Effects of methoxypoly (Ethylene glycol) mediated immunocamouflage on leukocyte surface marker detection, cell conjugation, activation and alloproliferation.
Tissue rejection occurs subsequent to the recognition of foreign antigens via receptor-ligand contacts between APC (antigen presenting cells) and T cells, resulting in initialization of signaling cascades and T cell proliferation. Bioengineering of donor cells by the covalent attachment of methoxypolyethylene glycol (mPEG) to membrane proteins (PEGylation) provides a novel means to attenuate these interactions consequent to mPEG-induced charge and steric camouflage. While previous studies demonstrated that polymer-mediated immunocamouflage decreased immune recognition both in vitro and in vivo, these studies monitored late events in immune recognition and activation such as T cell proliferation. Consequently little information has been provided concerning the early cellular events governing this response. Therefore, the effect of PEGylation was assessed by examining initial cell-cell interactions, changes to activation pathways, and apoptosis to understand the role that each may play in the decreased proliferative response observed in modified cells during the course of a mixed lymphocyte reaction (MLR). The mPEG-modified T cells resulted in significant immunocamouflage of lymphocyte surface proteins and decreased interactions with APC. Furthermore, mPEG-MLR exhibited decreased NFκB pathway activation, while exhibiting no significant differences in degree of cell death compared to the control MLR. These results suggest that PEGylation may prevent the direct recognition of foreign alloantigens by decreasing the stability and duration of initial cell-cell interactions.


[Predictors of malignancy in the management of parotid tumors: about 76 cases].
Salivary gland tumor pathology is complex and poses a diagnostic and therapeutic problem. A good analysis of predictive factors for malignancy in parotid tumors seems currently necessary for better therapeutic planning. The aim of this study was to investigate the predictive factors for malignancy in parotid tumors through a retrospective study of 76 cases of parotid tumor treated in a service of Otorhinolaryngology and Cervico Facial Surgery of Avicenne military hospital of Marrakech between January 2000 and December 2012. The study involved 40 women and 36 men. The average age was 44 years for benign tumours whereas it was 50 years for malignant tumours. The median of consultation time was 24 months for benign tumors and 16 month for malignant tumours. Swelling in the area of the parotid was always a patient detecting sign. Malignancy is clinically suspected based on pain, facial paralysis, surface structure and deeper structure fixity and on the presence of adenopathy. MRI has become the methodology of choice for evaluating parotid tumors due to its good diagnostic value in the assessment of benignity and malignancy. Fine needle aspiration biopsy has no value unless it is positive. Explorative parotidectomy with extemporaneous anatomopathological examination remains the key to positive diagnosis. Parotid benign tumors represent the most frequent entity (80%) and pleomorphic adenoma remains the predominant histologic type (61%). With regard to malignant tumors, they are rare, mainly dominated by mucoepidermoid carcinomas (6,5%). Surgical treatment is the first choice and it is often associated with lymph node dissection and radiation therapy for malignant tumors. Facial paralysis is the most common complication of parotid surgery.


Overview of Dorsal Preservation Rhinoplasty.
Renewed interest in dorsal preservation rhinoplasty (DPR) stems from theoretic esthetic and functional advantages over conventional hump resection. DPR fundamentally consists of en bloc dorsal lowering via a combined septal resection and mobilization of the bony pyramid. Several technical modifications exist, allowing for the expansion of DPR indications. Although studies suggest success with these techniques, comparative data to conventional hump resection are limited. Challenges and stigmata of DPR include a radix step-off, hump recurrence, supratip saddling, and widening of the midvault. The fusion of structural techniques with preservation ideology will facilitate the incorporation of DPR into clinical practice.


Dipstick enzyme immunoassay for rinderpest antibody in cattle.
A dipstick enzyme immunoassay (ELISA) has been standardized for the detection of rinderpest antibodies. One hundred and thirty bovine serum samples were analysed by the dipstick ELISA method and the results compared with the conventional plate ELISA method. The sensitivity was found to be similar in both methods. The dipstick ELISA does not require expensive micro-plates and an ELISA reader, and is recommended for use in field laboratories where the qualitative detection of rinderpest antibodies is required.


Acid Etching Strategy: Optimizing Bifunctional Activities of Metal/Nitrogen-doped Carbon Catalysts for Efficient Rechargeable Zn-Air Batteries.
Transition metal-embedded heteroatom carbon composites are regarded as an important branch of bifunctional catalysts for rechargeable Zn-air batteries. The inevitable transition metal particles on the carbon skeleton may affect the availability of the metal-heteroatom-carbon catalytic site. Herein, we propose an acid treatment strategy to remove the bare transition metal particles, thus regulating the electrochemical surface area. The OER activities are highly related to the electrochemical surface area for the catalysts with different acid treatment times. In addition, there exists an optimal acid treatment time to achieve the highest ORR and OER activities with the ΔE value of 0.75 V. Given the superior bifunctional activities after acid treatment, we further assemble the rechargeable Zn-air batteries with the optimal catalyst, which achieves a peak power density of 364 mW cm-2 and long cycling life of 500 h at 10 mA cm-2 . This work affords an efficient strategy to enhance the ORR/OER activities and may guide the design of transition metal/heteroatom carbon composites.


Development, Implementation, and Evaluation of a Pilot Parenting Educational Intervention in a Pregnancy Buprenorphine Clinic.
We developed a pilot evidence-based prenatal educational intervention to increase knowledge of neonatal abstinence syndrome (NAS) and early parenting skills for women with opiate dependency who enrolled in a pregnancy buprenorphine clinic. We developed, implemented, and tested modules regarding expectations during newborn hospitalization for observation or treatment of NAS and regarding evidence-based parenting skills in response to NAS behaviors. Testing evaluated baseline knowledge of early parenting skills with newborns at risk for NAS and change from baseline after the educational intervention. No statistically significant difference in composite knowledge scores was observed. A brief survey completed by the participants postpartum affirmed the perception of women that the educational intervention effectively prepared them for the early postpartum period while their newborns were hospitalized.


Evaluation of the Effectiveness of Probiotic Mouthwashes in Reducing Dental Plaque in Primary and Permanent Teeth: A Randomized Clinical Trial.
Due to the disadvantages of chemical mouthwashes, the search for an effective and safe anti-plaque agent has led to the emergence of probiotics. To compare the effectiveness of nonchemical mouthwashes (probiotic) with chemical mouthwashes (fluoride) on plaque accumulation in orphan children after seven, 14, and 30 days of use. The present study was a triple-blind randomized controlled trial with two parallel groups (A and B), which included 30 healthy children. Each group included 15 children aged between eight and 10 years from Dar Al-Rahma Orphanage in Damascus, Syrian Arab Republic. Group A used 10 ml of probiotic mouthwash (ProbioClean) and group B used 10 ml of fluoride mouthwash (Colgate) for 60 seconds for 30 days. Turesky Modified Quigley-Hein (TMQH) plaque index was used in this study to record the values of plaque accumulation on days seven, 14, and 30. Mann-Whitney U test showed statistical significance between probiotics and fluoride mouthwashes on days 14 (p < 0.001) and 30 (p = 0.001), and there was no statistical significance on day seven (p = 0.934). According to the results of this study, probiotic mouthwashes are considered an effective solution for maintaining oral health. However, probiotics are more effective in reducing plaque accumulation after a month of use.


Impact of ultrasound speed choice on the quality of the second-trimester fetal ultrasound examination in obese women.
The purpose of this study was to assess the impact of the free choice of ultrasound propagation velocity on ultrasound image construction to improve the completion rate and anatomical quality of fetal second-trimester ultrasound examination in obese women. This repeated cross-sectional single-center study retrospectively collected second-trimester ultrasound images of 88 obese women. During the first period, ultrasound examinations were performed in 44 women (mean age, 31.4±5.9 [SD] years; range: 21.1 - 45.3 years) applying only the standard 1540m/s tissue ultrasound velocity (group 1). During the second period, ultrasound examinations were performed in other 44 women (mean age, 31.4±5.1 [SD] years; range: 20.6 - 41.6 years) with the operator free to choose among three available velocity settings (1420m/s, 1480m/s or 1540m/s) for the scanning planes for the morphological images (group 2). All women underwent mid-trimester ultrasound examination at 20 to 24 gestational weeks. Two observers assessed the examinations in both groups for completeness, quality, and duration of fetal ultrasound examinations. No differences in age (P>0.99), body mass index (P=0.67), prevalence of previous cesarean delivery (P=0.30) or gestational age at the second-trimester scan (P=0.20) were found between the two groups. The mean cumulative duration of these ultrasound examinations was longer in group 1 than in group 2 (for both the complete (P=0.04) and incomplete (P=0.03) examinations). The quality of the anatomic images according to Salomon's criteria was less often acceptable in group 1 (5/44, 11.4%) than in group 2 (15/44, 34.1%) (P=0.02). Free choice of ultrasound velocity improves the overall performance of fetal second-trimester ultrasound examinations in obese women.


Loss of single HLA class I allospecificities in melanoma cells due to selective genomic abbreviations.
Expression of human leucocyte antigen (HLA) Class I molecules is essential for the recognition of malignant melanoma (MM) cells by CD8(+) T lymphocytes. A complete or partial loss of HLA Class I molecules is a potent strategy for MM cells to escape from immunosurveillance. In 2 out of 55 melanoma cell cultures we identified a complete phenotypic loss of HLA allospecificities. Both patients have been treated unsuccessfully with HLA-A2 peptides. To identify the reasons underlying the loss of single HLA-A allospecificities, we searched for genomic alterations at the locus for HLA Class I alpha-chain on chromosome 6 in melanoma cell cultures established from 2 selected patients with MM in advanced stage. This deficiency was associated with alterations of HLA-A2 gene sequences as determined by polymerase chain reaction-sequence specific primers (PCR-SSP). Karyotyping revealed a chromosomal loss in Patient 1, whereas melanoma cell cultures established from Patient 2 displayed 2 copies of chromosome 6. Loss of heterozygosity (LOH) using markers located around position 6p21 was detected in both cases. By applying group-specific primer-mixes spanning the 5'-flanking region of the HLA-A2 gene locus the relevant region was amplified by PCR and subsequent sequencing allowed alignment with the known HLA Class I reference sequences. Functional assays using HLA-A2-restricted cytotoxic T-cell clones were performed in HLA-A2 deficient MM cultures and revealed a drastically reduced susceptibility to CTL lysis in HLA-A2 negative cells. We could document the occurrence of selective HLA-A2 deficiencies in cultured advanced-stage melanoma metastases and identify their molecular causes as genomic alterations within the HLA-A gene locus.


