of RNA structural remodelling. We have developed a novel technique combining photo crosslinking with RNA 2' hydroxyl reactivity ('SHAPE') that achieves rapid and hitherto unachievable resolution of both RNA structural changes and the sites of protein interaction within an RNA-protein complex. 'XL-SHAPE' was validated using well-characterized viral RNA-protein interactions: HIV-1 Tat/TAR and bacteriophage MS2 RNA/Coat Binding Protein. It was then used to map HIV-1 Gag protein interactions on 2D and 3D models of the viral RNA leader. Distinct Gag binding sites were identified on exposed RNA surfaces corresponding to regions identified by mutagenesis as important for genome packaging. This widely applicable technique has revealed a first view of the stoichiometry and structure of the initial complex formed when HIV captures its genome.


[Objective tinnitus and serous otitis media as symptoms of aberrant carotid artery (author's transl)].
Following a review of the literature a case of a middle ear aberrant carotid artery is reported. To avoid dangerous haemorrhage with surgery auscultation of the external auditory canal is necessary in every case of serous otitis media with a pulsating tympanic membrane. The main symptom in this condition is objective tinnitus.


A Contemporary Risk Analysis of Iatrogenic Transmission of Creutzfeldt-Jakob Disease (CJD) via Corneal Transplantation in the United States.
Creutzfeldt-Jakob disease (CJD) is a rare, fatal, neurodegenerative prion disease potentially transmissible through corneal transplantation. While statistical analyses performed two decades ago estimated the overall prevalence of CJD in the corneal donor pool to be low, the recent significant increase in corneal transplants performed and deaths due to CJD in the U.S. warrants a contemporary risk analysis. A literature review was conducted to determine the overall number of globally reported cases of CJD transmission through corneal transplantation. U.S. mortality and cornea donation data were utilized to estimate the age-stratified prevalence of undiagnosed, latent CJD in the cornea donor pool in 2018. A historical statistical analysis was performed to estimate the number of corneas from donors with latent CJD entering the U.S. donor pool for each year between 1979 and 2018. From these statistical analyses, risk factors of iatrogenic transmission were identified and summarized. Ten reported cases of iatrogenic transmission of CJD through corneal transplants were identified globally. In 2018, an estimated 3.8 corneas from donors with undiagnosed latent CJD potentially entered the pool of 111,703 transplant-intended corneas harvested from individuals aged 31-80. Between 1979 and 2018, an estimated 47 corneas may have entered the U.S. transplant-intended pool from donors with latent CJD aged 35 to 84. The advanced age of donors and a history of multiple transplants in recipients were both prominent risk factors for iatrogenic transmission. The 10 reported global cases of iatrogenic transmission likely under-represent the number of individuals with a coinciding history of death by CJD and prior corneal transplantation, as supported by our statistical analysis and lack of geographical diversity of reported cases. As effective screening methods develop and globalization of cornea transplantation broadens, it is of utmost importance that cornea transplantation history among victims of CJD should be investigated and reported.


Association of Upper Respiratory Streptococcus pneumoniae Colonization With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Adults.
Streptococcus pneumoniae interacts with numerous viral respiratory pathogens in the upper airway. It is unclear whether similar interactions occur with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We collected saliva specimens from working-age adults undergoing SARS-CoV-2 molecular testing at outpatient clinics and via mobile community-outreach testing between July and November 2020 in Monterey County, California. After bacterial culture enrichment, we tested for pneumococci by means of quantitative polymerase chain reaction targeting the lytA and piaB genes, and we measured associations with SARS-CoV-2 infection using conditional logistic regression. Analyses included 1278 participants, with 564 enrolled in clinics and 714 enrolled through outreach-based testing. The prevalence of pneumococcal carriage was 9.2% (117 of 1278) among all participants (11.2% [63 of 564] in clinic-based testing and 7.6% [54 of 714] in outreach-based testing). The prevalence of SARS-CoV-2 infection was 27.4% (32 of 117) among pneumococcal carriers and 9.6% (112 of 1161) among noncarriers (adjusted odds ratio [aOR], 2.73 [95% confidence interval (CI): 1.58-4.69). Associations between SARS-CoV-2 infection and pneumococcal carriage were enhanced in the clinic-based sample (aOR, 4.01 [95% CI: 2.08-7.75]) and among symptomatic participants (3.38 [1.35-8.40]), compared with findings within the outreach-based sample and among asymptomatic participants. The adjusted odds of SARS-CoV-2 coinfection increased 1.24-fold (95% CI: 1.00-1.55-fold) for each 1-unit decrease in piaB quantitative polymerase chain reaction cycle threshold value among pneumococcal carriers. Finally, pneumococcal carriage modified the association of SARS-CoV-2 infection with recent exposure to a suspected coronavirus disease 2019 case (aOR, 7.64 [95% CI: 1.91-30.7] and 3.29 [1.94-5.59]) among pneumococcal carriers and noncarriers, respectively). Associations of pneumococcal carriage detection and density with SARS-CoV-2 suggest a synergistic relationship in the upper airway. Longitudinal studies are needed to determine interaction mechanisms between pneumococci and SARS-CoV-2.


RNase H domain mutations affect the interaction between Moloney murine leukemia virus reverse transcriptase and its primer-template.
The active sites for the polymerase and nuclease activities of Moloney murine leukemia virus (M-MuLV) reverse transcriptase (RT) reside in separate domains of a single polypeptide. We have studied the effects of RNase H domain mutations on DNA polymerase activity. These mutant RTs displayed decreased processivity of DNA synthesis. We also compared complexes formed between primer-templates and mutant and wild-type reverse transcriptase (RT). Although M-MuLV RT is monomeric in solution, two molecules of RT bound DNA cooperatively, suggesting that M-MuLV RT binds primer-template as a dimer. Some mutant RTs with decreased processivity failed to form the putative dimer.


Gender differences in the factor structure of the Alcohol Use Disorders Identification Test in multinational general population surveys.
Most gender-specific studies of the Alcohol Use Disorders Identification Test (AUDIT) have focused on gender differences in thresholds for hazardous drinking. This study examines gender differences in the factor structure of the AUDIT in general-population surveys. General-population surveys from 15 countries provided 27,478 current drinkers' responses to the AUDIT and related measures. We used single-group confirmatory factor analysis (CFA) to evaluate goodness-of-fit of three hypothesized models for responses to the AUDIT by men and women in each country. Bayesian Information Criteria (BIC) using a maximum likelihood robust (MLR) estimator was evaluated to identify the best fitted model. We then assessed factorial invariance within country surveys where fit indices were acceptable for both genders. Gender-specific internal consistency and concurrent validity were also evaluated in all 15 countries. CFA revealed that the fit indices of 2-factor or 3-factor models were consistently better than fit indices for a 1-factor model in 14 of 15 countries. Comparisons of BIC values indicated that the 2-factor solution was the best fitted model. Factorial invariance tests in data from 3 countries indicated that the factor loadings and thresholds of the AUDIT were invariant across gender. The internal reliability and concurrent validity of AUDIT and its subscales were acceptable in both genders. A two-factor model best describes AUDIT responses across general-population surveys in 12 of 15 countries, with acceptable internal reliability and concurrent validity, and supports a gender-invariant structure in at least three of those countries.


