Lactation exposure to BDE-153 damages learning and memory, disrupts spontaneous behavior and induces hippocampus neuron death in adult rats.
To study the effects of 2,2',4,4',5,5'-hexa-brominated diphenyl ether (BDE-153) exposure during lactation on the learning and memory abilities, spontaneous behavior and brain cells of adult rats and to elicit basic information on PBDE's developmental neurotoxicity. Newborn male rat pups were randomly categorized into the following groups (15 pups per group), according to their weights and litters: a control group, and 1mg/kg, 5mg/kg and 10mg/kg BDE-153 groups. At postnatal day 10 (PND10), the pups in the BDE-153 groups were intraperitoneally injected once with BDE-153 plant oil solutions at 0.1ml/10g body weight, and the controls were injected with plant oil. Throughout the entire experiment, physiological measures were recorded, such as food and water consumption, body weight and clinical symptoms. At 1 month and 2 months after treatment, the learning and memory abilities of the rats were tested by the Morris water maze test, the step-down test, and the step-through test; spontaneous behavior was tested by the open-field test. After all tests were accomplished, rats were weighed and sacrificed, and the brain tissue was immediately isolated and divided into two parts. Sections were fabricated from one part, and changes in the morphology and ultrastructure in CA3 region of hippocampus were observed under an optical microscope and transmission electron microscope, along with the detection of apoptotic cells with the terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method. The tissue of the second part was digested into single-cell suspension liquid, and the cell apoptosis was assayed with flow cytometry and the lactate dehydrogenase (LDH) leakage was detected with spectrophotometry. There was no obvious change in food and water consumption, body weight and the ratio of brain to body weight, or any overt clinical symptoms in the BDE-153-treated rats. Compared to the control group, rats' latency time in the test session (LT2) in the step-down test was significantly increased in the 10mg/kg BDE-153 group at 2 months after treatment (P<0.05), and the BDE-153-treated rats' swimming times and distances in the target quadrant were significantly decreased at 1 month and 2 months after treatment (P<0.05 or P<0.01). These parameters were also significantly increased in the opposite quadrant at 1 month after treatment (P<0.05 or P<0.01). The spontaneous behavior was significantly reduced in the treated groups compared to the controls (P<0.05 or P<0.01). The severity of neurobehavioral dysfunction was dependent on the exposure dose of BDE-153, and worsened with age. Under an optical microscope, the treated rats' neurons in the CA3 region of the hippocampus were observed to be reduced and disarranged, and the cell junctions were loosened and the intercellular spaces were enlarged. Under a transmission electron microscope, the cell nucleus was observed to shrink; the chromatin was condensed and gathered near the nuclear membrane, the Nissl bodies and other organelles in the perikaryon were reduced, and the vacuole was observed to degenerate and even disappear. Moreover, compared to the controls, the cell apoptosis rates were significantly increased in the 5 and 10mg/kg BDE-153 groups (P<0.05), and the LDH activity was significantly increased in the 10mg/kg BDE-153 groups (P<0.01). Lactation exposure to BDE-153 damaged adult rats' learning and memory abilities, disrupted their spontaneous behavior (hypoactivity) and induced hippocampus neuron apoptosis.


Editorial Commentary: Increased Risk of Second Ruptures and Poorer Outcomes After Anterior Cruciate Ligament Injury and Reconstruction in Hypermobile Athletes: A Potential Synergism of Passive Ligamentous and Active Muscular Control of Dynamic Knee Stability Related to Age and Sex?
Graft failure rates were higher and inferior subjective outcomes were observed after anterior cruciate ligament reconstruction in patients with generalized hypermobility. This is a clear and corroborative finding that is highly consilient with other reports of similar studies from the published literature. However, controversy remains regarding other potentially predictive and confounding variables. For example, age, activity level, sex, and dynamic neuromuscular control were not considered in this interesting, important, and potentially impactful study. Dynamic stability of the knee joint is determined by both passive (ligamentous and tendinous) and dynamic (neuromuscular) restraints. Most anterior cruciate ligament (ACL) injuries in high-risk sports such as basketball, football, lacrosse, soccer, and volleyball occur by noncontact mechanisms (landing, deceleration, or lateral pivoting). Noncontact ACL injuries often occur in female athletes by a common 3-part mechanism: dynamic lower extremity valgus loading combined with an extended knee on a single leg. Increased passive laxity of the knee combined with an increased dynamic joint loading profile may lead to the increased ACL injury rates in females. Therefore, the combination of insufficiently taut ligaments and tendons of the lower extremity that may passively destabilize the joint and high knee joint forces and torques that dynamically load an already loose joint may be diagnostic for both primary and secondary ACL injury risk.