Factors affecting long-term survival of horses recovering from surgery of the small intestine.
Epiploic foramen entrapment (EFE) has been associated with a particularly poor post operative prognosis for equine colic cases, but the reasons for this are unknown. To identify variables associated with post operative survival following surgery for small intestinal disease; develop a model describing long-term post operative survival; and identify reasons for the poor prognosis associated with EFE. Data from 382 horses undergoing surgery were used to identify variables associated with survival. A multivariable Cox proportional hazards model for post operative survival was developed and model fit evaluated. The final model included the variables total plasma protein (TP) and packed cell volume (PCV) at admission, duration of surgery and the dichotomous variable relaparotomy (yes/no). Risk of death was positively associated with increasing PCV, but negatively associated with increasing TP (which decreased the probability of death). In a univariable model, EFE cases had a significantly higher death rate than other types of small intestinal disease (hazard ratio = 1.7, P = 0.035). Multivariable modelling indicated that some of the increased risk associated with EFE cases was due to lower TP values and longer duration of surgery. Preoperative TP is associated negatively with the risk of post operative death in horses recovering from small intestinal surgery. Other variables associated with the probability of survival are preoperative PCV, duration of surgery and relaparotomy. The increased post operative death rate of EFE cases can be explained in part by lower TP and longer surgery times of these cases. Total plasma protein may be not simply a measure of hydration status in small intestinal colic cases, but an important determinant of survival. Further investigation of this relationship is warranted. Our model for post operative survival highlights the importance of preoperative TP, PCV and duration of surgery as prognostic indicators. This information should allow a more accurate post operative prognosis following small intestinal surgery.


Survival of infants and children born with severe microcephaly, Texas, 1999-2015.
Severe microcephaly is a brain reduction defect where the delivery head circumference is <3rd percentile for gestational age and sex with subsequent lifelong morbidities. Our objective was to evaluate survival among 2,704 Texas infants with severe microcephaly delivered 1999-2015. Infants with severe microcephaly from the Texas Birth Defects Registry were linked to death certificates and the national death index. Survival estimates, hazard ratios (HR) and confidence intervals (CI) were calculated using the Kaplan-Meier method and Cox proportional hazards models stratified by presence versus absence of co-occurring defects. We identified 496 deaths by age 4 years; most (42.9%) occurred in the neonatal period, and another 39.9% died by 1 year of age. Overall infant survival was 84.8%. Lowest infant survival subgroups included those with chromosomal/syndromic conditions (66.1%), very preterm deliveries (63.9%), or co-occurring critical congenital heart defects (44.0%). Among infants with severe microcephaly and a chromosomal/syndromic co-occurring defect, the risk of death was nearly three-fold higher among those with: proportionate microcephaly (i.e., small baby overall), relative to non-proportionate (HR = 2.84, 95% CI = 2.17-3.71); low-birthweight relative to normal (HR = 2.72, 95% CI = 1.92-3.85); critical congenital heart defects (CCHD) relative to no CCHD (HR = 2.90, 95% CI = 2.20-3.80). Trisomies were a leading underlying cause of death (27.5%). Overall, infants with severe microcephaly had high 4-year survival rates which varied by the presence of co-occurring defects. Infants with co-occurring chromosomal/syndromic anomalies have a higher risk of death by age one than those without any co-occurring birth defects.


DANAMIC: Data analyzer of minimum inhibitory concentrations - Protocol to analyze antimicrobial susceptibility data.
This protocol describes an open-source software developed to analyze experimental data obtained using antimicrobial susceptibility assays. We first describe experimental procedures for testing the activity of antimicrobial agents in vitro based on reference standards (BS EN ISO 20776-1:2020). We then describe the software protocol to analyze and convert the data obtained using these procedures into minimum inhibitory concentrations. This approach enables automated data analysis for microdilution assays and can be adapted for high-throughput antimicrobial screening.


Effect and mechanism of the CACNA2D1-CGRP pathway in osteoarthritis-induced ongoing pain.
This study built an OA model in rats by monosodium iodoacetate (MIA) injection to determine the effects and mechanism of the voltage-dependent calcium channel subunit alpha-2/delta-1 (CACNA2D1)-calcitonin gene-related protein (CGRP) pathway in osteoarthritis (OA)-induced ongoing pain. CACNA2D1 expression was measured by qPCR assay, western blotting assay, and immunofluorescence. Pain behaviors in rats were assessed with the measurement of thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT). The expression of CACNA2D1, neuropeptide Y (NPY), activating transcription factor 3 (ATF3), CGRP, protein kinase A (PKA), phosphorylated (p)-PKA, adenylyl cyclase (AC), protein kinase C (PKC), p-PKC, phospholipase C (PLC), and mitogen-activated protein kinase (MAPK) signaling pathway proteins were measured, OA rats had higher CACNA2D1 expression than normal rats. Knockdown of CACNA2D1 led to the elevation of the pain threshold of OA rats, and CACNA2D1 over-expression decreased the pain threshold of normal rats. Moreover, CACNA2D1 over-expression inhibited the expression of CGRP, up-regulated the expressions of NPY, ATF3, p-PKA, AC, p-PKC, PLC, p-Jun N-terminal kinase (JNK), and p-p38, and had no significant effect on phosphorylated extracellular signal-regulated kinase (p-ERK) expression in vivo and in vitro. Using this model of MIA-induced OA, we demonstrated that CACNA2D1 might be involved in the process of pain by modulating the CGRP and AC-PKA/PKC/MAPK signaling pathways in the dorsal root ganglion.


The treatment of chronic sinusitis: a controversial issue.
The persistence of sinusitis after upper respiratory tract infection is influenced by a range of aetiological factors such as anatomical variation which may be surgically corrected, mucociliary abnormalities and immune deficiency. The latter is more common than previously realised, encompassing IgG subclass deficiency, reduced opsonization and Fc gamma receptor polymorphism. This has therapeutic implications, with the possibility of IgG replacement therapy and vaccination. CT scanning suggests that the age of the patient and anatomical abnormalities are important aetiological factors in chronic rhinosinusitis. Only when medical therapy fails, is surgery considered. Although a range of surgical procedures are available, an endoscopic approach may be directed at the ostiomeatal complex and is generally very conservative. Scanning is a prerequisite to this surgery, demonstrating both the extent of disease and the anatomy but requires careful interpretation. Furthermore, an endoscopic technique can be employed for a number of other sinus conditions though this should only be undertaken by an experienced surgeon. A long-term prospective study of children undergoing radical sinus surgery for neoplasia strongly suggests that concerns that surgery in the middle meatus might disturb subsequent facial development are unfounded.


Relationship between science and technology.
Do economic advances spring directly from fundamental scientific discoveries? The early history of the transistor suggests that the situation is not nearly so simple as this.


Oxygen dependency of germinating Brassica seeds.
Establishing plants in space, Moon or Mars requires adaptation to altered conditions, including reduced pressure and composition of atmospheres. To determine the oxygen requirements for seed germination, we imbibed Brassica rapa seeds under varying oxygen concentrations and profiled the transcription patterns of genes related to early metabolism such as starch degradation, glycolysis, and fermentation. We also analyzed the activity of lactate dehydrogenase (LDH) and alcohol dehydrogenase (ADH), and measured starch degradation. Partial oxygen pressure (pO2) greater than 10% resulted in normal germination (i.e., protrusion of radicle about 18 hours after imbibition) but lower pO2 delayed and reduced germination. Imbibition in an oxygen-free atmosphere for three days resulted in no germination but subsequent transfer to air initiated germination in 75% of the seeds and the root growth rate was transiently greater than in roots germinated under ambient pO2. In hypoxic seeds soluble sugars degraded faster but the content of starch after 24 h was higher than at ambient oxygen. Transcription of genes related to starch degradation, α-amylase (AMY) and Sucrose Synthase (SUS), was higher under ambient O2 than under hypoxia. Glycolysis and fermentation pathway-related genes, glucose phosphate isomerase (GPI), 6-phosphofructokinase (PFK), fructose 1,6-bisphosphate aldolase (ALD), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate decarboxylase (PDC), LDH, and ADH, were induced by low pO2. The activity of LDH and ADH was the highest in anoxic seeds. Germination under low O2 conditions initiated ethanolic fermentation. Therefore, sufficient oxygen availability is important for germination before photosynthesis provides necessary oxygen and the determination of an oxygen carrying capacity is important for uniform growth in space conditions.


Probiotic Enterococcus faecalis AG5 mitigated high fat diet induced obesity and produced propionic acid stimulated apoptosis in 3T3-L1 pre-adipocyte.
Probiotics and their metabolites (SCFA) can regulate energy homeostasis. The present study thus evaluates the synergistic effect of probiotic Enterococcus faecalis AG5 on HFD induced obesity and the role of propionic acid (PA) in apoptosis induction of 3T3-L1 pre-adipocyte. Male Wistar rats (n = 24) were used to develop an HFD induced obesity model for 24 weeks. The effect of the orally administered probiotic AG5 (18th-24th weeks, 1 × 109 CFU/ml) was evaluated using physiological, biochemical, anthropometry, histopathological and serological analyses. Apoptosis in 3T3-L1 pre-adipocyte was assessed using flow cytometry, protein expression of PPARγ, 5-LOX, NF-κB, p-AKT, caspase 10 and detection of caspase 3/7 by Immunofluorescence confirmed the apoptosis induced by PA. Probiotic AG5 significantly reduced body weight, BMI, serum cholesterol, triglycerides (p < 0.05) and improved HDL, insulin and leptin but lowered LDL and VLDL (p > 0.05). An inflammatory response was reduced as evident by TNF-α IHC. AG5 reduced adipocyte hypertrophy and fatty acid accumulation. Flow cytometry confirmed late apoptosis in PA-AG5 and standard PA treated 3T3-L1 cells. 5-LOX inhibition is associated with apoptosis induction, and increased caspase 1p 10 is related to cell death initiation. The study initially showed a low PPARγ activity inhibiting 5-LOX which may relate to adipose apoptosis. Finally caspase 3/7 detection using immunofluorescence proved the role of PA in adipocyte apoptosis. The present study is a novel approach towards obesity mitigation involving adipocyte apoptosis. The role of SCFA in adipocyte apoptosis is very limited which can prove to be novel therapeutic approach in the future.