All Things Considered: Examining Mentoring Relationships Between White Mentors and Black Youth in Community-Based Youth Mentoring Programs.
Community-based youth mentoring programs are popular interventions that serve a large number of Black youths throughout the country. Interestingly, the majority of mentors who volunteer their time for mentoring organizations identify as non-Hispanic White. This study examines how White mentors address topics acknowledging ethnic/racial identity and issues centered around social justice and recognize their own privileges when mentoring Black youth in community-based youth mentoring programs. The aims of the current study were to examine: (a) whether and how White volunteer mentors address ethnic/racial identity, racial socialization, and oppression in the mentoring relationship and (b) how White mentors' awareness of their own positionality and privilege impacted how they addressed ethnic/racial identity, racial socialization, and oppression in the mentoring relationship with Black youth. Utilizing a constructivist grounded theory approach, in-depth semi-structured interviews were conducted with 26 current and former mentors from six different Big Brothers Big Sisters community-based mentoring programs across the United States. Findings reveal that some mentors felt uncomfortable discussing issues centered around race and others do not think it is relevant at all. Further, findings demonstrated that mentoring Black youth significantly impacts mentors' perceived awareness of social issues and acknowledgment of privileges they hold. Current findings highlight the need for youth mentoring programs to provide training and resources to help White mentors discuss implications of race and broader social justice issues with the Black youth they mentor.


First assessments by specialist cancer nurses in the community: an ethnography.
The aim of the study is to explore how specialist cancer nurses carry out first assessments of patients in the community, their use of the Symptoms and Concerns Checklist (SCC) and their views on first assessments. An ethnographic approach was taken. The data were collected by use of non-participant observation of specialist nurses carrying out a first assessment of patients with cancer, followed by semi-structured interviews with six specialist nurses. Data were analysed using iterative thematic analysis. All the specialist nurses recognised the value of facilitating the patients' narrative. Use of the SCC was seen to jar with the overall theme of building relationships during the first assessment visit. It was recognised by the specialist nurses that the SCC was beneficial in prompting the patients to discuss psycho-social concerns. This study gives insight into the conflict and ambiguity for specialist nurses when using the SCC during the first assessment visit. It confirms the SCC as beneficial in cueing some patients to identify specific concerns and for these concerns to be recognised by the specialist nurses.


Anti-black Attitudes Are a Threat to Health Equity in the United States.
To assess the extent to which persistent racism shapes perspectives on public health policies aimed at improving health equity in the United States. Specifically we evaluate the relationship between implicit and explicit anti-black attitudes and support for the ACA at the beginning of the Trump administration. We use bivariate statistics to examine views toward the ACA, anti-black attitudes, and demographic variables. Using logistic regression, we examine how anti-black attitudes and demographic variables relate to participants stating that the ACA has worsened the quality of health care services in the United States. Data for this study come from the American National Election Studies 2016 Time Series Study, which targets US citizens age 18 and older currently living in the United States (N = 3245). Implicit anti-black attitudes, particularly among whites, are strongly associated with negative feelings toward the ACA. A measure of explicit racial prejudice has the opposite relationship among whites. These results suggest that whites are most critical of the ACA when they hold positive attitudes toward blacks but hold negative stereotypes about blacks' work ethic and reject policies to eliminate racial inequalities. Anti-black racial attitudes are a critical barrier to enacting health policies that stand to improve health equity in the United States. Public health practitioners and policymakers should consider racism as an essential barrier to overcome in the push for greater health equity in the United States.


[Protective effect against Schistosoma japonicum of recombinant fusion protein SjGST-32 in mice].
To explore the optimal immune doses of recombinant antigen rSjGST-32, with QuilA as adjuvant. BALB/c mice were immunized with doses of 50, 100 and 200 micrograms rSjGST-32/mouse plus 50 micrograms QuilA adjuvant. QuilA and PBS were used as controls. Levels of specific antibodies were detected by ELISA. The mice were challenged 4 weeks after last vaccination. Worms and eggs collected from the livers of mice were counted 45 days after challenge. As compared with the control groups, the worm reduction rate in the 50, 100 and 200 micrograms experiment groups was 38.1%, 47.8% and 48.8%, respectively. The reduction rate of liver eggs per gram (LEPG) was 39.1%, 53.5% and 53.6%, respectively, and the reduction rate of the liver eggs per female (LEPF) was 22.5%, 22.8% and 21.8%, respectively. The specific antibody titers in sera reached 1:51,200, 1:102,400 and 1:102,400, respectively before challenge. The results show that for vaccinating BALB/c mice, the optimal antigen dose is 100 micrograms of recombinant rSjGST-32 plus QuilA adjuvant.


Depletion of intracellular zinc induces apoptosis of cultured hippocampal neurons through suppression of ERK signaling pathway and activation of caspase-3.
Although Zinc depletion induces apoptosis in different cells and tissues, exact mechanism of this action of zinc depletion is not completely understood. In our previous study, the results suggested that the significant down-regulation of MEK/ERK signaling pathway was observed in zinc deficiency neurons. Here, we investigate whether, in hippocampal neurons, this increased rate of apoptosis induced by zinc depletion is the result of hypophosphorylation of ERK pathway. In this study, we found that NGF, ERK agonist, prevented neurons against TPEN-induced apoptosis, whereas TPEN-induced apoptosis was potentiated by U0126, inhibitors of ERK. Moreover, TPEN-induced caspase-3 activity was further increased by the pretreatment with U0126, but it was further decreased by the pretreatment with NGF. However, pretreatment of the cells with U0126 or NGF had no effect on the changes of Bcl-2 and Bax protein expression induced by zinc depletion. Thus, the results indicate that TPEN induces apoptosis of hippocampal neurons through inhibition of ERK and, in turn, activation of caspase-3.