Parametric and cadaveric models of lumbar flexion instability and flexion restricting dynamic stabilization system.
Development of a dynamic stabilization system often involves costly and time-consuming design iterations, testing and computational modeling. The aims of this study were (1) develop a simple parametric model of lumbar flexion instability and use this model to identify the appropriate stiffness of a flexion restricting stabilization system (FRSS), and (2) in a cadaveric experiment, validate the predictive value of the parametric model. Literature was surveyed for typical parameters of intact and destabilized spines: stiffness in the high flexibility zone (HFZ) and high stiffness zone, and size of the HFZ. These values were used to construct a bilinear parametric model of flexion kinematics of intact and destabilized lumbar spines. FRSS implantation was modeled by iteratively superimposing constant flexion stiffnesses onto the parametric model. Five cadaveric lumbar spines were tested intact; after L4-L5 destabilization (nucleotomy, midline decompression); and after FRSS implantation. Specimens were loaded in flexion/extension (8 Nm/6 Nm) with 400 N follower load to characterize kinematics for comparison with the parametric model. To accomplish the goal of reducing ROM to intact levels and increasing stiffness to approximately 50 % greater than intact levels, flexion stiffness contributed by the FRSS was determined to be 0.5 Nm/deg using the parametric model. In biomechanical testing, the FRSS restored ROM of the destabilized segment from 146 ± 13 to 105 ± 21 % of intact, and stiffness in the HFZ from 41 ± 7 to 135 ± 38 % of intact. Testing demonstrated excellent predictive value of the parametric model, and that the FRSS attained the desired biomechanical performance developed with the model. A simple parametric model may allow efficient optimization of kinematic design parameters.


Correlation between retroglossal airway size and body mass index in OSA and non-OSA patients using cone beam CT imaging.
Most obstructive sleep apnea (OSA) patients are overweight, and OSA is substantially more common in obese individuals. In morbidly obese patients, at least 70% suffer from OSA. However, the exact mechanism by which obesity causes OSA is unclear. The aim of this study is to evaluate the retroglossal airway configuration quantitatively and to make clear the relationship between Body mass index (BMI) and airway configuration. This retrospective study included 15 OSA patients (male = 11; female = 4) and 14 normal controls (male = 8; female = 6). We studied the airway configuration on an axial slice at the level of the anterior-inferior corner of the second cervical vertebra. Maximum anterior-posterior diameter (AP) and lateral width (LW) of the airway were measured, and the square area (SA) was calculated. The airway cross-section area (AWA) was also measured, and then the AWA/SA ratio was calculated. AP, LW, and AWA were not statistically significantly different between controls and OSA patients. On the other hand, the AWA/SA ratio in OSA patients was 8.8% statistically significantly smaller than in controls after adjusting for sex, age, and BMI. In this sample, there was a negative correlation between age and the AWA/SA ratio but only in the OSA group. The AWA/SA ratio was significantly negatively correlated with OSA status (R = -0.5; p = 0.008) after adjusting for BMI and age. In this present study, we could evaluate the retroglossal airway configuration quantitatively. The AWA/SA ratio was correlated with OSA status after adjusting for BMI and age.


LH pattern and ovarian response in ovsynch-synchronized superovulated goats induced to ovulate with GnRH or hCG.
The intention of the present investigation was to compare a GnRH agonist and hCG as ovulation inducing agents to apply fixed-time insemination in ovsynch synchronized superovulated goats. Three groups of 17 does of the Boer goat breed were synchronized, superovulated and ovulation induced with a GnRH analog, hCG or physiological saline, followed by mating and non-surgical embryo collection. Part of the does were provided with subcutaneous progesterone implants after mating to compensate for frequently occurring premature corpus luteum regression. Estrus detection was conducted with aproned bucks, ovarian function was monitored sonographically and by progesterone analyses and blood samples were drawn to generate LH profiles. Practically all does responded to treatment and occurrence and duration of estrus as well as the ovulatory response were unaffected by treatment. The LH surge provoked by administration of the GnRH analog buserelin emerged within 1.0 h and was closely synchronized, significantly more so than after administration of hCG or physiological saline, commencing after 11.8 and 14.9 h, respectively, with no significant differences amongst each other. It would seem that hCG is not effective in bringing about a LH surge. The interval between commencement of the LH surge and ovulation was, across treatment groups, 24.2 h with no significant difference among groups. Ovulatory response and yield of transferable embryos obtained by nonsurgical collection were modest with no significant differences among groups.