Preconditioning by inhaled nitric oxide prevents hyperoxic and ischemia/reperfusion injury in rat lungs.
Since the generation of nitric oxide (NO) is an essential step in the trigger phase of ischemic preconditioning, short-term inhalation of NO before ischemia should ameliorate ischemia/reperfusion (I/R) injury of the lung. We tested this hypothesis in high oxygen (>99%) ventilated rats in order to additionally evaluate compatibility of NO and exposure to hyperoxia. Male adult Sprague-Dawley rats inhaled NO (15 ppm, 10 min) before the left lung hilum was clamped for 1 h, and the reperfusion phase was observed for 4 h (NO group). Animals in the I/R group underwent the same treatment, but without NO inhalation. A third group without I/R served as time-matched controls. Animals in the I/R group showed severe I/R injury in terms of arterial pO2 (apO2), which was reduced to 22% of surgical controls (SCs) at time point 30 min reperfusion, and increased endothelial permeability (Evans blue procedure). The pretreatment with NO attenuated these effects. The pO2 after 4 h reperfusion was still 3.0-fold higher in the NO group compared to I/R. In contrast, the I/R- and hyperoxia-induced invasion of leukocytes, as determined by measuring myeloperoxidase (MPO) activity, was not affected by NO. These data were correlated with the activity of major cellular signaling pathways by measuring the phosphorylation at activating and inhibitory sites of extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, protein kinase B (AKT), and glycogen synthase kinase 3beta (GSK-3beta), and by determination of cGMP in plasma and lung tissue. Inhalation of NO partly prevented the loss of activation by I/R and hyperoxic ventilation of ERK, JNK, and AKT, and it reduced the I/R-induced activation of GSK-3beta. The level of cGMP in plasma and lung tissue was increased in the NO group after 4 h reperfusion. In conclusion, application of inhaled NO in the preconditioning mode prevented I/R injury in the rat lung without interfering effects of hyperoxic ventilation. The effects of NO on cellular signaling pathways resemble mechanisms of ischemic preconditioning, but further studies have to evaluate the physiological relevance of these results.


Under greater cooperative care, childhood fear is more accommodated, but less warranted.
The target article posits that caregiver cooperation rendered heightened expression of childhood fear an adaptive response to threat. I argue that caregiver cooperation rendered childhood fear expression less accurate as a signal of actual threat, and hence less effective for harm avoidance. Further, other emotional expressions that avoid unwarranted caregiver stress may be more likely to evoke needed care.


An analysis of the Gene-Tox Carcinogen Data Base.
The Gene-Tox Carcinogen Data Base is an evaluated source of cancer data on 506 chemicals selected in part for their previous assessment in genetic toxicology bioassays. This data base has been analyzed for the distribution of these chemicals into chemical classes. The major chemical classes (6% or greater of the total data base) are: acyl-, alkyl-, and aryl-halides; alcohols and phenols; aliphatic and aromatic amines, amides, and sulfonamides; benzene-ring-containing chemicals; organo-lead, -mercury, -phosphorous compounds, metals and derivatives, phosphoric acid esters, and phosphoramides; and polycyclic aromatic hydrocarbons. Cancer studies representing a subset of the Gene-Tox Carcinogen Data Base, 199 chemicals which were rated as Sufficient Positive/Negative or Limited Positive/Negative, were examined for distribution of those studies by animal species, gender, route of chemical administration, duration of study, major tumor sites, and major tumor types. These analyses revealed that the Gene-Tox Carcinogen Data Base contains a large number of lifetime studies involving the rat and mouse treated by oral routes of administration. The major organs that were targets were: liver, lung, skin, forestomach, bladder, and mammary gland, while the major tumor types were: carcinoma, sarcoma, papilloma, and adenoma. Chemicals in the data base have been assessed for species-specific carcinogenic effects, and these results indicate that for mice and rats there is a high correspondence (85%). This number is higher than that (71%) reported by Tennant et al. (1986) based on the recent results of 72 chronic cancer bioassays performed by the National Toxicology Program. This difference is probably based on the nature of the chemicals selected for inclusion in both data bases. Although the absolute value of this correspondence is unknown, it would seem to be within this range. When chemicals in the Gene-Tox Carcinogen Data Base were examined for their previous evaluation in 73 genetic toxicology bioassays, only 26 of these bioassays had 30 or more chemicals. In these 26 bioassays, the prevalence of positive chemicals was generally greater than 80-90%. This suggests that a thorough evaluation of genetic toxicology bioassays in regard to their ability to predict carcinogenic effects in animals is premature at this time.


Effects of succinylcholine at the masseter and adductor pollicis muscles in adults.
The effect of succinylcholine on baseline tension and evoked twitch height was measured at the masseter and the adductor pollicis muscles in ten adults undergoing elective surgery. During thiopental-nitrous oxide-enflurane (end-tidal concentration less than 0.25%) anesthesia, supramaximal stimulation was applied to both the ulnar nerve and the nerve to the masseter. Baseline tension and the isometric force of contraction were measured at the jaw and the thumb. Cumulative dose-response relationships were obtained by giving succinylcholine in incremental doses (initial dose, 0.10 mg/kg, followed by 0.05- or 0.1-mg/kg increments, depending on response). An infusion was started after the maximum effect of the first dose, at a rate adjusted to compensate for the rapid metabolism of the drug. There was no difference between the sensitivity of the masseter and the adductor pollicis. The ED50 values were (mean +/- SEM) 0.11 +/- 0.01 mg/kg at both muscles. The ED90 values were 0.17 +/- 0.02 mg/kg at the masseter and 0.16 +/- 0.01 mg/kg at the adductor pollicis. Onset of action was more rapid at the masseter. In six of the ten patients, baseline tension at the jaw was found to increase by a mean of 80 +/- 24 g (range 25-188 g). It is concluded that in adults, masseter neuromuscular blockade can be achieved with succinylcholine doses approximately equal to those required to block the adductor pollicis. In addition, the drug may cause increased tension in the muscles of the jaw.


In vitro labeling of proteins by reductive methylation: application to proteins involved in supramolecular structures.
Actin and tropomyosin, purified from both muscle and brain, and alpha-actinin, purified from muscle, have been labeled in vitro by reductive methylation to specific activities of greater than 10(5) dpm/micrograms protein. Actin so modified bound DNase I and polymerized identically to unmodified actin. Furthermore, the spectral properties of actin did not change after labeling. The interactions of labeled tropomyosin and alpha-actinin with F-actin were nearly identical to those of the unmodified proteins. These modified proteins comigrated with their unmodified counterparts in both SDS-containing polyacrylamide gels and isoelectric focusing gels. The labeled actin was quantitatively extracted from SDS-containing polyacrylamide gels (yield greater than 98% of radioactivity applied demonstrating that all of the radioactivity was protein bound. The reductive methylation procedure worked well at pH 8.0-8.5 in either pyrophosphate buffer or Bicine buffer using formaldehyde with [3H]-sodium borohydride as the reducing agent. The procedure could also be performed at pH 7.0 in phosphate buffer using (14C]-formaldehyde with sodium cyanoborohydride as the reducing agent. Proteins so labeled are ideal for use in quantitative experiments involving protein-protein interactions.


Using rice to understand the origin and amplification of miniature inverted repeat transposable elements (MITEs).
Recent studies of rice miniature inverted repeat transposable elements (MITEs), largely fueled by the availability of genomic sequence, have provided answers to many of the outstanding questions regarding the existence of active MITEs, their source of transposases (TPases) and their chromosomal distribution. Although many questions remain about MITE origins and mode of amplification, data accumulated over the past two years have led to the formulation of testable models.


Appointment scheduling and cost in first opinion small animal practice.
Approximately half of first opinion, small animal consultations exceed their allocated time and there's a growing call in the UK for longer consults. The aim of this study was to investigate and describe allocated appointment length in first opinion, small animal practice in the UK. Almost half (49.8%) of consults were scheduled for 15 min, with a further 39.4% scheduled for 10 min. Nearly all participants (97.1%) reported flexibility when booking appointments, scheduling longer appointments for conditions predicted to require more time. However, the majority (68.1%) reported no additional cost charged to the client for a longer consult. Furthermore, 54.7% of the survey respondents offered nurse appointments free of charge. A restructured approach to consult scheduling for both Veterinary Surgeon and Registered Veterinary Nurse (RVN) consultations could help to improve workforce wellbeing, utilise the vast knowledge and skill sets of RVNs and improve financial metrics.


Full regeneration of descending corticotropin-releasing hormone axons after a complete spinal cord injury in lampreys.
Sea lampreys are a vertebrate model of interest for the study of spontaneous axon regeneration after spinal cord injury (SCI). Axon regeneration research in lampreys has focused on the study of giant descending neurons, but less so on neurochemically-distinct descending neuronal populations with small caliber axons. Corticotropin-releasing hormone (CRH) is a neuropeptide that regulates the stress response or locomotion. CRH is also a neuropeptide of interest in the SCI context because descending CRHergic projections from the Barrington's nucleus control micturition behavior in mammals. Recent work from our group revealed that in sea lampreys the CRHergic innervation of the spinal cord is only of descending origin. Thus, the lack of intrinsic CRH spinal cord neurons provides the opportunity to analyze the regeneration of this descending system by using immunofluorescence methods. Here, we used an antibody against the sea lamprey mature CRH peptide, confocal microscopy, lightning adaptive deconvolution, and ImageJ to analyze the regenerative capacity of the descending CRH-immunoreactive (-ir) axons of larval sea lampreys after a complete SCI at the level of the fifth gill. At 10 weeks post-lesion, when behavioral analyses showed that injured animals had recovered normal appearing locomotion, our results revealed a full recovery of the number of CRH-ir profiles (axons) at the level of the sixth gill. Thus, the CRH descending axons of lampreys fully regenerate after a complete SCI. Our study provides a new model to study spontaneous and successful axonal regeneration in a specific neuronal type with small caliber axons by using simple immunohistochemical methods.