Extensor indicis transfer versus palmaris longus transplantation in reconstruction of extensor pollicis longus tendon: a protocol for a systematic review.
This review will provide an overview of published data comparing transposition of the extensor indicis pollicis (EIP) tendon and palmaris longus (PL) tendon grafting in thumb extension reconstruction following loss of the extensor pollicis longus (EPL) tendon function. We will consider all studies comparing EIP and PL utilized to reconstruct thumb extension after injury/rupture of the EPL tendon. Only studies published in the English and German literature will be included. A systematic literature research will be performed across relevant health databases including the Cochrane Library, MEDLINE, and Google Scholar using the following keywords: ((extensor pollicis longus) OR EPL) AND ((extensor indicis) OR EIP OR (tendon transposition)) AND ((palmaris longus) OR (free tendon graft) OR (tendon transplantation)). Central tendencies will be reported in terms of means and standard deviations where necessary. If not reported, the standard deviation will be calculated from the standard error of the mean. Risk ratios will be calculated where possible. All calculations will be performed with a 95% confidence interval. Statistical significance will be set at P < 0.05. Adjusted effect estimates will be analyzed in preference to the unadjusted estimates, using inverse-variance weighted average. Pooled estimates will only be presented after consideration of both clinical and methodological heterogeneity of included studies. The review will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. SYSTEMATIC REVIEW REGISTRATION: The protocol was registered on PROSPERO CRD42019135735: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=135735.


The effectiveness of exercise for the management of musculoskeletal disorders and injuries of the elbow, forearm, wrist, and hand: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) collaboration.
The purpose of this systematic review was to evaluate the effectiveness of exercise compared to other interventions, placebo/sham intervention, or no intervention in improving self-rated recovery, functional recovery, clinical, and/or administrative outcomes in individuals with musculoskeletal disorders and injuries of the elbow, forearm, wrist, and hand. We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials from 1990 to 2015. Paired reviewers independently screened studies for relevance and assessed the risk of bias using the Scottish Intercollegiate Guidelines Network criteria. We synthesized the evidence using the best evidence synthesis methodology. We identified 5 studies with a low risk of bias. Our review suggests that, for patients with persistent lateral epicondylitis, (1) adding concentric or eccentric strengthening exercises to home stretching exercises provides no additional benefits; (2) a home program of either eccentric or concentric strengthening exercises leads to similar outcomes; (3) home wrist extensor strengthening exercises lead to greater short-term improvements in pain reduction compared to "wait and see"; and (4) clinic-based, supervised exercise may be more beneficial than home exercises with minimal improvements in pain and function. For hand pain of variable duration, supervised progressive strength training added to advice to continue normal physical activity provides no additional benefits. The relative effectiveness of stretching vs strengthening for the wrist extensors remains unknown for the management of persistent lateral epicondylitis. The current evidence shows that the addition of supervised progressive strength training does not provide further benefits over advice to continue normal physical activity for hand pain of variable duration.


Inhibition of thrombosis by a novel platelet selective S-nitrosothiol compound without hemodynamic side effects.
Platelet and endothelial production of bioactive nitric oxide (NO) is known to be impaired in acute coronary syndromes, thus compounds that release NO are useful candidates to restore NO-vascular functions. We have studied whether donation of NO with a novel platelet-selective S-nitrosothiol compound (LA810) at a systemic level can inhibit thrombosis elicited by damaged vessel wall (eroded and disrupted vessel wall) at hemodynamic conditions typical of patent and stenotic coronary arteries. Thrombogenicity was measured in the porcine experimental model and assessed as platelet-thrombus formation in the ex vivo Badimon perfusion chamber. After baseline perfusions, female pigs (Large WhitexLandrace) were given intravenous infusion of LA810 or GSNO standard S-nitrosothiol during 2 h. Changes in blood pressure, heart rate and in vitro platelet aggregation were measured. LA810 significantly decreased thrombus formation at any degree of vascular damage and shear rate (p<0.001) without hypotensive side-effects or heart rate variations. In contrast, inhibition of thrombus formation by GSNO required high doses associated to hypotensive episodes. Platelet aggregation induced by collagen was inhibited after nitrosothiol infusion in whole blood (LA810) and platelet rich plasma (LA810 and GSNO). In addition, there was a drug-dependent rise in platelet guanosine 3',5'-cyclic monophosphate (cGMP) levels. This new anti-ischemic NO-donor (NOd) LA810 that inhibits platelet function without hypotensive side-effects seems a highly efficacious strategy to reduce acute thrombosis triggered by coronary artery disease.


Intermolecular and intramolecular readout mechanisms in protein-DNA recognition.
Protein-DNA recognition plays an essential role in the regulation of gene expression. Regulatory proteins are known to recognize specific DNA sequences directly through atomic contacts (intermolecular readout) and/or indirectly through the conformational properties of the DNA (intramolecular readout). However, little is known about the respective contributions made by these so-called direct and indirect readout mechanisms. We addressed this question by making use of information extracted from a structural database containing many protein-DNA complexes. We quantified the specificity of intermolecular (direct) readout by statistical analysis of base-amino acid interactions within protein-DNA complexes. The specificity of the intramolecular (indirect) readout due to DNA was quantified by statistical analysis of the sequence-dependent DNA conformation. Systematic comparison of these specificities in a large number of protein-DNA complexes revealed that both intermolecular and intramolecular readouts contribute to the specificity of protein-DNA recognition, and that their relative contributions vary depending upon the protein-DNA complexes. We demonstrated that combination of the intermolecular and intramolecular energies derived from the statistical analyses lead to enhanced specificity, and that the combined energy could explain experimental data on binding affinity changes caused by base mutations. These results provided new insight into the relationship between specificity and structure in the process of protein-DNA recognition, which would lead to prediction of specific protein-DNA binding sites.


Risk factors and the overall characterization of Yersinia enterocolitica as an initial model of pathogen surveillance in the pig production system in Serbia.
A survey was undertaken to determine the overall prevalence of Yersinia enterocolitica in pigs of slaughter age and to characterize the isolates in relation to bio-serotype, the presence of virulence genes, genetic diversity, and antimicrobial resistance. Moreover, possible risk factors associated with Y. enterocolitica infection during the pre-harvested and harvested phase of pig production were studied. The overall Y. enterocolitica prevalence in the pigs was 10.4% (95% confidence interval, CI = 8.5-12.3%). The most common Y. enterocolitica bio-serotype was 4/O:3, accounting for 81.6% of investigated isolates. The pathogenicity of 63 Y. enterocolitica 4/O:3 isolates, originating from all infected farms, was confirmed by the presence of both the ail and ystA virulence-associated genes and the absence of ystB gene (100%). Characterization with PFGE of 63 confirmed Y. enterocolitica 4/O:3 isolates identified five different genotypes with shared identical genetic profiles (100% similarity) within each genotype. Isolates originating from farrow-to-finish farms were only resistant to ampicillin, while resistance to nalidixic acid, tetracycline, and chloramphenicol at fattening farms was also observed. Risk factors related to Y. enterocolitica pig infection include fattening farms (odds ratio, OR = 2.3, 95% CI = 1.4-3.8, P < 0.001), a 3-6 h lairage period (OR = 1.6, 95% CI = 1.0-2.6, P = 0.035) and winter season (OR = 3.8, 95% CI = 2.0-7.4, P < 0.001). In addition to the overall characterization of Y. enterocolitica isolates, identification of the main risks associated with infection allows better application of preventive measures to reduce the occurrence and distribution of Y. enterocolitica infection.