Patterns of patient coping following hospital discharge from medical and surgical units: A pilot study.
A pilot study was conducted to determine the feasibility of a longitudinal investigation of patients' coping during the early postdischarge period. Recruitment was conducted on a general medical unit and a surgical orthopedic unit. Forty-four participants were recruited with 95% retention. Demographic characteristics plus measures of discharge risk and perceived readiness (expected coping) were collected before discharge. Measures of coping (experienced) and the use of supports and services were collected on the first day postdischarge, the end of the first week, and during weeks 3 and 5. Considerable variability was evident in coping scores, and not all participants exhibited improvement over time. Four patterns of coping were identified: ongoing recovery, initial shock, bumpy road, and progressive decline. Further investigation is required to validate the observed coping patterns. A better understanding of conditions affecting patient coping during the transition from hospital to home will support efforts to reduce unplanned use of acute care services.


Integrated analysis on biochemical profiling and transcriptome revealed nitrogen-driven difference in accumulation of saponins in a medicinal plant Panax notoginseng.
The medicinal plant Panax notoginseng is considered a promising source of secondary metabolites due to its saponins. However, there are relatively few studies on the response of saponins to nitrogen (N) availability and the mechanisms underlying the N-driven regulation of saponins. Saponins content and saponins -related genes were analyzed in roots of P. notoginseng grown under low N (LN), moderate N (MN) and high N (HN). Saponins was obviously increased in LN individuals with a reduction in β-glucosidase activity. LN facilitated root architecture and N uptake rate. Compared with the LN individuals, 2872 and 1122 genes were incorporated into as differently expressed genes (DEGs) in the MN and HN individuals. Clustering and enrichment showed that DEGs related to "carbohydrate biosynthesis", "plant hormone signal transduction", "terpenoid backbone biosynthesis", "sesquiterpenoid and triterpenoid biosynthesis" were enriched. The up-regulation of some saponins-related genes and microelement transporters was found in LN plants. Whereas the expression of IPT3, AHK4 and GS2 in LN plants fell far short of that in HN ones. Anyways, LN-induced accumulation of C-based metabolites as saponins might derive from the interaction between N and phytohormones in processing of N acquisition, and HN-induced reduction of saponins might be result from an increase in the form of β-glucosidase activity and N-dependent cytokinins (CKs) biosynthesis.


FpvIR control of fpvA ferric pyoverdine receptor gene expression in Pseudomonas aeruginosa: demonstration of an interaction between FpvI and FpvR and identification of mutations in each compromising this interaction.
FpvR is a presumed cytoplasmic membrane-associated anti-sigma factor that controls the activities of extracytoplasmic function sigma factors PvdS and FpvI responsible for transcription of pyoverdine biosynthetic genes and the ferric pyoverdine receptor gene, fpvA, respectively. Using deletion analysis and an in vivo bacterial two-hybrid system, FpvR interaction with these sigma factors was confirmed and shown to involve the cytoplasmic N-terminal 67 amino acid resides of FpvR. FpvR bound specifically to a C-terminal region of FpvI corresponding to region 4 of the sigma(70) family of sigma factors. FpvR and FpvI mutant proteins compromised for this interaction were generated by random and site-directed PCR mutagenesis and invariably contained secondary structure-altering proline substitution in predicted alpha-helices within the FpvR N terminus or FpvI region 4. PvdS was shown to bind to the same N-terminal region of FpvR, and FpvR mutations compromising FpvI binding also compromised PvdS binding, although some mutations had a markedly greater impact on PvdS binding. Apparently, these two sigma factors bind to FpvR in a substantially similar but not identical fashion. Intriguingly, defects in FpvR binding correlated with a substantial drop in yields of the FpvI and to a lesser extent PvdS sigma factors, suggesting that FpvR-bound FpvI and PvdS are stable while free and active sigma factor is prone to turnover.


Flexible nanofibrous membranes of dual metallic metal-organic framework with enhanced Lewis basic sites and high loading mass for efficient CO2 capture.
Excessive CO2 emissions and the resultant global warming present significant environmental challenges, posing threats to human health and public safety. Metal-organic frameworks (MOFs), known for their high specific area and large porosity, hold the promise for CO2 capture. However, a major obstacle is the low loading mass of MOFs and the limited interface affinity and compatibility between MOFs and substrates. In this study, we present an electrospinning-assisted in-situ synthesis dual metallic framework strategy for preparing flexible Zn/Co-ZIF nanofibrous membranes (NFMs). This method achieves the high loading mass of MOFs and introduces abundant Lewis basic sites, thereby enhancing the CO2 adsorption. The dual metallic Zn/Co-ZIF NFMs exhibit remarkable features, including high MOF loading mass (70.23 wt%), high specific surface area (379.63 m2g-1), large porosity (92.34 %), high CO2 adsorption capacity (4.43 mmol/g), high CO2/N2 adsorption selectivity (37), and high CO2/CH4 adsorption selectivity (31). Moreover, the dual metallic Zn/Co-ZIF NFMs demonstrate robust structural stability and durability attributed to the excellent interface affinity between MOFs and NFMs, retaining 96.56 % of their initial capacity after 10 adsorption-desorption cycles. This work presents a prospective direction for developing flexible dual metallic MOF NFMs for the efficient capture of CO2.