Enhanced intake of high-fat food following striatal mu-opioid stimulation: microinjection mapping and fos expression.
Our previous studies have shown that stimulation of mu-opioid receptors within the nucleus accumbens preferentially enhances intake of palatable food containing sucrose and fat; thus, opioids in this brain area may mediate the rewarding characteristics of food by modulating taste and macronutrient preference. The present study was designed to further explore the nature of the involvement of striatal opioids in feeding behavior, such as the location of sensitive subregions of the ventral striatum and the brain neural circuits involved in opioid-mediated hyperphagia. In Experiment 1, we conducted a microinfusion mapping study of feeding behavior by microinfusion of the mu receptor agonist, D-Ala(2),NMe-Phe(4), Glyol(5)-enkephalin (0, 0.025 and 0.25 microg/0.5 microl per side; equivalent to 0, 0.04 and 0.40 nmol/0.5 microl per side), into several striatal subregions. In Experiment 2, detection of the expression of the immediate early gene, c-fos, was used to examine brain areas activated following intra-striatal microinfusion of D-Ala(2), NMe-Phe(4),Glyol(5)-enkephalin. The microinjection mapping study demonstrated a broad anatomical gradient within the striatum, with sensitivity highest in relatively more lateral and ventral regions of the striatum (ventrolateral striatum, lateral shell and core). The Fos mapping study demonstrated that circuitry including hypothalamic areas, the ventral tegmental area, the substantia nigra and the nucleus of the solitary tract was recruited by stimulation of mu receptors within the nucleus accumbens. A similar pattern was observed following stimulation of mu receptors in the dorsal striatum; however, the extent of activation was much smaller in magnitude. These results suggest that the role of mu receptors within the striatum in palatable feeding primarily involves ventral and lateral regions. Moreover, the pattern of activation in hypothalamic, midbrain and gustatory-visceral relay areas suggests that striatal mu receptors may participate in integrating motivational, metabolic and autonomic aspects of ingestive behavior.


Plasma level of the creatine phosphokinase BB isoenzyme during experimental intestinal ischemia.
Changes in the serum of CPK-BB isoenzyme were investigated in dogs with intestinal ischemia in order to determine their use as an enzymatic diagnostic test for bowel infarction. The study consisted of 12 mongrel dogs. Group I (n = 6) was assigned as a control and was subjected to lumen obstruction of a jejunal segment 50-60 cm in length. Group II (n = 6) had an intestinal infarction created by ligation of the arteries of a jejunal segment 50-60 cm in length. A catheter was placed into the right atrium through the left jugular vein for blood sampling and monitoring. Blood samples were withdrawn every three hours for biochemical assays. CPK-BB measurements were performed by electrophoresis in agarose gel. CPK-BB remained unchanged in Group I during the course of the study (median range 17 to 20 IU) showing no significant difference from normal levels. Significant elevation of CPK-BB occurred three hours after establishing the ischemia in Group II (median 50 IU) as compared to Group I (p less than 0.05). The highest levels were determined to be 96 and 80 IU at the sixth and ninth hour, respectively. From hour 15 until completion of the experiment, no significant difference was detected between Groups I and II. We conclude that CPK-BB elevation in serum signifies its release from the smooth muscles of the bowel due to ischemic cellular damage.


Spontaneous pneumothorax with isolated pulmonary Langerhans cell histiocytosis in an adult case: A common manifestation of rare disease.
Pulmonary Langerhans cell histiocytosis should be evaluated even in adults with no previous medical history and no history of cigarette smoking who have spontaneous pneumothorax and evidence of multiple lung cystic lesions, and other organs should also be checked for multi organ Langerhans cell histiocytosis involvement. A 30-year-old man presented with sudden chest pain and evidence of multiple cystic lesions in both upper and lower lobes of lungs, as well as left-sided pneumothorax in high resolution computed tomography. In lung samples, hematoxylin and eosin- stained sections and IHC for CD1a, S100, and BRAF V600 were positive. The patient was diagnosed with isolated pulmonary Langerhans cell histiocytosis and was treated accordingly.


The bacterial effector Cif interferes with SCF ubiquitin ligase function by inhibiting deneddylation of Cullin1.
Cycle inhibiting factor (Cif) is one of the effectors delivered into epithelial cells by enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli (EHEC) via the type III secretion system (TTSS). Cif family proteins, which inhibit host cell-cycle progression via mechanisms not yet precisely understood, are highly conserved among EPEC, EHEC, Yersinia pseudotuberculosis, Photorhabdus luminescens and Burkholderia pseudomallei. Levels of several proteins relevant to cell-cycle progression are modulated by Cullin-RING ligases (CRLs), which in turn are activated by conjugation and deconjugation of NEDD8 to Cullins. Here we show that Cif interacts with NEDD8 and interferes with SCF (Skp1-Cullin1-F-box protein) complex ubiquitin ligase function. We found that neddylated Cullin family proteins accumulated and ubiquitination of p27 decreased in cells infected with EPEC. Consequently, Cif stabilized SCF substrates such as CyclinD1, Cdt1, and p27, and caused G1 cell-cycle arrest. Using time-lapse-imaging of fluorescent ubiquitination-based cell-cycle indicator (Fucci)-expressing cells, we were able to monitor cell-cycle progression during EPEC infection and confirmed the arrest of infected cells at G1. Our in vitro and in vivo data show that Cif-NEDD8 interaction inhibits deneddylation of Cullins, suppresses CRL activity and induces G1 arrest. We thus conclude that the bacterial effector Cif interferes with neddylation-mediated cell-cycle control.


Inducible nitric oxide synthase and vascular endothelial growth factor are colocalized in the retinas of human subjects with diabetes.
Nitric oxide (NO) mediates vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular hyperpermeability. This study was undertaken to study the cellular distribution of inducible nitric oxide synthase (iNOS) and VEGF in the retinas from human subjects with diabetes mellitus. In addition, glial reactivity and peroxynitrite generation were detected by immunolocalization of glial fibrillary acidic protein (GFAP) and nitrotyrosine, respectively. Eight post-mortem eyes from four consecutive subjects with diabetes mellitus and eight eyes from four subjects without diabetes and without known ocular disease were prospectively collected and examined. We used immunohistochemical techniques and antibodies directed against iNOS, VEGF, GFAP, and nitrotyrosine. In retinas from all subjects without diabetes, weak GFAP immunoreactivity was confined to nerve fibre and ganglion cell layers. There was no immunoreactivity for iNOS, nitrotyrosine, and VEGF. All diabetic retinas showed GFAP induction in Müller cells and GFAP upregulation in nerve fibre and ganglion cell layers. All diabetic retinas showed cytoplasmic immunoreactivity for iNOS, and VEGF in ganglion cells, cells in the inner nuclear layer, and glial cells. In serial sections, ganglion cells and cells in the inner nuclear layer expressing VEGF were localized in the same area of iNOS-expressing ganglion cells and cells in the inner nuclear layer. Six retinas from three subjects with diabetes showed immunoreactivity for nitrotyrosine in vascular endothelial cells in inner retinal layer. iNOS and VEGF are colocalized in diabetic retinas. Increased GFAP immunoreactivity is a pathological event in the retina during diabetes.


Structural basis for the anticoagulant activity of heparin. 2. Relationship of anticoagulant activity to the thermodynamics and fluorescence fading kinetics of acridine orange-heparin complexes.
Complexing heparin or dermatan sulfate with the fluorescent probe acridine orange provides a means of studying electrostatic as well as static and dynamic conformational aspects of these glycosaminoglycans via the thermodynamic and photochemical (fluorescence fading) properties of these complexes. The cooperative binding constants (Kq), fluorescence fading rate parameters (r''), and anticoagulant activities of heparins fractionated according to anionic density all showed qualitatively the same dependence upon anionic density. When Kq and r'' were plotted against anticoagulant activity, empirical relationships were observed. Interestingly, the corresponding values for unfractionated dermatan sulfate fell on the lines defined by the heparin fractions. Temperature-dependence, studies demonstrated that differences in fading rate observed for heparins of different anionic densities are entropic in origin and reflect differences in the ability to assume a special configuration. Differences in activation entropy for fluorescence fading can be empirically correlated with anticoagulant activity. The latter correlation suggests a physical similarity in the roles played by anionic density in both fluorescence fading and anticoagulant activity.


In vivo biopanning: A methodological approach to identifying novel targeting ligands for delivery of biological agents to the vasculature.
In order for gene delivery to be clinically acceptable, a number of crucial developments need to be made to existing vectors. Significant advances have been made in the identification of novel platform vectors that possess modified tropism to the native vector, directing infectivity away from nontarget tissues such as the liver. In order to fully optimize these detargeted platform vectors, they need to be retargeted toward a chosen, defined site, which will be defined according to the disease studied. The successful transition of targeting peptides identified using in vitro screening protocols to an in vivo disease model may be compromized by the complexity of delivery into an intact biological system. To this end, peptides identified using in vivo biopanning may prove to be of greater clinical significance given that they were identified in the disease model of choice and so should translate more successfully to the intact preclinical model. Exploitation of the heterogeneity of the vascular endothelium using such an approach will go a long way toward improving the efficiency and achieving site-specific gene expression, with important clinical implications for the systemic application of gene delivery.


Neuroendocrine Tumour of the Middle Ear: A Case Report.
Neuroendocrine tumour of the middle ear is a rare entity. Here we present a case of a 50 year old male who presented with a polyp in the left external auditory canal. Surgical excision followed by immunohistochemistry confirmed it to be a neuroendocrine tumour.


Clinical significance of tumor volume in endometrial cancer: a Japan-Korea cooperative study.
The aim of this study was to elucidate the significance of tumor volume as a risk factor for predicting lymph node metastasis. We applied the tumor volume index to the data that were collected for 327 Korean patients with endometrial cancer who underwent preoperative assessment including magnetic resonance imaging (MRI) and subsequent surgery including systematic lymphadenectomy. The volume index, which we previously reported in the literature, was defined as the product of maximum longitudinal diameter along the uterine axis, maximum anteroposterior diameter in a sagittal section image, and maximum horizontal diameter in a horizontal section image according to MRI data, from 425 Japanese women with endometrial cancer. Relationships between lymph node metastasis and results of preoperative examinations including volume index were analyzed by logistic regression analysis. The prevalence of affected lymph nodes was 14.2%. Multivariate analysis showed that high-grade histology assessed by endometrial biopsy [odds ratio (OR); 2.9, 95% confidence interval (CI): 1.4-6.4], volume index (OR; 2.4, 95% CI: 1.1-5.3), node enlargement assessed by MRI (OR; 4.2, 95% CI: 1.4-13.2), and high serum cancer antigen (CA)125 level (OR; 3.6, 95% CI: 1.6-8.1) were significantly and independently related to lymph node metastasis. When volume index was excluded from the analysis, myoinvasion assessed by MRI was an independent risk factor for lymph node metastasis as well as high-grade histology, node enlargement, and high serum CA125 level. Volume index is compatible with myometrial invasion as a factor for predicting lymph node metastasis in endometrial cancer.