Inhibition of calcium oxalate crystallization in urine.
Chromatographic separation of urine showed inhibition of calcium oxalate (CaOx)-crystallization among substances with both large and small molecular weights. Ultrafiltration showed that approximately 80 per cent of the inhibiting activity, as determined in 2 per cent urine, originated from substances with a molecular weight above 1,000. Dialysed urine was diluted to 7.5 mmol of creatinine per 1 and supersaturated with respect to CaOx. The rate of crystallization in these samples was slower in normal subjects than in stone formers (p less than 0.05). The inhibiting activity in diluted urine from the two groups did not differ and neither did the concentration of alcian blue precipitable polyanions. From measurements in diluted urine it was apparent that inhibition was demonstrable with a urine concentration as low as 0.3 per cent.


The surplus human embryo: its potential for growth, blastulation, hatching, and human chorionic gonadotropin production in culture.
Early embryos that were unsuitable for transfer to patients or for cryopreservation were cultured either in a human tubal fluid (HTF) or a minimum essential medium (MEM). A significantly higher proportion of embryos developed to blastocysts in MEM (26.8%) than in HTF (14.5%). Approximately similar proportions of embryos formed blastocysts in MEM in the presence or absence of serum. The rate of embryo growth to blastocysts was similar in all media. Blastocyst hatching occurred in MEM + or - serum, but it failed to occur in HTF with serum. Released human chorionic gonadotropin (hCG) from hatched and intrazonal blastocysts was detected by day 8 after fertilization. The mean amount of hCG produced by day 14 was 19,500 mIU from hatched and 1,550 mIU from intrazonal blastocysts. Serum stimulated the output of hCG.


Role of Procalcitonin and C-Reactive Protein As Biomarkers of Infection in Children With Liver Disease.
Early and accurate identification of infection in patients with liver disease is challenging. The present study evaluated the role of procalcitonin (PCT) and C-reactive protein (CRP) as biomarkers of bacterial infection in children with liver disease. Demographic and clinical data of consecutive children admitted with acute liver failure (ALF) or decompensated chronic liver disease (DCLD) were collected. PCT and CRP were measured within 24 hours of admission. Blood and urine culture, chest x-ray, and ascitic fluid analysis were done. One hundred sixty-four children (113 boys, age 76 [0.5-204] months, ALF 69, DCLD 95) were enrolled. Seventy-seven (47%) had infection. Most common site was ascitic fluid (n = 35), followed by urinary tract (n = 26), pneumonia (n = 22), and blood stream infection (n = 16). Twenty-one children had multiple-site infections, 18 had severe sepsis, and 36 had systemic inflammatory response syndrome. PCT and CRP correlated with infection severity, higher in severe sepsis (8.3 [3.5-38] ng/mL and 4.1 [0.3-13.8] mg/dL) than only infection (0.89 [0.1-8] ng/mL and 1.7 [0.32-24] mg/dL) and no infection (0.3 [0.1-6.75] ng/mL and 0.3 [0.1-4.16 mg/dL]). Systemic inflammatory response syndrome was more common in patients with infection (31/77 vs 5/87, P = 0.00). PCT (>0.5 ng/mL) and CRP (>0.6 mg/dL) performed better in DCLD (AUC of 0.90 and 0.83) compared with patients with ALF (AUC of 0.73 and 0.69). PCT and CRP are reliable markers of infection and correlate with infection severity in children with liver disease. Their diagnostic accuracy is better in DCLD than ALF cases.


Effect of ethanol in preovulatory periods on brain monoamine levels.
The effects of two doses of ethanol (2 and 4 g/kg, i.p.) on the concentration of catecholamines (noradrenaline and dopamine), serotonin and 5-hydroxyindoleacetic acid in various regions of the rat brain were studied. The ethanol administration of both doses induces a significant decrease in the levels of hypothalamic noradrenaline. Similarly, 5-hydroxyindoleacetic acid levels in the same region and hemispheres are increased. The high dose produces an elevation in the concentration of midbrain dopamine. It was concluded that the hypothalamus is the brain region most sensitive to the action of ethanol and the effect of this substance differs according to the brain area.


Assessment of deep convolutional neural network models for mandibular fracture detection in panoramic radiographs.
The aim of this study was to develop automated models for the identification and detection of mandibular fractures in panoramic radiographs using convolutional neural network (CNN) algorithms. A total of 1710 panoramic radiograph images from the years 2016 to 2020, including 855 images containing mandibular fractures, were obtained retrospectively from the regional trauma centre. CNN-based classification models, DenseNet-169 and ResNet-50, were fabricated to identify fractures in the radiographic images. The CNN-based object detection models Faster R-CNN and YOLOv5 were trained to automate the placement of the bounding boxes to detect fractures in the radiographic images. The performance of the models was evaluated on a hold-out test set and also by comparison with residents in oral and maxillofacial surgery and oral and maxillofacial surgeons (experts) on a 100-image subset. The binary classification performance of the models achieved promising results with an area under the receiver operating characteristics curve (AUC), sensitivity, and specificity of 100%. The detection performance of the models achieved an AUC of approximately 90%. When compared with the accuracy of clinician observers, the identification performance of the models outperformed even an expert-level classification. In conclusion, CNN-based models identified mandibular fractures above expert-level performance. It is expected that these models will be used as an aid to improve clinician performance, with aided resident performance approximating that of expert level.


Fat on sale: role of adipose-derived stem cells as anti-fibrosis agent in regenerative medicine.
The potential use of stem cells for cell-based tissue repair and regeneration offers alternative therapeutic strategies for various diseases. Adipose-derived stem cells (ADSCs) have emerged as a promising source of stem cells suitable for transplantation in regenerative medicine and wound repair. A recent publication in Stem Cell Research & Therapy by Zhang and colleagues reports a new finding about the anti-fibrosis role of ADSCs and conditioned media derived from them on hypertrophic scar formation in vivo.