Effects of physical activity on initial level and response magnitude: an experimental study of the LIV.
Two exercise and two relaxation conditions were used to manipulate subjects' overall level of physical activity. A digit-transformation-and-recall task was administered under each of these four conditions in order to elicit physiological responses. Measures of prestimulus level and response magnitude were taken for each of six dependent variables: skin conductance (SC), heart rate (HR), finger pulse volume (PV), and three respiration indices. It was hypothesized that as the subject's degree of activity increased the physiological variables would show ergotropic changes in prestimulus level together with decreasing magnitudes of response to the digit task. The results provided a reasonable degree of support for these predictions. Evidence for concomitant changes in prestimulus level and response magnitude was consistent with Wilder's Law of Intial Value (LIV). There were some cases, however, where response magnitude showed a predicted effect of treatment in the absence of a difference in prestimulus level; these findings could not be explained by the traditional LIV model.


Facial bite wounds: management update.
Bite wounds are frequently located on the face; injuries inflicted by dogs are most common, especially in children. Bacteriology of infected dog and cat bite wounds includes Pasteurella multocida, Staphylococcus aureus, viridans streptococci, Capnocytophaga canimorsus, and oral anaerobes. Infected human bites yield a similar spectrum of bacteria except for Pasteurellae and C. canimorsus; instead human bites are frequently complicated by Eikenella corrodens. Antibiotic therapy against these bacteria is indicated both for infected bite wounds and fresh wounds considered at risk for infection. Amoxicillin-clavulanate (and other combinations of extended-spectrum penicillins with beta-lactamase inhibitors) and moxifloxacin offer the best in vitro coverage of the pathogenic flora. Initial wound management consisting in irrigation and debridement is at least equally important with antibiotics for prevention of infection. The need for prophylaxis against systemic infectious complications, particularly tetanus, should also be evaluated. Primary surgical repair is the treatment of choice for most clinically uninfected facial bite wounds, whereas delayed closure should be reserved for certain high risk or already infected wounds. Avulsive injuries with significant tissue loss represent the most difficult cases for definitive management and are also those most likely to require hospitalization.


Use of subcutaneous abdominal fat biopsy specimen for detailed typing of amyloid fibril protein-AL by amino acid sequence analysis.
A simple technique for the purification of amyloid fibril proteins from patients with systemic amyloidosis was used on a 45 year old woman. The method is based on the use of a surgical subcutaneous fat tissue biopsy specimen which was used for the characterisation of the amyloid as a kappa I AL-protein by amino acid sequence analysis. The method permits the exact typing of amyloid in many patients with systemic amyloidosis, which, until now has been almost exclusively confined to necropsy tissue.


Substitutions at residues 300 and 389 of the VP2 capsid protein serve as the minimal determinant of attenuation for canine parvovirus vaccine strain 9985-46.
Identifying molecular determinants of virulence attenuation in live attenuated canine parvovirus (CPV) vaccines is important for assuring their safety. To this end, we identified mutations in the attenuated CPV 9985-46 vaccine strain that arose during serial passage in Crandell-Rees feline kidney cells by comparison with the wild-type counterpart, as well as minimal determinants of the loss of virulence. Four amino acid substitutions (N93K, G300V, T389N and V562L) in VP2 of strain 9985-46 significantly restricted infection in canine A72 cells. Using an infectious molecular clone system, we constructed isogenic CPVs of the parental virulent 9985 strain carrying single or double mutations. We observed that only a single amino acid substitution in VP2, G300V or T389N, attenuated the virulent parental virus. Combinations of these mutations further attenuated CPV to a level comparable to that of 9985-46. Strains with G300V/T389N substitutions did not induce clinical symptoms in experimentally infected pups, and their ability to infect canine cells was highly restricted. We found that another G300V/V562L double mutation decreased affinity of the virus for canine cells, although its pathogenicity to dogs was maintained. These results indicate that mutation of residue 300, which plays a critical role in host tropism, is not sufficient for viral attenuation in vivo, and that attenuation of 9985-46 strain is defined by at least two mutations in residues 300 and 389 of the VP2 capsid protein. This finding is relevant for quality control of the vaccine and provides insight into the rational design of second-generation live attenuated vaccine candidates.


Resistance to nonnucleoside reverse-transcriptase inhibitors and prevalence of HIV type 1 non-B subtypes are increasing among persons with recent infection in Spain.
The prevalence of drug resistance mutations was 12.1% among 198 persons who experienced human immunodeficiency virus (HIV) seroconversion identified in Spain during 1997-2004. There was a significant increase of K103N and of non-B subtypes over time. Transmission of HIV infection around the time of seroconversion was shown in 8 couples and in 2 clusters of 3 individuals.