Characterization of the Proteins Associated with Caulobacter crescentus Bacteriophage CbK Particles.
Bacteriophage genomes contain an abundance of genes that code for hypothetical proteins with either a conserved domain or no predicted function. The Caulobacter phage CbK has an unusual shape, designated morphotype B3 that consists of an elongated cylindrical head and a long flexible tail. To identify CbK proteins associated with the phage particle, intact phage particles were subjected to SDS-PAGE, and the resulting protein bands were digested with trypsin and analyzed using MALDI mass spectroscopy to provide peptide molecular weights. These peptide molecular weights were then compared with the peptides that would be generated from the predicted amino acid sequences that are coded by the CbK genome, and the comparison of the actual and predicted peptide masses resulted in the identification of single genes that could code for the set of peptides derived from each of the 20 phage proteins. We also found that CsCl density gradient centrifugation resulted in the separation of empty phage heads, phage heads containing material organized in a spiral, isolated phage tails, and other particulate material from the intact phage particles. This additional material proved to be a good source of additional phage proteins, and preliminary results suggest that it may include a CbK DNA replication complex.


The effect of tin prefiltration on extremity cone-beam CT imaging with a twin robotic X-ray system.
While tin prefiltration is established in various CT applications, its value in extremity cone-beam CT relative to optimized spectra has not been thoroughly assessed thus far. This study aims to investigate the effect of tin filters in extremity cone-beam CT with a twin-robotic X-ray system. Wrist, elbow and ankle joints of two cadaveric specimens were examined in a laboratory setup with different combinations of prefiltration (copper, tin), tube voltage and current-time product. Image quality was assessed subjectively by five radiologists with Fleiss' kappa being computed to measure interrater agreement. To provide a semiquantitative criterion for image quality, contrast-to-noise ratios (CNR) were compared for standardized regions of interest. Volume CT dose indices were calculated for a 16 cm polymethylmethacrylate phantom. Radiation dose ranged from 17.4 mGy in the clinical standard protocol without tin filter to as low as 0.7 mGy with tin prefiltration. Image quality ratings and CNR for tin-filtered scans with 100 kV were lower than for 80 kV studies with copper prefiltration despite higher dose (11.2 and 5.6 vs. 4.5 mGy; p < 0.001). No difference was ascertained between 100 kV scans with tin filtration and 60 kV copper-filtered scans with 75% dose reduction (subjective: p = 0.101; CNR: p = 0.706). Fleiss' kappa of 0.597 (95% confidence interval 0.567-0.626; p < 0.001) indicated moderate interrater agreement. Considerable dose reduction is feasible with tin prefiltration, however, the twin-robotic X-ray system's low-dose potential for extremity 3D imaging is maximized with a dedicated low-kilovolt scan protocol in situations without extensive beam-hardening artifacts. Low-kilovolt imaging with copper prefiltration provides a superior trade-off between dose reduction and image quality compared to tin-filtered cone-beam CT scan protocols with higher tube voltage.


EEG μ rhythm in virtual reality reveals that motor coding of visual objects in peripersonal space is task dependent.
Previous fMRI studies have shown that the visual perception of manipulable objects spontaneously involves the sensorimotor system, especially when the objects are located in peripersonal space. However, it has also been suggested that the motor coding of manipulable objects perceived in peripersonal space depends on an anticipation to interact with them. The present study aims at clarifying this issue by analyzing healthy adults' EEG activity on the centro-parietal region while perceptually judging intrinsic (prototypical or distorted shape) or extrinsic (reachable or not reachable location) properties of visual objects. In both the object identification and reachability judgment tasks, time-frequency decomposition of EEG signals was performed across the first 1000 ms following object presentation for trials on which no post-stimulus response was required (90% of the trials). Event-Related-(De)Synchronization (ERD/S) of μ rhythm was computed using the 150 ms pre-stimulus period as baseline. In the reachability judgment task, EEG analysis showed a desynchronization of μ rhythm starting 300 ms after object presentation, but only when the objects were presented with a prototypical shape in peripersonal space. For those objects, desynchronization of μ rhythm diminished progressively from peripersonal to extrapersonal space. By contrast, no such gradient was observed in the object identification task. On the whole, these data indicate that motor coding of visual objects expressed in the μ rhythm depends on an object's shape and location in space, but also on the goal of the perceptual task.


Mycotoxins in cereal grain (part 15). Distribution of deoxynivalenol in naturally contaminated wheat kernels.
The analysis of deoxynivalenol (DON) in naturally infected wheat samples, after having been separated into four fractions through laboratory sieves, showed very low levels of DON in the fraction of largest kernels >2.8 mm (0 up to 1 mg/kg). The highest concentration of DON was found in fractions 2.2 to 2.5 mm and <2.2mm with up to 14mg/kg and 15mg/kg DON, respectively. In two samples (fractions <2.2mm) nivalenol was detected in concentrations up to 1,4mg/kg.


Isotope dilution ICP-MS with laser-assisted sample introduction for direct determination of sulfur in petroleum products.
Inductively coupled plasma isotope dilution mass spectrometry (ICP-IDMS) with direct laser-assisted introduction of isotope-diluted samples into the plasma, using a laser ablation system with high ablation rates, was developed for accurate sulfur determinations in different petroleum products such as 'sulfur-free' premium gasoline, diesel fuel, and heating oil. Two certified gas oil reference materials were analyzed for method validation. Two different 34S-enriched spike compounds, namely, elementary sulfur dissolved in xylene and dibenzothiophene in hexane, were synthesized and tested for their usefulness in this isotope dilution technique. The isotope-diluted sample was adsorbed on a filter-paper-like material, which was fixed in a special holder for irradiation by the laser beam. Under these conditions no time-dependent spike/analyte fractionation was only observed for the dibenzothiophene spike during the laser ablation process, which means that the measured 34S/32S isotope ratio of the isotope-diluted sample remained constant-a necessary precondition for accurate results with the isotope dilution technique. A comparison of LA-ICP-IDMS results with the certified values of the gas oil reference materials and with results obtained from ICP-IDMS analyses with wet sample digestion demonstrated the accuracy of the new LA-ICP-IDMS method in the concentration range of 9.2 microg g(-1) ('sulfur-free' premium gasoline) to 10.4 mg g(-1) (gas oil reference material BCR 107). The detection limit for sulfur by LA-ICP-IDMS is 0.04 microg g(-1) and the analysis time is only about 10 min, which therefore also qualifies this method for accurate determinations of low sulfur contents in petroleum products on a routine level.


Short-term condylar and glenoid fossa changes in infants with Pierre Robin sequence undergoing mandibular distraction osteogenesis.
The purpose was to evaluate short-term changes in condylar and glenoid fossa morphology in infants with Pierre Robin sequence (PRS) undergoing early (age <4 months) mandibular distraction osteogenesis (MDO) for the management of severe airway obstruction. Computed tomography data from infants with PRS who had MDO were compared to those of age-matched control infants without facial skeletal dysmorphology. Surface/volume, linear, and angular measurements of the condyle and glenoid fossa were obtained and compared between infants with PRS and controls. Eleven infants with PRS met the inclusion criteria. There were five female and six male subjects with a mean age at the time of MDO of 41±32 days. Prior to MDO, PRS mandibles had a smaller condylar articulating surface area and volume than age-matched control mandibles, with a more laterally positioned condylar axis (P≤0.05). Following MDO, there were significant increases in condylar articulating surface area and volume, approaching those of normal controls, with further lateral translation of the condylar axis (P≤0.05). Condyle and glenoid fossa morphology is largely normalized following early MDO in infants with PRS. The condylar axis translates laterally as a result of MDO; this change is not observed with mandibular growth in infants without PRS.


Ecotoxicological impact assessment of some heavy metals and their distribution in some fractions of mangrove sediments from Red Sea, Egypt.
The total and fraction concentrations of heavy metals (Mn, Cu, Ni, Pb, Co, and Cd) were analyzed in some sediment fractions (Φ2, Φ3, Φ4, Φ5) of selected mangrove ecosystems collected from the Egyptian Red Sea shoreline. The results revealed that manganese had the highest mean value (133 ± 97 mg/kg) followed by copper (49.9 ± 46.0 mg/kg), nickel (28.1 ± 11.8 mg/kg), lead (19 ± 13 mg/kg), cobalt (6.7 ± 4.0 mg/kg), and cadmium (3.327 ± 1.280 mg/kg). The concentrations of heavy metals in the different sediment fractions showed that there was a preferential accumulation of Cu, Co, Mn, and to a lesser degree Cd in the silt and clay fractions rather than in the sand-sized. The sediment quality was performed by using some sediment quality guidelines. Additionally, the contamination and the risk assessment of these heavy metals were achieved by different methods including, potential ecological risk index, contamination factor, pollution load index, and geoaccumulation index. According to the Sediment Quality Guidelines comparisons, the concentrations of Mn and Pb were low and showed no possibility of detrimental effects on the local environment. The levels of Cu and Ni were high, however, could not be considered to present serious threat to the mangrove ecosystem. The data showed that the mangrove ecosystems were affected by the Cd risk.


Clavicle morphometry revisited: a 3-dimensional study with relevance to operative fixation.
The advocacy for operative fixation of midshaft clavicle fractures has prompted a reemergence of interest in clavicle anatomy. Three-dimensional (3D) anatomical studies provide more information than 2-dimensional studies, but are currently rare. Twenty-five skeletonized clavicles were digitized using a laser scanner. Three-dimensional computer software was used to analyze the data. Clavicles were divided into medial, middle, and lateral segments based on the medial and lateral apices of curvature and their lengths and midpoint cortical diameter measured. The angles of medial and lateral curvatures were measured in standardized axial and coronal planes. The medial and lateral curvatures were fitted with circles and the radii of curvature measured. Correlations between the intrinsic dimensions of the clavicle were assessed. The mean length was 136.7 mm. The medial, middle, and lateral segments had mean lengths of 48, 56, and 32.7 mm, respectively. In the axial plane, the mean medial and lateral angles were 149.5° and 145.8°, respectively. In the coronal plane, the mean medial and lateral angles were 178.2° and 174.2°, respectively. The mean midpoint cortical diameter was 10.9 mm. The mean medial and lateral radii of curvature were 66.4 and 33.5 mm, respectively. The length and cortical diameter and length and medial radius of curvature were found to positively correlate, R(2) = .355 and .184, respectively. Using standardized measurements, we were able to accurately characterize the dimensions of the clavicle. We found that the length of the clavicle correlates with the midpoint cortical diameter and with the radius of medial curvature.