Long-chain cis-isoprenyltransferase activity is induced early in the developmental program for protein N-glycosylation in embryonic rat brain cells.
A large developmental increase in Glc3Man9-GlcNAc2-P-P-dolichol (Oligo-P-P-Dol) synthesis and protein N-glycosylation in primary cultures of embryonic rat brain cells has been reported previously. In vitro enzyme studies and metabolic labeling experiments now show that there is a coordinate induction of long-chain cis-isoprenyltransferase (IPTase) activity, an activity required for the chain-elongation stage of dolichyl monophosphate (Dol-P) biosynthesis de novo, and Oligo-P-P-Dol biosynthesis in embryonic rat brain. Different developmental patterns were observed for IPTase and beta-hydroxy-beta-methyl-glutaryl-CoA (HMG-CoA) reductase activity as well as Dol-P and cholesterol biosynthesis, indicating that these pathways are regulated independently in rat brain. Three separate experimental approaches provide evidence that the amount of Dol-P available in the rough endoplasmic reticulum (RER) is a rate-limiting factor in the expression of the lipid intermediate pathway. First, metabolic labeling experiments show that the biosynthesis of Dol-P is induced at the same time or just prior to the induction of Oligo-P-P-Dol biosynthesis. Second, the time of induction and rate of Oligo-P-P-Dol synthesis are accelerated when Dol-P is supplemented in the culture medium. Third, in vitro assays of mannosylphosphoryldolichol synthase and N-acetylglucosaminylpyrophosphoryldolichol synthase indicate that there are only minor increases in the levels of these enzymes during development, but the amount of endogenous Dol-P in the RER that is accessible to the glycosyltransferases increases when IPTase activity is induced. In summary, the current studies with embryonic rat brain cells document the coordinate induction of IPTase activity and Oligo-P-P-Dol synthesis, support the hypothesis that the availability of Dol-P in the RER is one rate-limiting factor in Oligo-P-P-Dol synthesis, and strongly suggest that increases in IPTase activity and the rate of de novo Dol-P biosynthesis enhance the capacity of embryonic rat brain cells for lipid intermediate synthesis early in the developmental program for N-linked glycoprotein biosynthesis.


Urban versus rural differences of hip fractures among the elderly in Kyoto, Japan: a 10-year study.
Secular changes in the incidence rate of hip fractures were estimated to vary by fracture type, i.e., femoral neck or trochanteric fractures, age, and sex, in urban or rural areas in Kyoto Prefecture, Japan from 2008 to 2017. Our survey in Kyoto Prefecture from 2008 to 2017 showed that the incidence rate of femoral neck fractures is generally increasing. We investigated the differences between urban and rural areas in the changes of the incidence rate over time of femoral neck and trochanteric fractures during the same period. Patients aged 65 years and above who sustained hip fractures between 2008 and 2017 and were treated at one of the participating 11 hospitals were included. The ratio of sick beds for acute-term care at the investigated hospitals to total number of beds in the urban area was 16.5% (1863/11,158) and 30.6% (1863/5623) in the rural area. The change in incidence rate was estimated utilizing the population according to the national census conducted in 2010 and 2015. There were 3559 and 6474 hip fractures in the urban and rural areas, respectively. Femoral neck fractures were 1936 (54.4%) and 2813 (43.5%) in each area. The increase of the population-adjusted numbers was marked by neck fractures in males, in both areas. In women, there was a significant increase in femoral neck fractures in the urban area in those aged 85 years and over. For trochanteric fractures, a significant increase was only found in women aged 65 to 74 years in the rural area. A regional difference in the secular changes in incidence rate of hip fractures was found in women, not in men, mostly because neck fractures in women increased in the over 85 group in the urban area.


A study on experimental characteristic of microwave-assisted pyrolysis of microalgae.
The microwave-assisted pyrolysis of Chlorella vulgaris was carried out under different microwave power levels, catalysts and contents of activated carbon and solid residue. The products, pyrolysis temperature and temperature rising rate were analyzed in order to obtain the optimal conditions. The results indicated that the higher the microwave power level was, the higher the maximum temperature rising rate and pyrolysis temperature were. The maximum bio-oil yield (35.83 wt.%) and gas yield (52.37%) were achieved under the microwave power of 1500 W and 2250 W, respectively. And 2250 W was the optimal power to obtain bio-fuel product. High microwave power level and catalyst can enhance the production of gas. Catalysts can promote the pyrolysis of C. vulgaris, and activated carbon was the best among the tested catalysts followed by the solid residue. The optimal content of activated carbon is 5% with the maximum bio-fuel yield of 87.47%.


Complete thoracoscopic enucleation of the esophageal leiomyoma at the level of the azygos vein: A case report.
Benign tumors of the esophagus are rare. Among them, leiomyomas are common. Surgical enucleation is indicated in cases, which have symptoms or large tumors. The enucleation through video assisted thoracoscopic surgery has been developed as a preferred approach for the majority of lesions in recent years. However, the complete thoracoscopic enucleation for an esophagus leiomyoma at the level of the azygos vein without cutting the vein and nor using artificial pneumothorax by CO2 insufflations is a challenge for thoracic surgeons. This case report was a 64-year-old female who presented dysphagia and chest pain. Chest computed tomography and esophageal endoscopy displayed an esophageal mass. We used complete thoracoscopic enucleation to treat this condition. The tumor was at the level of the azygos vein. Therefore, it was difficult to remove the tumor without cutting the azygos vein without utilizing the artificial pneumothorax. However, we enucleated it completely with no complications. The complete thoracoscopic enucleation of the esophageal leiomyoma at the level of the azygos vein without cutting the vein without using the artificial pneumothorax should be applied. A methylene blue swallowing study is an alternative method to a barrium swallowing study while the chest tube is still placed in the pleural space.


[Clinico-statistical considerations on a sample of school-age population in the Province of Trieste. II. Period of eruption of the second molars and change of the canines and 1st and 2d permanent premolars].
The phenomena relating to the period of change of the canines and the first and second permanent premolars and of the eruption of the second permanent molar were studied in a group of 343 Trieste school children. Both deciduous and permanent teeth were examined. The results were processed on a computer, and are presented in graph form.


Elevated levels of plasma homocysteine in postmenopausal women in Burkina Faso.
Low levels of plasma homocysteine have been found in children and adult populations living in Burkina Faso in association with a low prevalence of coronary heart disease. Based on this finding, the levels of plasma homocysteine and other thiols (cysteine, cysteinylglycine, glutathione) in postmenopausal women living in Burkina Faso were evaluated with the aim of investigating whether age and life conditions influence plasma homocysteine and other thiol levels. It was found that in older postmenopausal women the mean level of homocysteine was higher (16.4+/-6.6 micromol/L) than in fertile women (6.8+/-1.2 micromol/L) and that this increase was correlated with cysteine levels (166.6+/-44.6 micromol/L). While the glutathione level in postmenopausal women was lower (3.6+/-2.3 micromol/L) compared with fertile women (7.0+/-1.7 micromol/L), cysteinylglycine levels were within the normal range (29.9+/-9.3 micromol/L). No correlation was found between homocysteine levels and serum folate, vitamin B(12), vitamin B(6), cystatin C and serum creatinine levels. The older the women were, the higher were their plasma homocysteine levels: levels up to 20.2+/-9.1 micromol/L were found in those >70 years old. The elevated levels of homocysteine in the postmenopausal women of Burkina Faso must be viewed as a characteristic of older age and its metabolic consequences.