Platelet function suggests cardioembolic aetiology in cryptogenic stroke.
Platelet-monocyte (PMA) and platelet-neutrophil aggregations (PNA) play critical roles in the evolution of acute ischemic stroke (AIS). The present study investigates the mechanistic basis of platelet responsiveness in cryptogenic stroke compared with cardioembolic stroke. Platelet from 16 subjects, each from cryptogenic and cardioembolic stroke groups and 18 age-matched healthy controls were subjected to different investigations. Compared to healthy controls, platelet-monocyte and platelet-neutrophil interactions were significantly elevated in cryptogenic (2.7 and 2.1 times) and cardioembolic stroke (3.9 and 2.4 times). P-selectin expression on platelet surface was 1.89 and 2.59 times higher in cryptogenic and cardioembolic strokes, respectively, compared to healthy control. Cell population with [Ca2+i] in either stroke group was significantly outnumbered (by 83% and 72%, respectively, in cryptogenic and cardioembolic stroke) in comparison to healthy controls. Noteworthy, TEG experiment revealed that the cryptogenic stroke exhibited significant decline in Reaction Time (R) and amplitude of 20 mm (K) (by 32% and 33%, respectively) while thrombin burst (α-angle) was augmented by 12%, which reflected substantial boost in thrombus formation in cryptogenic stroke. Although TEG analysis reveals a state of hypercoagulability in patients with cryptogenic stroke. However, platelets from both stroke subtypes switch to a 'hyperactive' phenotype.


[Who reads the Revista Médica del IMSS? Altmetrics answer it].
The Revisa Médica del IMSS is considered a track of national and international scientific dissemination that presents the results of clinical research carried out within the Institute. Altmetrics, or alternative metrics, emerged as an alternative to citation-based metrics and allow authors to visualize the impact of their works that have not received citations to identify the characteristics of the readers who consult their published article. It is important that scientific journals have accurate information from their readers, as it will provide them with an overview of the use of the information produced in their area of expertise or in their institution. This editorial explores the characteristics of the readers of the Revista Médica del IMSS through the analysis of alternative metrics available in the Dimensions database.


Immuno-labelling for freeze-fracture: application to a cell surface attachment antigen.
The cell-surface attachment (CSAT) antigen was investigated by using a technique that combines freeze-fracture with thin-sectioning. Chick heart cells were labelled using colloidal gold secondary antibodies, then fractured and shadowed with platinum vapor. The cells were dehydrated and embedded with their gold labels and replicated surfaces still intact. Sectioning revealed gold particles superimposed with external (E) fracture faces. The gold was definitely not coincident with E face particles and did not appear to be associated with pits. Therefore, it can be concluded that the CSAT glycoproteins is not represented by an E face particle. Whether it may be seen as an E face pit, or is not visible at all in freeze-fracture, is still an open question.


Sex steroid hormones levels and testicular activity during hepatocarcinogenesis by N-2-fluorenylacetamide.
During hepatocarcinogenesis by N-2-fluorenylacetamide, the hormonal status of male Sprague-Dawley rats is modified. The testes present a reduced activity which is evidenced by a decreased spermatogenetic activity accompanied by a drastic decrease of the plasma testosterone level. In contrast, plasma progesterone and estradiol-17 beta levels were not modified despite the 80 fold augmentation of alpha-fetoprotein, an estrogen binding protein synthesized during liver carcinogenesis.


Label-free colorimetric sensor for ultrasensitive detection of heparin based on color quenching of gold nanorods by graphene oxide.
A novel label-free colorimetric strategy was developed for ultrasensitive detection of heparin by using the super color quenching capacity of graphene oxide (GO). Hexadecyltrimethylammonium bromide (CTAB)-stabilized gold nanorods (AuNRs) could easily self-assembly onto the surface of GO through electrostatic interaction, resulting in decrease of the surface plasmon resonance (SPR) absorption and consequent color quenching change of the AuNRs from deep to light. Polycationic protamine was used as a medium for disturbing the electrostatic interaction between AuNRs and GO. The AuNRs were prevented from being adsorbed onto the surface of GO because of the stronger interaction between protamine and GO, showing a native color of the AuNRs. On the contrary, in the presence of heparin, which was more easily to combine with protamine, the AuNRs could self-assembly onto the surface of GO, resulting in the native color disappearing of AuNRs. As the concentration of heparin increased, the color of AuNRs would gradually fade until almost colorless. The amounts of self-assembly AuNRs were proportional to the concentration of heparin, and thereby the changes in the SPR absorption and color had been used to monitor heparin levels. Under optimized conditions, good linearity was obtained in a range of 0.02-0.28 μg/mL (R=0.9957), and a limit of detection was 5 ng/mL. The simultaneous possession of high sensitivity and selectivity, simplicity, rapidity, and visualization enabled this sensor to be potentially applicable for ultrasensitive and rapid on-site detection toward trace heparin.