Isolated pneumaturia.
Sixteen patients with pneumaturia as their only urologic complaint were evaluated during a 38-year period. In three patients, a vesico-enteric fistula was documented. Five patients had an otherwise asymptomatic urinary tract infection. In eight patients, no pathologic process could be identified. These eight patients were women and had a benign course on follow-up. Urine culture gave positive results in all cases with a documented pathologic condition but gave negative results in all cases in which no explanation for pneumaturia could be found. Because of the difficulty in diagnosing a vesico-enteric fistula, all patients with isolated pneumaturia should have a thorough medical and urologic evaluation.


Efferent projections of the cat oculomotor reticular omnipause neuron region: an autoradiographic study.
Omnipause neurons (OPNs) are midline pontine neurons that are thought to be instrumental in the generation of saccadic eye movements. Inhibition of the tonically active OPNs is postulated to disinhibit the burst neurons that cause the saccadic discharge in motoneurons, leading to a saccade. To test whether the anatomical connections of OPNs are consistent with this scheme, we studied the efferent projections of the OPN region by using the technique of anterograde transport of tritiated amino acids. Injections into the OPN region yield a distinct pattern of labeled tracts and terminal fields that is different from the patterns following control injections in the surrounding reticular formation. Caudally, there are terminal fields over the paramedian reticular formation, the caudal part of the medial accessory nucleus of the inferior olivary complex, the nucleus prepositus hypoglossi, and the nucleus reticularis paragigantocellularis dorsalis caudal and ventromedial to the abducens nuclei. Rostrally, terminal label is distributed over parts of the nuclei reticularis pontis caudalis and oralis, the nucleus raphe pontis, the nucleus reticularis tegmenti pontis, the mesencephalic reticular nucleus, the central gray, and the nucleus of the H-field. Thus, there are direct projections from the OPN region to all areas known to contain burst neurons. In addition, OPNs also apparently have indirect access to the spinal cord and cerebellum. Many of the latter connections parallel the efferent projections of the superior colliculus.


Lower level of IL-28A as a predictive index of the artificial liver support system in effective treatment of patients with HBV-ACLF.
HBV-related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure with high mortality. Artificial liver support system (ALSS) is an important mean to reduce the mortality of HBV-ACLF but lacking index to assess its effectiveness. The cytokines are closely related to the prognosis of HBV-ACLF patients with ALSS treatment, however, which is not fully understood. One hundred forty-two patients with HBV-ACLF and 25 healthy donors were enrolled. The cytokine profile of peripheral blood was determined in the patients before and after ALSS treatment, and their relationship with effectiveness of ALSS treatment in HBV-ACLF was analyzed. Serum IL-28A levels were markedly lower in ALSS-effective patients than those in non-effective patients pre-ALSS treatment. Similarly, serum IL-6 was significantly lower in ALSS-effective patients. Furthermore, for patients with effective treatment, serum IL-28A levels were positively related with IL-6 levels post-ALSS (r = 0.2413, p = 0.0383). The ROC curve analysis showed that serum levels of IL-28A (AUC = 0.6959 when alone or 0.8795 when combined with total bilirubin, platelet count and INR, both p < 0.0001) and IL-6 (AUC = 0.6704, p = 0.0005) were useful indices for separating effective from non-effective ALSS treatment of HBV-ACLF patients. Multivariate logistic regression analysis demonstrated that lower level of IL-28A was independently associated with higher effective rate of ALSS treatments. Lower level of IL-28A is a predictive biomarker for ALSS in effective treatment of HBV-ACLF patients and IL-28A may be potential target for the treatment of HBV-ACLF.


Gender differences in alcohol-induced neurotoxicity and brain damage.
Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse.


Strategies for cloning unknown cellular flanking DNA sequences from foreign integrants.
Many virus and transposon DNAs can integrate into the host genome. In this review, techniques, including inverse polymerase chain reaction (IPCR), novel Alu-PCR and vectorette- or splinkerette-PCR are introduced as possible strategies for cloning flanking DNA regions of the integrants. Targeted gene-walking PCR, restriction-site PCR, capture PCR, and panhandle PCR and boomerang DNA amplification are also described. The principles, advantages and limitations of each approach are discussed.


Acebutolol. A review of its pharmacological properties and therapeutic efficacy in hypertension, angina pectoris and arrhythmia.
Acebutolol is a cardioselective beta-adrenoceptor blocking drug possessing both partial agonist (intrinsic sympathomimetic) and membrane stabilising activity. In hypertension, it can be administered once or twice daily with equal effectiveness, and has been as effective at lowering blood pressure as propranolol, diuretics, and other beta-blocking drugs (metoprolol, labetalol and atenolol) and more effective than methyldopa. Acebutolol has a significantly smaller effect on resting heart rate than propranolol, metoprolol and atenolol, although direct comparisons with drugs with intrinsic sympathomimetic activity have yet to be undertaken. In both angina and arrhythmia, when administered twice daily it has been as effective as standard therapeutic agents. The side effect profile of acebutolol appears to be comparable to that of other cardioselective beta-blockers. Its relative cardio-selectivity, partial agonist and membrane stabilising activity, hydrophilicity, and considerable extrarenal excretion may offer advantages over some beta-blocking drugs in specific patients. Choosing a beta-blocking agent, however, should be made with a knowledge of pharmacodynamic and pharmacokinetic properties of the various agents and careful consideration of how such properties may be of benefit to an individual patient.


Temporal/spatial expression of retinoid binding proteins and RAR isoforms in the postnatal lung.
Endogenous retinoids have been implicated in alveologenesis in both the rat and the mouse, and exogenous retinoic acid (RA) can reverse or partially reverse experimental emphysema in adult rat and mouse models by an unknown mechanism. In this study, we examine the cellular and molecular biology of retinoid signaling during alveologenesis in the mouse. We describe the temporal and spatial expression of the retinoid binding proteins CRBP-I, CRBP-II, and CRABP-I using RT-PCR and immunohistochemistry. We identify the retinoic acid receptor isoforms RAR-alpha 1, RAR-beta 2, RAR-beta 4, and RAR-gamma 2 and describe their temporal and spatial expression using RT-PCR and in situ hybridization. We demonstrate that both retinoid binding proteins and RAR isoforms are temporally regulated and found within the alveolar septal regions during alveologenesis. These data support a role of dynamic endogenous RA signaling during alveolar formation.


Tackling the 'Planned Lack of Care': Could a Right to Development Treaty Promote Universal Social Protection Systems?
The opportunity offered by the adoption of a Treaty on the Right to Development could relaunch aspirations of sovereignty, self-determination and cooperative solidarity, breaking with the structural inequalities among and within nations. The aim of this article is to mobilize political actors in favour of the Treaty as a stepping-stone to achieve universal social protection systems.


Prognostic potential of detection of WT1 mRNA level in peripheral blood in adult acute myeloid leukemia.
We retrospectively analyzed the potential of Wilms' tumor gene 1 (WT1) mRNA levels in peripheral blood for predicting the prognosis of 50 patients with AML. After achieving complete remission (CR), 34 patients (69.4%) were determined to be positive and 15 (30.6%) were negative for WT1. The relapse rate of the positive and negative patients was 73.5% and 40.0% (p = 0.02), respectively. After consolidation therapy, only 15 patients (32.6%) were positive and 31 (67.4%) were negative for WT1. Although the relapse rate of the positive and negative patients was 80.0% and 54.8% (p = 0.10), respectively, the rate of relapse within 1 year was 73.3% in positive patients and only 33.3% in negative patients (p = 0.01), respectively. The disease-free survival (DFS) rate at 3 years was 20.0% for positive patients and 50.0% for negative patients (p = 0.01). The overall survival (OS) rate at 3 years was 42.8% in positive patients and 69.8% in negative patients (p = 0.04), respectively. WT1 mRNA levels in the peripheral blood can predict relapse after CR, and its levels after consolidation therapy are closely correlated with DFS, OS, and early relapse.


Association of Maternal Use of Triptans During Pregnancy With Risk of Attention-Deficit/Hyperactivity Disorder in Offspring.
Triptans are commonly used in the treatment of migraine. Prenatal exposure to triptans may be associated with adverse fetal neurodevelopment; however, there is limited information about the long-term safety of triptan use during pregnancy. To examine the association between maternal use of triptans during pregnancy and diagnosis and symptoms of attention-deficit/hyperactivity disorder (ADHD) among offspring. This study used data from the Norwegian Mother, Father and Child Cohort Study (recruitment 1999-2008), linked to national health registries. Live-born singleton children born to women with migraine before or during pregnancy were included. Two analytic samples were defined: one to assess ADHD diagnosis and one to assess ADHD symptoms. Data were analyzed from May 1 to November 30, 2021. Maternal self-report of triptan use during pregnancy. Exposed children were compared with 2 groups of unexposed children whose mothers reported migraine (1) during pregnancy and (2) before pregnancy only. An ADHD diagnosis was defined as diagnosis of hyperkinetic disorder or receipt of dispensed ADHD medication. Symptoms of ADHD at 5 years were measured by the Conners' Parent Rating Scale, where a higher score indicates more symptoms of ADHD. Cox proportional hazards regression models and generalized linear models with inverse probability weights were used to estimate weighted hazard ratios (HRs) and standardized mean differences, respectively, with 95% CIs. The ADHD diagnosis sample comprised 10 167 children (mean [SD] maternal age, 30.2 [4.6] years; 5231 boys [51.5%]), and the ADHD symptoms sample comprised 4367 children (mean [SD] maternal age, 30.6 [4.4] years; 2191 boys [50.2%]). Children were followed up for a mean (SD) of 10.6 (2.2) years. Children with prenatal triptan exposure had no increased risk of ADHD diagnosis compared with unexposed children whose mothers had migraine during pregnancy (weighted HR, 1.16; 95% CI, 0.78-1.74) and compared with unexposed children whose mothers had migraine only before pregnancy (weighted HR, 1.28; 95% CI, 0.84-1.94). There were no differences in ADHD symptom scores between exposed and unexposed children. The findings of this study suggest that there is no increased risk of ADHD among offspring associated with prenatal exposure to triptans.