Regulation of histone gene transcription in yeast.
Histones are the primary protein component of chromatin, the mixture of DNA and proteins that packages the genetic material in eukaryotes. Large amounts of histones are required during the S phase of the cell cycle when genome replication occurs. However, ectopic expression of histones during other cell cycle phases is toxic; thus, histone expression is restricted to the S phase and is tightly regulated at multiple levels, including transcriptional, post-transcriptional, translational, and post-translational. In this review, we discuss mechanisms of regulation of histone gene expression with emphasis on the transcriptional regulation of the replication-dependent histone genes in the model yeast Saccharomyces cerevisiae.


Differences in membrane unsaturated fatty acids and electron spin resonance in different types of myeloid leukemia cells.
The fatty acid composition and some physical properties of intact cells and isolated plasma membranes of two types of mouse myeloid leukemia cell clone grown in culture have been examined. One clone type, MGI+D+, can be induced by the macrophage and granulocyte-inducing protein (MGI) to differentiate into mature macrophages and granulocytes. The other clone type, MGI+D-, could not be induced to differentiate into mature cells. A two-fold increase in the ratio of saturated fatty acid to unsaturated fatty acid was found in the MGI+D- compared to the MGI+D+ clones. The MGI+D- clones produced an unusual polyunsaturated C20:5 fatty acid at 28 degrees C, whereas the MGI+D+ clones did not grow at this temperature. The cells and their isolated plasma membranes were studied by electron spin resonance. The motion of the 5-nitroxide stearate spin label was found to be higher in the intact cells and in the membranes of MGI+D- clones than of the MGI+D+ clones. The cells of MGI+D+ clones showed a similar freedom of motion to normal myeloblasts from the bone marrow. The results indicate that myeloid leukemia cells which differ in their competence to be induced to differentiate into mature cells have different physical properties of their plasma membranes and that this is correlated with their fatty acid acyl chain composition.


IL-17A neutralization fails to attenuate airway remodeling and potentiates a proinflammatory lung microenvironment in diacetyl-exposed rats.
Bronchiolitis obliterans (BO) is a devastating lung disease that can develop following inhalation exposure to certain chemicals. Diacetyl (DA) is one chemical commonly associated with BO development when inhaled at occupational levels. Previous studies in rats have shown that repetitive DA vapor exposures increased lung CD4+CD25+ T cells and bronchoalveolar (BAL) interleukin-17A (IL-17A) concentrations concurrent with the development of airway remodeling. We hypothesized that IL-17A neutralization would attenuate the severity of airway remodeling after repetitive DA vapor exposures. Sprague-Dawley rats were exposed to 200 parts-per-million DA vapor or filtered air (RA) for 6 h/day × 5 days and monitored for 2 wk postexposure. Treatment with IL-17A neutralization (αIL-17A) or IgG (control) began immediately following exposures and continued twice weekly until study's end. Lungs were harvested for histology, flow cytometry, and BAL analyses. Survival, oxygen saturations, and percent weight change decreased significantly in DA-exposed versus RA-exposed rats, but did not differ significantly between DA + αIL-17A versus DA + IgG. Similarly, the number nor severity of airway lesions did not differ significantly between DA + αIL-17A versus DA + IgG rats despite the percentage of lung regulatory T cells increasing with decreased BAL IL-17A concentrations. Ashcroft scoring of the distal lung parenchyma suggested worse parenchymal remodeling in DA + αIL-17A versus DA + IgG rats with increased expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor-kappa B (NF-κB). Collectively, IL-17A neutralization in DA-exposed rats failed to attenuate airway remodeling with increased expression of pro-inflammatory cytokines TNF-α, IL-1β, and NF-κB.NEW & NOTEWORTHY Interleukin-17A (IL-17A) neutralization has shown benefit previously in preclinical models of transplant-associated bronchiolitis obliterans (BO), yet it remains unknown whether IL-17A neutralization has similar benefit for other forms of BO. Here, IL-17A neutralization fails to prevent severe airway remodeling in rats exposed repetitively to the flavoring chemical diacetyl, and instead, promotes a proinflammatory microenvironment with increased expression of TNF-α, IL-1β, and NF-κB within the lung.


Relevance of soluble cytotoxic factors generated by mycoplasma-contaminated targets to natural killer cell-mediated killing.
The possible involvement of soluble cytotoxic factors (SCF) in the lytic mechanism of natural killer (NK) cell-mediated cytotoxicity (CMC) was investigated. Tumor target cells (TC) were examined for their ability to stimulate the release of SCF from human peripheral blood lymphocytes (PBL). SCF were detected when effector cells (EC) were stimulated with mycoplasma-contaminated (MC)-TC and with concanavalin A (Con A), but mycoplasma-free (MF)-TC were unable to induce SCF. Pretreatment of EC with beta-interferon augmented the production of SCF with MC-K562 and Con A, but not with MF-K562. However, MF-K562 once infected with the culture supernatant from MC-K562, as well as mycoplasmas concentrated from culture supernatant, were able to induce SCF. Only Con A was capable of generating cytotoxic supernatants from EC that had been inactivated with MF-K562 and from EC depleted of Leu 11b positive cells. Moreover, when EC were evaluated for NK activity after coculture with MF-K562, their ability to kill fresh MF-K562 in the standard NK-CMC assay was greatly reduced. This loss of lytic potential was not accompanied by SCF release. Collectively, these data suggest that mycoplasma organisms play a crucial role in the induction of human SCF, and the implication that SCF, including NK cytotoxic factors (NKCF), are the lytic mediators in NK-CMC needs to be re-evaluated.


Neurological outcomes in adult drowning patients in China.
Drowning is the third leading cause of unintentional death worldwide. The epidemiological characteristics of adult drownings are rarely reported. Investigate factors associated with neurological prognosis in adult drowning inpatients. Multicenter medical record review. Tertiary health care institutions. We collected demographic and clinical data on patients who drowned but survived between September 2006 and January 2020. Neurological prognosis was compared in patients with and without cardiac arrest. Neurological outcomes. 142 patients with mean age of 50.6 (19.8) years, male/female ratio of 1.54:1. Forty-five patients (31.7%) received CPR, 90 patients (63.4%) experienced unconsciousness, and 59 patients (41.5%) received endotracheal intubation and mechanical ventilation. Multivariate logistic regression analysis showed that the initial blood lactic acid level (OR: 7.67, 95%CI: 1.23-47.82, P=.029) was associated with a poor neurological prognosis in patients without cardiac arrest. The incidence of ICU admission (OR: 16.604, 95%CI: 1.15-239.49, P=.039) was associated with a poor neurologic prognosis in patients with cardiac arrest. For the drowning patients with cardiac arrest, ICU admission was associated with neurological function prognosis in these patients. Among the patients without cardiac arrest, the initial lactate value was associated with neurological function prognosis of these patients. Retrospective. None.