n-Butyl cyanoacrylate-induced multiple retinal arteriolar occlusions.
We report a case of multiple retinal arteriolar occlusions due to delayed embolisation of N-butylcyanoacrylate glue, initially injected in the external carotid artery for the management of Carotid body tumour. Ocular massage and anterior chamber paracentesis were unfruitful and patient suffered irreversible visual loss in the affected eye. Embolisation of N-butyl cyanoacrylate glue into the retinal vasculature after intratumoral injection should be kept in mind as a rare but possible complication by radiologists and ophthalmologists.


Placental volume, vasculature and calcification in pregnancies complicated by pre-eclampsia and intra-uterine growth restriction.
Pre-eclampsia (PET) and intrauterine growth restriction (IUGR), often associated with impaired placental function, are among the most common conditions contributing to increased perinatal mortality and morbidity. This study investigates if three dimensional power Doppler (3DPD) of the placenta and computerised analysis of placental calcification is different between PET/IUGR and normal pregnancies. This was a prospective cohort study involving 50 women with pre-eclampsia and/or IUGR, or with IUGR only from 24 to 40 weeks' gestation. 3DPD ultrasound was used to calculate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Following each scan the percentage of placental calcification was also calculated, by computer analysis. Results were compared with normal (control) values, and findings correlated with maternal and fetal Doppler parameters and placental histology. Volume, VI, and VFI are not influenced by gestational age in PET/IUGR pregnancies. FI was found to increase with gestational age (p=0.009) and was lower than normal in the total study group from 24 to 30 weeks (p=0.006). In the pregnancies affected by PET, whether or not IUGR was present, all three indices were lower than normal values between 24 and 30 weeks (VI: p=0.038, FI: p=0.004, VFI: p=0.015). Vascularisation and flow indices were less than the normal 50th centile in the majority of cases of utero-placental insufficiency (p=0.047), and vascularisation and vascularisation flow indices were lower in cases of accelerated placental maturation (p=0.016 and 0.041 respectively). Placental volume greater than the 50th centile between 24 and 30 weeks was associated with the presence of infarction on histology (p=0.021). Flow index (p=0.002) and vascularisation flow index (p=0.036) were lower in the presence of bilateral uterine artery notches. Calcification, similar to the control group, was related to an increasing UAPI (p=0.041) and MCA PI <5th centile (p=0.010). The study findings suggest that there may be a role for 3DPD placental assessment of volume, vascularisation and blood flow and computer analysis of placental calcification in the identification and management of PET/IUGR pregnancy.


ACTH-adrenal system and exogenous steroids.
The results obtained from a research on 100 patients of both sexes affected with bronchial asthma, chronic obstructive bronchopathy, rheumatoid arthritis, haematological disorders and some other pathological forms, all depending on steroid therapy, are reported in this paper. The treatment was carried out using a new chronopluricorticoid (Dutimelan 8 15). The clinical efficiency is comparable to that obtained by the traditional steroid treatment with the advantage that symptoms of hypercorticism were absent or insignificant. The authors believe that such excellent results are to be attributed to the particular chronopharmacological characteristics of this preparation.


Characterization of skeletal muscle insulin receptor.
The insulin receptor from rat skeletal muscle was characterized. Treatment of muscle membranes with the photoactive insulin analog, 125I[N-epsilonB29-monoazidobenzoyl]-insulin revealed a single protein band of 135,000 Da, the alpha subunit. Iodination of total membrane protein followed by Triton X-100 solubilization and immunoprecipitation demonstrated the presence of a protein band of 90,000 Da, the beta subunit, together with a protein band of 190,000 Da, which may be the receptor precursor. In partially purified receptor preparations, the beta subunit exhibited dose-dependent, insulin-stimulated phosphorylation with incorporation of phosphate solely into tyrosine residues, which was also observed in the 190,000-Da receptor precursor. Purified plasma membranes contained a large amount of insulin-degrading activity which had to be inactivated prior to performing insulin-binding studies. If degradation of insulin was not prevented, apparent enhanced binding in the presence of unlabeled insulin was observed.


A closer look revisited: are we subjects or are we donors?
The author offers personal reflections on the implications of the article "Managing Incidental Findings & Research Results in Genomic Research Involving Biobanks & Archived Datasets" in terms of how the article addresses serious knowledge disparities and differing expectations between participants and researchers.Genet Med 2012:14(4):458-460.