The lncRNA THOR interacts with and stabilizes hnRNPD to promote cell proliferation and metastasis in breast cancer.
Emerging evidence shows that the lncRNA THOR is deeply involved in the development of various cancers. However, the effects and underlying molecular mechanisms of THOR in breast cancer (BRCA) initiation and progression have not been fully elucidated. Here we show that THOR is critical for BRCA tumorigenesis by interacting with hnRNPD to regulate downstream signaling pathways. THOR expression was significantly higher in BRCA tissues than in normal tissues, and THOR upregulation was associated with a poor prognosis in BRCA patients. Functionally, THOR knockdown impaired cell proliferation, migration and invasion in BRCA cells in vitro and inhibited tumorigenesis and metastasis in a tumor xenograft model and THOR-deficient MMTV-PyMT model in vivo. Mechanistically, THOR bound to the hnRNPD protein and increased hnRNPD protein levels by maintaining hnRNPD protein stability through inhibition of the proteasome-dependent degradation pathway. The increased hnRNPD protein levels led to stabilization of its target mRNAs, including pyruvate dehydrogenase kinase 1 (PDK1), further activating downstream PI3K-AKT and MAPK signaling pathways to regulate BRCA cell proliferation and metastasis. Together, our findings indicate that THOR is a promising prognostic predictor for BRCA patients and that the THOR-hnRNPD-PDK1-MAPK/PI3K-AKT axis might be a potential therapeutic target for BRCA treatment.


Emergence of antibiotic-resistant Mycoplasma genitalium as the cause of non-gonococcal urethritis in male patients at a sexually transmitted infection clinic.
Mycoplasma genitalium is the cause of an emerging sexually transmitted infection (STI) with high propensity for development of antimicrobial resistance. In a prevalence study conducted at the public STI service in Hong Kong, the first void urine samples of 38 (8%) of 493 male patients with non-gonococcal urethritis (NGU) tested positive for M. genitalium using reverse transcription polymerase chain reaction. Patients with M. genitalium infection were younger [31 vs 33 years, odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.996; P=0.03], more likely to present with urethral discharge (12% vs 6%, OR 2.16, 95% CI 1.10-4.23; P=0.02) and had symptom duration >2 weeks (14% vs 6%, OR 2.34, 95% CI 1.10-4.97; P=0.03) compared with patients without M. genitalium infection. The prevalence of M. genitalium infection was lower in patients co-infected with Chlamydia trachomatis compared with patients with isolated infection (4% vs 10%, OR 0.38, 95% CI 0.17-0.84; P=0.02). The prevalence of M. genitalium infection was not higher in men who have sex with men. Antimicrobial-resistance-conferring mutations were present in 24 (63%) patients with M. genitalium - 23S rRNA 18 (47%) and parC 19 (53%). Similar to neighbouring countries in the Asia Pacific region, concurrent resistance mutations against both macrolides and fluoroquinolones were demonstrated in 14 (37%) patients. Histories of azithromycin and moxifloxacin use were significantly associated with a diagnosis of M. genitalium infection. Characteristically, NGU in Hong Kong featured the co-existence of mono-resistance against macrolides or fluoroquinolones, and the presence of dual class resistance. The geographic variability of antimicrobial resistance against M. genitalium is attributed not just to the different transmission networks formed in separate population groups, but the antimicrobial prescriptions for the treatment of urethritis in the community.


Level of thyroid-stimulating hormone (TSH) in patients with acute schizophrenia, unipolar depression or bipolar disorder.
The aim of this study is to investigate differences in thyroid-stimulating hormone (TSH) level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Serum level of TSH was measured in 1,685 Caucasian patients (1,064 women, 63.1%; mean age 46.4). Mean serum TSH concentration was: schizophrenia (n = 769) 1.71 μIU/mL, unipolar depression (n = 651) 1.63 μIU/mL, bipolar disorder (n = 264) 1.86 μIU/mL, bipolar depression (n = 203) 2.00 μIU/mL, bipolar mania (n = 61) 1.38 μIU/mL (H = 11.58, p = 0.009). Depending on the normal range used, the overall rate of being above or below the normal range was 7.9-22.3% for schizophrenia, 13.9-26.0% for unipolar depression, 10.8-27.6% for bipolar disorder, 12.2-28.5% for bipolar depression, and 11.4-24.5% for bipolar mania. We have also found differences in TSH levels between the age groups (≤20, >20 years and ≤40, >40 years and ≤60 years and >60 years). TSH level was negatively correlated with age (r = -0.23, p < 0.001). Weak correlations with age have been found in the schizophrenia (r = -0.21, p < 0.001), unipolar depression (r = -0.23, p < 0.001), bipolar depression (r = -0.25, p = 0.002) and bipolar disorder (r = -0.21, p = 0.005) groups. Our results confirm that there may be a higher prevalence of thyroid dysfunctions in patients with mood disorders (both unipolar and bipolar) and that these two diagnostic groups differ in terms of direction and frequency of thyroid dysfunctions.


Evaluation of oxidative stress markers and intra-extracellular antioxidant activities in patients with endometriosis.
The aim of the study is to evaluate alterations in intracellular and extracellular antioxidant enzymes activities and serum oxidative stress markers in patients with endometriosis. The current prospective study consisted of 31 female patients with endometriosis and 27 healthy controls. Serum total thiol, native thiol, disulphide, catalase, myeloperoxidase, and ceruloplasmin concentrations were measured. Laboratory and clinical data of all participants were recorded to compare the differences between the study and the control groups. Serum native thiol and total thiol levels in the study group were significantly lower than those in the control group [(p=0.009, p=0.03, respectively)]. Serum catalase levels are significantly higher in patients with endometriosis comparing to the control group (p=0.009). The finding that significant differences in serum total thiol, native thiol, and catalase levels observed in endometriotic patients supports that oxidative stress carries weigh in the pathophysiological aspects of endometriosis. Also significantly low levels of extracellular antioxidants and significantly high levels of intracellular antioxidants in endometriotic patients may arise from differences of free radicals in endometriosis and the activity levels of endometriosis. These non-invasive serum markers might give us an opportunity to monitor the disease's progress during the treatment.


Retrospective Analysis of Sugammadex Use in Adolescent Females on Progestin-Containing Contraceptives.
Sugammadex, a novel neuromuscular blockade reversal agent, functions as a steroid binder postulated to decrease hormone exposure used within progestin-containing contraceptive medications. Thus, alternative non-medication contraceptive methods are recommended to prevent unplanned pregnancies. The study aims were to evaluate sugammadex use in adolescent females prescribed a progestin-containing contraceptive and positive pregnancy screening frequency. We hypothesized that sugammadex use is infrequent in this population and no pregnancy screens would be positive. This is a retrospective observational cohort study utilizing the TriNetX electronic health record database of female subjects aged 12-21 years reported to be prescribed sugammadex. The data collected were analyzed for demographic characteristics, International Classification of Diseases 9th and 10th edition diagnostics, medication, procedural codes, progestin-containing medication timing, and timing of pregnancy screening. We included 18,686 subjects (contraceptive group, 2017 [10.8%], and no contraceptive group, 16,669 [89.2%]). Both groups had similar frequencies of pregnancy screening (contraceptive group, 54 [2.7%], vs no contraceptive group, 366 [2.2%]). Of the contraceptive group, 1 (0.05%) subject, 17 years of age, was confirmed to have a positive pregnancy screen 35 days after surgery. We found that sugammadex may be administered to adolescent females prescribed progestin-containing contraceptives, but positive pregnancy screens are rare. Effective counseling, use of nonhormonal contraceptives 7 days after sugammadex administration, and the theoretical reproductive risks of this agent may have contributed to these findings. Continued counseling after sugammadex use in the adolescent population is recommended to avoid the occurrence of unplanned pregnancies.


Investigating the Role of Vacancies on the Thermoelectric Properties of EuCuSb-Eu2 ZnSb2 Alloys.
AMX compounds with the ZrBeSi structure tolerate a vacancy concentration of up to 50 % on the M-site in the planar MX-layers. Here, we investigate the impact of vacancies on the thermal and electronic properties across the full EuCu1-x Zn0.5x Sb solid solution. The transition from a fully-occupied honeycomb layer (EuCuSb) to one with a quarter of the atoms missing (EuZn0.5 Sb) leads to non-linear bond expansion in the honeycomb layer, increasing atomic displacement parameters on the M and Sb-sites, and significant lattice softening. This, combined with a rapid increase in point defect scattering, causes the lattice thermal conductivity to decrease from 3 to 0.5 W mK-1 at 300 K. The effect of vacancies on the electronic properties is more nuanced; we see a small increase in effective mass, large increase in band gap, and decrease in carrier concentration. Ultimately, the maximum zT increases from 0.09 to 0.7 as we go from EuCuSb to EuZn0.5 Sb.


Sentinel lymph node biopsy is precise after primary systemic therapy in stage II-III breast cancer patients.
Sentinel lymph node biopsy (SLNB) without axillary lymph node dissection (ALND) in SLN negative patients is a standard of care for most breast cancer patients. SLNB for axillary staging after primary systemic therapy (PST) is still under discussion because of possibly reduced accuracy, while data are lacking. The purpose of this study was to evaluate the accuracy of SLNB after PST. A total of 185 breast cancer patients were treated with PST; 160 patients received preoperative chemotherapy, and 25 patients received preoperative endocrine therapy. Thus, 143 of 160 patients with preoperative chemotherapy and 22 of 25 patients with preoperative endocrine therapy were eligible for evaluation. The combination of blue dye and radioactive tracer was used for identification of SLNs. All patients received SLNB and axillary lymph node dissection (ALND). Pathologic assessment of SLNs was performed and compared to non-SLN status. Pathologic complete response rates and breast conserving therapy rates were 15.4 and 78.3% in the preoperative chemotherapy group and 0 and 77.3% in the preoperative endocrine therapy group, respectively. Identification rate, sensitivity, overall accuracy, and false-negative rate were 81.1% (116 of 143), 91.7% (55 of 60), 95.7% (111 of 116), and 8.3% (5 of 60) in the preoperative chemotherapy group and 77.3% (17 of 22), 90.0% (9 of 10), 94.1% (16 of 17), and 10.0% (1 of 10) in the preoperative endocrine therapy group, respectively. SLNB after primary systemic therapy is accurate, and the results are comparable to those of primary SLNB. SLNB after PST could spare ALND in up to 40% of patients with primary positive axillary lymph nodes and should be considered as a standard for axillary staging in those patients.