A Rare Case of Constrictive Pericarditis: Inflammatory Myofibroblastic Tumor.
A previously healthy 15-year-old adolescent female presented with dependent edema, ascites, and dyspnea on exertion. The result of her initial evaluation was consistent with constrictive pericarditis in the setting of local low-grade spindle cell sarcoma. She was unresponsive to traditional medical management and required concurrent mass resection and radical pericardiectomy for definitive treatment. (Level of Difficulty: Intermediate.).


Nanotechnology Approaches for Increasing Nutrient Bioavailability.
Health-promoting ingredients such as phenolic compounds, vitamins, and minerals are being increasingly introduced into foods and beverages to produce "functional foods" specifically designed to improve human health, well-being, and performance. However, it is often challenging to incorporate these nutraceuticals into foods because they have poor solubility characteristics, impart undesirable flavor profiles, are chemically unstable, or have low bioavailability. This problem can often be overcome by encapsulating the bioactive components in nanoparticle-based delivery systems. The bioavailability of encapsulated bioactive agents often increases when the size of the particles containing them decreases, due to their faster digestion, ability to penetrate the mucus layer, or direct uptake by cells. Nanoparticles can be formulated to survive passage through specific regions of the gastrointestinal tract and then release their payload at a specified point, thus maximizing their potential health benefits. Nutraceutical-loaded nanoparticles can be fabricated through lipid formulations, natural nanocarriers, specialized equipment, biopolymer nanoparticles, and miscellaneous techniques. Classification into these five groups is based on the main mechanism or ingredient used to fabricate the nanoparticles. This chapter focuses on the utilization of food-grade nanoparticles for improving the performance of nutraceuticals in functional foods and beverages.


Toxicokinetics of the herbicide dichlorprop and its leucinate and their action on liver mixed function oxidase in rats.
The concentrations of dichlorprop and its leucine conjugate in serum and bile of rats have been determined at different periods after a single oral dosage of these compounds (30 or 300 mg/kg body weight). From the results it can be concluded that dichlorprop is excreted by active renal mechanisms resembling that described for 2,4,5-T. It is suggested that the leucinate is excreted more by the biliary route. Investigations of the liver demonstrate that both compounds are able to induce mixed function oxidases.


Rising StARs: behavioral, hormonal, and molecular responses to social challenge and opportunity.
Across taxa, individuals must respond to a dynamic social environment of challenges and opportunities on multiple biological levels, including behavior, hormone profiles, and gene expression. We investigated the response to a complex social environment including both territorial challenges and reproductive opportunities in the African cichlid fish Astatotilapia burtoni (Burton's mouthbrooder), a species well-known for its phenotypic plasticity. Male A. burtoni are either socially dominant or subordinate and can transition between the two phenotypes. We used this transition to simultaneously study changes in aggression, reproductive behavior, testosterone and estradiol levels, gonadal histology, and testes expression of three genes involved in testosterone synthesis. We have found that males immediately become aggressive and increase testosterone levels when they become dominant in this paradigm of challenge and opportunity. Reproductive behavior and estradiol increase slightly later but are also up-regulated within 24h. Increases in steroid hormone levels are accompanied by an increase in expression of steroidogenic acute regulatory protein (StAR), the rate-limiting enzyme during testosterone synthesis, as well as an increase in testis maturation as measured by histological organization. Reproductive behavior was found to correlate with female gravidity, suggesting that males were able to perceive reproductive opportunity. Our study demonstrates the rapid plasticity at multiple levels of biological organization that animals can display in response to changes in their complex social environment.


Automatic segmentation of cervical region in colposcopic images using K-means.
Colposcopy is an important imaging modality for the detection of cervical lesions. The analysis of colposcopic images, especially the effective segmentation of the cervical region, has important clinical value in clinical application. A cervical segmentation method based on the HSV color mode is proposed, which can divide and extract the cervical region in the medical and anatomical sense. Firstly, the histogram threshold method is used to analyze the histogram (Y) of the colposcopic image. In order to achieve the removal of the mirror reflection pretreatment operation in the colposcopy image. Secondly, the Preprocessed RGB images is used. Then, the colposcopic image is converted into the HSV color space, and the V component is extracted using the K-means algorithm. Finally, using the area filter to smooth the edge, the segmented cervical region can be obtained. In our study, 110 standard colposcopy images, which were tagged by experts, were tested and verified. The segmentation results were analyzed and compared using dice coefficients, Jaccard coefficients, structural segmentation accuracy specificity, sensitivity, positive predictive value, and negative predictive value. Our experimental results show that the accuracy, specificity and sensitivity of the method are 87.25%, 81.99% and 96.70%, respectively. The effectiveness of the method in clinical segmentation was verified. Our study has demonstrated that cervical regional segmentation of colposcopic images based on HSV color space using K-means has high clinical utility and can help medical specialists in the diagnosis of cervical cancer.


Studies on sickled erythrocytes provide evidence that the asymmetric distribution of phosphatidylserine in the red cell membrane is maintained by both ATP-dependent translocation and interaction with membrane skeletal proteins.
In order to study factors which are involved in maintenance of phosphatidylserine (PS) asymmetry within the human red cell membrane, we measured the effect of ATP-depletion and of membrane skeleton/lipid bilayer uncoupling induced by sickling on the distribution of PS within the membrane bilayer of sickle cells. Trace amounts of radiolabeled PS were introduced into the outer membrane leaflet of both fresh and ATP-depleted reversibly sickled cells (RSCs), using a non-specific lipid transfer protein purified from bovine liver. The equilibration of the newly introduced PS over the two halves of the bilayer was monitored by treatment of the cells with phospholipase A2 which selectively hydrolyzes only those molecules present in the outer membrane leaflet. Within 1 h after insertion into fresh RSCs, only 10% of the labeled PS was accessible to the action of phospholipase A2. This fraction was markedly increased when the cells were subsequently deoxygenated. Prolonged deoxygenation of RSCs, deprived of their ATP after incorporation of radiolabeled PS, caused enhanced phospholipase A2-induced hydrolysis of radiolabeled PS. Similarly, phospholipase A2-induced hydrolysis of endogenous PS in intact RSCs was markedly enhanced when ATP-depleted, but not when fresh cells, were incubated under nitrogen for 3.5 h. Deoxygenated ATP-depleted RSCs markedly enhanced the rate of thrombin formation in the presence of purified coagulation factors Xa, Va, prothrombin and Ca2+. This enhancement appeared to be dependent on the duration of incubation under nitrogen. This phenomenon, indicating the presence of increasing amounts of endogenous PS in the outer membrane leaflet, was not observed when either fresh RSCs or ATP-depleted normal erythrocytes were incubated under nitrogen. Our present observations provide evidence that, in addition to the interaction of PS with the skeletal proteins, an ATP-dependent translocation of PS is required to maintain its absolute asymmetric distribution in the human erythrocyte membrane.