[New diagnostic methods for bacterial infections after the introduction of increased bioterrorism preparedness].
Bacillus anthracis, Francicella tularensis, Yersinia pestis, Burkholderia pseudomallei and Brucella melitensis are the bacteria most often mentioned in connection with possible biological terrorist acts. It is known that these microorganisms can be cultured and weaponised for such a purpose. This survey provides examples of the use of diagnostic methods for those microorganisms, further detailed in relation to establishing a national center for biological preparedness in Denmark.


Steady-state kinetic studies of the metal ion-dependent decarboxylation of oxalacetate catalyzed by pyruvate kinase.
Steady-state kinetic studies with differing divalent metals ions have been carried out on the pyruvate kinase-catalyzed, divalent cation-dependent decarboxylation of oxalacetate to probe the role of the divalent metal ion in this reaction. With either Mn2+ or Co2+, initial velocity patterns show that the divalent metal ion is bound to the enzyme in a rapid equilibrium prior to the addition of oxalacetate. Further, there is no change in the initial velocity patterns or the kinetic parameters in the presence or absence of K+, indicating that K+ is not required for oxalacetate decarboxylation. Dead-end inhibition of the decarboxylation reaction by the physiological substrate phosphoenolpyruvate indicates that phosphoenolpyruvate binds only to the enzyme-metal ion complex and not to free enzyme. The pKi values for both Mn2+ and Co2+ decrease below a pK of 7.0, and increase above a pK of 8.9. Since these pK values are the same for both ions, both of the observed pK values must be attributable to enzymatic residues. The pK of 7.0 is presumably that of a ligand to the metal ion, while the pK of 8.9 is probably that of the lysine involved in enolization of pyruvate in the normal physiological reaction. However, with Co2+ as divalent cation, the V for oxalacetate decreases above a pK of 8.0, the V/K decreases above two pK values averaging 7.8, and the pKi for oxalate decreases above a single pK of 7.3. These data indicate that metal-coordinated water is displaced during the binding of substrates or inhibitors and the other pK value observed in both V and V/K pH profiles (pK of 8.3 with Co2+ and 9.2 with Mg2+) is an enzymatic residue whose deprotonation disrupts the charge distribution in the active site and decreases activity.


Development of a Pathomics-Based Model for the Prediction of Malignant Transformation in Oral Leukoplakia.
Accurate prognostic stratification of oral leukoplakia (OLK) with risk of malignant transformation into oral squamous cell carcinoma is crucial. We developed an objective and powerful pathomics-based model for the prediction of malignant transformation in OLK using hematoxylin and eosin (H&E)-stained images. In total, 759 H&E-stained images from multicenter cohorts were included. A training set (n = 489), validation set (n = 196), and testing set (n = 74) were used for model development. Four deep learning methods were used to train and validate the model constructed using H&E-stained images. Pathomics features generated through deep learning combined with machine learning algorithms were used to develop a pathomics-based model. Immunohistochemical staining of Ki67, p53, and PD-L1 was used to interpret the black box of the model. Pathomics-based models predicted the malignant transformation of OLK (validation set area under curve [AUC], 0.899; testing set AUC, 0.813) and significantly identified high-risk and low-risk populations. The prediction performance of malignant transformation from dysplasia grading (validation set AUC, 0.743) was lower than that of the pathomics-based model. The expressions of Ki67, p53, and PD-L1 were correlated with various pathomics features. The pathomics-based model accurately predicted the malignant transformation of OLK and may be useful for the objective and rapid assessment of the prognosis of patients with OLK.


Interactome analysis reveals versatile functions of Arabidopsis COLD SHOCK DOMAIN PROTEIN 3 in RNA processing within the nucleus and cytoplasm.
Arabidopsis COLD SHOCK DOMAIN PROTEIN 3 (AtCSP3) shares an RNA chaperone function with E. coli cold shock proteins and regulates freezing tolerance during cold acclimation. Here, we screened for AtCSP3-interacting proteins using a yeast two-hybrid system and 38 candidate interactors were identified. Sixteen of these were further confirmed in planta interaction between AtCSP3 by a bi-molecular fluorescence complementation assay. We found that AtCSP3 interacts with CONSTANS-LIKE protein 15 and nuclear poly(A)-binding proteins in nuclear speckles. Three 60S ribosomal proteins (RPL26A, RPL40A/UBQ2, and RPL36aB) and the Gar1 RNA-binding protein interacted with AtCSP3 in the nucleolus and nucleoplasm, suggesting that AtCSP3 functions in ribosome biogenesis. Interactions with LOS2/enolase and glycine-rich RNA-binding protein 7 that are cold inducible, and an mRNA decapping protein 5 (DCP5) were observed in the cytoplasm. These data suggest that AtCSP3 participates in multiple complexes that reside in nuclear and cytoplasmic compartments and possibly regulates RNA processing and functioning.