Bone morphogenetic proteins in fracture repair.
Bone fractures represent a significant medical morbidity among aged population with osteoporosis. Bone morphogenetic proteins (BMPs) are suggested to have therapeutic potential to enhance fracture healing in such patients. Though BMP-mediated fracture healing has been well-documented in preclinical models, there has been no clinical study that demonstrated unequivocally that indeed a BMP when presented with an appropriate scaffold could provide basis for robust outcome for delayed or non-union diaphyseal bone fractures. This review presents a comprehensive insight towards the existing knowledge on the role of BMP signaling in bone formation and maintenance. Also therapeutic options based on BMP biology are discussed.A novel osteoinductive autologous bone graft substitute (ABGS) aimed to accelerate bone regeneration was developed and is currently being tested in the clinical setting. It comprises of a biologically compatible autologous carrier made from the patient's peripheral blood (autologous blood coagulum, ABC) and of rhBMP6 as an active ingredient. Such formulation circumvents the use of animal-derived materials, significantly limits inflammatory processes common in commercial bone devices and renders the carrier flexible, malleable, and injectable ensuring the ease of use. The ongoing clinical trials result will provide more detailed insights into the safety, tolerability, pharmacokinetics, and bone healing effects in humans and potentially provide novel and safe therapeutic options for bone repair.


Organization of nucleus rotundus, a tectofugal thalamic nucleus in turtles. III. The tectorotundal projection.
Nucleus rotundus is the primary thalamic recipient of projections from the optic tectum in pond turtles. Although the projection of the retina to the optic tectum is known to be topographically organized, earlier studies suggest that the tectorotundal projection is not topographically organized. Three types of analyses are used in this paper to characterize the organization of the projection of the optic tectum to nucleus rotundus. First, large iontophoretic injections of horseradish peroxidase into the optic tectum anterogradely fill axons with reaction product after the use of a cobalt-enhanced diaminobenzidine procedure. These preparations show that shafts of axons in the tectothalamic tract give rise to thinner, primary collaterals that enter nucleus rotundus from its caudolateral aspect and form sparsely branching arbors within the nucleus. Very thin secondary collaterals branch from these collateral bear terminal collaterals with frequent varicosities. Although the total size of such arbors is unknown, the evidence suggests that each arbor is large in relation to the size of nucleus rotundus. Thus, injection sites restricted to central tectum label axons throughout nucleus rotundus. Second, subtotal lesions of the tectum produce degeneration throughout nucleus rotundus in silver degeneration preparations. Finally, analysis of electron microscopic degeneration material indicates that tectal boutons are distributed along the full lengths of the dendrites of rotundal neurons, but not on their somata. These boutons form asymmetric synaptic junctions and contain round synaptic vesicles. In view of the relatively large size of the dendritic fields of rotundal neurons, these data suggest that the tectorotundal projection is both strongly convergent on individual neurons and strongly divergent from single tectorotundal axons. This type of organization is consistent with physiological evidence that rotundal neurons have receptive fields that cover at least one-half of the contralateral visual field and often include the entire hemifield. It seems unlikely that nucleus rotundus can be involved in neuronal transactions that preserve detailed spatial information, but it may be involved in processing information on other visual parameters such as stimulus velocity or color.


Simplified quantitative determination of total fecal bile acids.
To determine total fecal bile acids, these are extracted with diethyl ether after boiling with a solution of potassium hydroxide in ethanediol. After evaporating the ether and dissolving the residue in methanol, the bile acids are directly determined with 3 alpha-hydroxysteroid dehydrogenase. Values for 9 normals are given.


Transcatheter arterial chemoembolization (TACE) for lymph node metastases in patients with hepatocellular carcinoma.
To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) with regional lymph node metastases. Forty-eight patients with HCC and regional lymph node metastases were enrolled in this study. The patients were allocated into two groups: Group A (28 patients) underwent TACE for both intrahepatic tumors and lymph node metastasis and Group B (20 patients) received TACE for intrahepatic tumors only. The patients were followed-up by contrast enhanced CT scan 6-8 weeks after TACE treatment. In Group A, seven and nine patients achieved complete and partial response for lymph node metastasis, respectively, with 1-year and 2-year overall survival rates of 60.7% and 35.7%, respectively. In contrast, none of the patients in Group B achieved a complete response, whereas four patients achieved a partial response. The 1-year and 2-year survival rates for the patients in Group B were 40% and 0%, respectively. The difference in survival between the two groups was statistically significant (P = 0.001). TACE is an effective treatment to regional lymph node metastasis in HCC without significant side effects and could provide survival benefits to the patients with advanced HCC.


Comparison of a new image-guided system versus partial coherence interferometry, Scheimpflug imaging, and optical low-coherence reflectometry devices: Keratometry and repeatability.
To determine the repeatability of keratometry of the Verion image-guided system and to compare the keratometry (K) values with those of established biometric devices. International Vision Correction Research Centre, Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany. Prospective case series. One randomly chosen eye of volunteers was examined with partial coherence interferometry (PCI) (IOLMaster 500), optical low-coherence reflectometry (OLCR) (Lenstar LS 900), a Scheimpflug device (Pentacam HR), and the new image-guided system by the same examiner. None of the eyes had ocular pathology. Three consecutive measurements were performed with the image-guided system and 1 with the other devices. The flat, steep, and average corneal radii; steep axis; and white-to-white (WTW) distance were analyzed and compared. One hundred twenty-three eyes of 123 volunteers (mean age 37.9 years ± 16.2 [SD]) had valid measurements for all examinations and were available for analysis. The image-guided system measured statistically significant smaller flat, steep, and average corneal radii than the Scheimpflug device, statistically significant larger flat and average corneal radii than the PCI device, and no statistically significant different values than the OLCR device. The measured steep axis did not differ significantly in any comparison. The WTW measurements were significantly higher than those of all other devices. The analysis of repeatability of the image-guided system showed high intraclass correlation coefficients (range 0.919 to 0.997). The new image-guided system had high repeatability for K, steep axis, and WTW measurements. The WTW measurements with the image-guided system were significantly higher than those using the other devices. None of the authors has a financial or proprietary interest in any material or method mentioned.


Autometallographic tracing of mercury in frog liver.
The distribution of mercury in the liver of the frog Rana ridibunda with the autometallographic method was investigated. The mercury specific autometallographic (HgS/SeAMG) technique is a sensitive histochemical approach for tracing mercury in tissues from mercury-exposed organisms. Mercury accumulates in vivo as mercury sulphur/mercury selenium nanocrystals that can be silver-enhanced. Thus, only a fraction of the Hg can be visualized. Six animals were exposed for one day and another group of six animals for 6 days in 1 ppm mercury (as HgCI2 ) dissolved in fresh water. A third group of six animals, served as controls, were sacrificed the day of arrival at the laboratory. First, mercury appears in the blood plasma and erythrocytes. Next, mercury moves to hepatocytes and in the apical part of the cells, that facing bile canaliculi. In a next step, mercury appears in the endothelial and Kupffer cells. It seems likely that, the mercury of hepatocytes moves through bile canaliculi to the gut, most probably bound to glutathione and/or other similar ligands. Most probably, the endothelial and Kupffer cells comprise the first line of defense against metal toxicity.


Medical journey of patients with polycystic ovary syndrome and obesity: a cross-sectional survey of patients and primary care physicians.
Patients with polycystic ovary syndrome (PCOS) report dissatisfaction with the diagnostic process and are more likely to have overweight or obesity. We wanted to understand the role that primary care physicians (PCPs) play in the diagnosis of PCOS and how they contribute to treatment of patients with PCOS and obesity. A cross-sectional online survey was completed by 251 patients with PCOS and obesity (BMI ≥30 kg/m2) and 305 healthcare providers (PCPs, obstetricians/gynecologists, reproductive and general endocrinologists). This paper focuses on the 75 PCPs treating patients with PCOS and obesity. In the most common patient journey, we found that most patients with PCOS and obesity (53%) have initial discussions about PCOS symptoms with PCPs. However, less than one quarter of patients receive a PCOS diagnosis (22%) or initial treatment (24%) for PCOS from a PCP. One quarter of patients also reported receiving a misdiagnosis from a PCP prior to their PCOS diagnosis. Compared to other healthcare providers surveyed, PCPs were the least comfortable making a PCOS diagnosis. Compared to PCPs without an obesity management focus, PCPs with an obesity management focus were more likely to diagnose patients themselves (38% vs 62%) and initiate PCOS treatment themselves (42% vs 57%). According to PCPs, difficulty with obesity management (47%) was the top reason that patients with PCOS and obesity stop seeing them for PCOS management. PCPs are often the initial medical touchpoint for patients with PCOS and obesity. However, PCPs play a smaller role in diagnosis and treatment of PCOS. Increasing education on obesity management may encourage PCPs to diagnose and treat more patients with PCOS and offer strategies to help patients with obesity management.


Application of machine learning to predict the occurrence of arrhythmia after acute myocardial infarction.
Early identification of the occurrence of arrhythmia in patients with acute myocardial infarction plays an essential role in clinical decision-making. The present study attempted to use machine learning (ML) methods to build predictive models of arrhythmia after acute myocardial infarction (AMI). A total of 2084 patients with acute myocardial infarction were enrolled in this study. (All data is available on Github: https://github.com/wangsuhuai/AMI-database1.git) . The primary outcome is whether tachyarrhythmia occurred during admission containing atrial arrhythmia, ventricular arrhythmia, and supraventricular tachycardia. All data is randomly divided into a training set (80%) and an internal testing set (20%). Apply three machine learning algorithms: decision tree, random forest (RF), and artificial neural network (ANN) to learn the training set to build a model, then use the testing set to evaluate the prediction performance, and compare it with the model built by the Global Registry of Acute Coronary Events (GRACE) risk variable set. Three ML models predict the occurrence of tachyarrhythmias after AMI. After variable selection, the artificial neural network (ANN) model has reached the highest accuracy rate, which is better than the model constructed using the Grace variable set. After applying SHapley Additive exPlanations (SHAP) to make the model interpretable, the most important features are abnormal wall motion, lesion location, bundle branch block, age, and heart rate. Among them, RBBB (odds ratio [OR]: 4.21; 95% confidence interval [CI]: 2.42-7.02), ≥ 2 ventricular walls motion abnormal (OR: 3.26; 95% CI: 2.01-4.36) and right coronary artery occlusion (OR: 3.00; 95% CI: 1.98-4.56) are significant factors related to arrhythmia after AMI. We used advanced machine learning methods to build prediction models for tachyarrhythmia after AMI for the first time (especially the ANN model that has the best performance). The current study can supplement the current AMI risk score, provide a reliable evaluation method for the clinic, and broaden the new horizons of ML and clinical research. Trial registration Clinical Trial Registry No.: ChiCTR2100041960.