Effect of olive oil consumption on cardiovascular disease, cancer, type 2 diabetes, and all-cause mortality: A systematic review and meta-analysis.
Some large prospective studies on olive oil consumption and risk of chronic disease suggested protective effects. We conducted an outcome-wide systematic review and meta-analysis of prospective cohort studies and randomized controlled trials (RCT) assessing the association between olive oil consumption and the primary risk of 4 different outcomes: cardiovascular disease (CVD), cancer, type 2 diabetes (T2D) or all-cause mortality through January 2022. Thirty-six studies were included in the systematic review and twenty-seven studies (24 prospective cohorts and 3 different reports from one RCT) were assessed in 4 quantitative random-effects meta-analyses. They included a total of 806,203 participants with 49,223 CVD events; 1,285,064 participants with 58,892 incident cases of cancer; 680,239 participants with 13,389 incident cases of T2D; and 733,420 participants with 174,081 deaths. Olive oil consumption was most frequently measured with validated food frequency questionnaires. Studies follow-up ranged between 3.7 and 28 years. A 16% reduced risk of CVD (relative risk [RR]: 0.84; 95% confidence interval [CI]: 0.76 to 0.94), standardized for every additional olive oil consumption of 25 g/d was found. No significant association with cancer risk was observed (RR: 0.94; 95% CI: 0.86 to 1.03, per 25 g/d). Olive oil consumption was associated with a 22% lower relative risk of T2D (RR: 0.78; 95% CI: 0.69 to 0.87, per 25 g/d) without evidence of heterogeneity. Similarly, it was inversely associated with all-cause mortality (RR: 0.89; 95% CI: 0.85 to 0.93, per 25 g/d). Only the results for T2D were homogeneous. Specific sources of heterogeneity for the other 3 outcomes were not always apparent. Prospective studies supported a beneficial association of olive oil consumption with CVD, T2D and all-cause mortality, but they did not show any association with cancer risk.


Alleviating depression in the unemployed: adequate financial support, hope and early retirement.
Results of a longitudinal study on older blue-collar workers in the Federal Republic of Germany (Soc. Sci. Med. 25, 173-178, 1987) showed that people who retired out of unemployment improve in depression similar to those people who found a job. Furthermore, financial problems and disappointed hope were important in the development of depression in the unemployed. These results are relevant for measures to alleviate depression in the unemployed in three areas: early retirement and an increase of financial unemployment compensation are recommended. Furthermore, all those programs (like counseling or therapeutic programs) that increase hope to find a job without increasing the chances to find a job have to be viewed with skepticism because they might actually turn out to be dysfunctional.


What factors interfere with the performance of preschool children in the language subtest of Bayley-III?
to verify if the performance of pre-school children born prematurely and at term in the Bayley-III language subtest differs and to identify whether variables gestational age, birth weight, socioeconomic level, and maternal education are determinant in the outcome of language development. Descriptive cross-sectional case-control study in which 36 pre-school children born prematurely and 27 born at term were evaluated concerning language development by the Bayley III subtest. Preschoolers between 18 and 36 months of chronological age were considered; with no syndromes or genetic, sensory, neurological, auditory, or visual impairments; and had not previously undergone speech therapy. Mann-Whitney, Fisher's Exact, and binary logistic regression tests were used for statistical analysis. the groups' performance did not differ either by the composite score (p = .701) or by the classification based on the percentile (p = .225). Gestational age, birth weight, and socioeconomic status did not influence the outcome of language development. However, maternal education was significant (p = .014) in the binary logistic regression model, suggesting that the mother having studied until basic education increases the chance of having a child underperforming in the Bayley III language subtest 6.31 times. there was no difference between the groups in the Bayley-III language subtest and only maternal education influenced the outcome of language development.


Donor-specific tolerance induction in composite tissue allografts.
Although prolonged composite tissue allograft (CTA) survival is achievable in animals using immunosuppressive drugs, long-term immunosuppression of CTAs in the clinical setting would be unacceptable for most patients. The purpose of this study was to develop a model for reliable CTA tolerance induction in the adult rat across a strongly antigenic MHC mismatch without the need for long-term immunosuppression. Chimeras were prepared using rat strains with strong MHC incompatibility [WF (RT1Au) + ACI (RT1Aa) --> WF, n = 13]. Syngeneic (WF) and allogeneic (ACI) bone marrow (BM) was harvested and T-cell depleted. Following confirmation of T-cell depletion by flow cytometry, a mixture of T-cell depleted syngeneic and allogeneic BM was injected into the recipient animals (all recipients pretreated with low-dose irradiation, 500 to 700 cGy). In addition, the recipient animals received a single dose of ALS (10 mg) 5 days prior to bone marrow transplantation (BMT) and tacrolimus (1 mg/kg/day) from the day prior to BMT to 10 days postoperatively. Rat chimeras were characterized by flow cytometry at 3 and 12 months after BM reconstitution and following hindlimb transplantation. Peripheral blood lymphocyte chimerism (WF/ACI) remained stable >12 months after BM reconstitution in 10 of 13 animals. Multilineage chimerism of both lymphoid and myeloid lineages was present, suggesting that engraftment of the pluripotent rat stem cell had occurred. In animals with donor chimerism >60%, there was no sign of limb rejection for the duration of the study. All animals with chimerism <20% developed moderate signs of rejection clinically and histologically. Gross motor and sensory reinnervation (weight bearing, toe spread) occurred at >60 days in 6 of 9 rats. Postoperative flow cytometry studies demonstrated stable chimerism in all animals studied (n = 7). Stable mixed allogeneic chimerism can be achieved in a rat hindlimb model of composite tissue allotransplantation. Hindlimb allografts to mixed allogeneic chimeras exhibit prolonged, rejection-free survival. This represents the first reliable model demonstrating rejection-free CTA survival in an adult animal without the long-term use of immunosuppressive agents across a strongly antigenic MHC mismatch.