Dynamic ultrasonographic sign for posterior shoulder dislocation.
Acute posterior shoulder dislocation is rare, and its early diagnosis remains a challenge to the emergency physician. This report describes two cases of acute posterior shoulder dislocation confirmed by bedside ultrasound scan performed by the emergency physician. Bedside ultrasound for diagnosis of posterior shoulder dislocation is accurate, noninvasive, repeatable, convenient, and without ionizing radiation. Dynamic ultrasound sign of posterior shoulder dislocation and using bedside ultrasound for verification of successful reduction of posterior shoulder dislocation are described.


Bis[μ3-2-(pyridin-3-yl)acetato-κ3 O:O:O']bis-[μ2-2-(pyridin-3-yl)acetato-κ2 O:O']bis-[chlorido-(1,10-phenanthroline-κ2 N,N')dysprosium(III)].
The title DyIII complex, [Dy2(C7H6NO2)4Cl2(C12H8N2)2] or [Dy2(μ 3-PAA)4(Cl)2(phen)2] (PAA = 3-pyridyl-acetate, phen = 1,10-phenanthroline), obtained by reaction of Dy(ClO4)3, 3-pyridyl-acetic acid ligands and 1,10-phenanthroline, exhibits a dinuclear structure. Adjacent binuclear dimers are further connected via face-to-face π-π stacking inter-actions resulting in supra-molecular chains along the c-axis direction.


The Experience of Virtual Interviews in Resident Selection: A Survey of Program Directors in Surgery.
MATCH 2021 was short of the classic "in-person" component. Herein, we assess the impact of virtual interviews (VIs) on resident selection, from the perspectives of program directors (PDs) across all surgical specialties. We conducted a cross-sectional survey-based study of ACGME-accredited US residency program directors (PDs) of all surgical specialties. The survey was designed based on a review of relevant literature and inquired about the strengths, limitations, and overall utility of VIs. A total of 365 PDs responded to our survey. Almost all respondents (90%) found VIs to be less expensive than in-person interviews, while only 34% agree that VIs were less time-consuming. Only a median of 5% of interviews was complicated by technical difficulties. Most PDs found it more challenging to assess applicants' fit (75%), personality and communication skills (71%), and commitment to specialty (60%). Only 14% found VIs to be overall better for assessing residency applicants. In future cycles, most PDs are planning to host both virtual and in-person interviews (57%), while 35% and 8% will host exclusive in-person and virtual interviews, respectively. VIs are a novel way of dealing with the restrictions imposed by COVID-19. Despite their cost and time benefit, they present particular challenges in evaluating residency applicants. A combination of both virtual and in-person interviews will likely be implemented in the coming cycles.


Diastereomeric resolution of nucleoside analogues, new potential antiviral agents, using high-performance liquid chromatography on polysaccharide-type chiral stationary phases.
This paper describes the separation of the four sets of stereoisomers of nucleoside analogs, new potential antiviral agents by direct analytical HPLC methods using derivatized cellulose and amylose chiral stationary phases. The resolution was made using normal-phase methodology with a mobile phase consisting of n-hexane-alcohol (ethanol or 2-propanol) in various percentages, and a silica-based cellulose tris-3,5-dimethylphenylcarbamate (Chiralcel OD-H), or tris-methylbenzoate (Chiralcel OJ) and a silica-based amylose tris-3,5-dimethylphenylcarbamate (Chiralpak AD) or tris-(S)-1-phenylethylcarbamate (Chiralpak AS). The effects of structural features on the extent of discrimination between the stereoisomers were examined through the retention, the selectivity and the resolution factors as well as the elution order. Baseline separation (Rs>1.5) was easily obtained in many cases. The resolution results were complementary between the different columns.


Amygdala or ventral hippocampal lesions at two early stages of life differentially affect open field behaviour later in life; an animal model of neurodevelopmental psychopathological disorders.
Psychiatric disorders like schizophrenia or autism are thought to result from disruption of the normal pattern of brain development. Abnormalities in the amygdaloid complex and hippocampus have been reported in these disorders. In the present study rats were lesioned in the amygdala or ventral hippocampus on day 7 of life (immature brain) or day 21 of life (almost mature brain) and open field behaviour was determined later in life before and after puberty. Lesioning on day 7 resulted in behavioural changes, interpreted as locomotor stereotypy and decreased anxiety in case of amygdala or hippocampus, respectively. These effects were more profoundly present after puberty. Lesioning on day 21 did not result in these behavioural changes, which subscribes to the importance of the stage of brain maturation on functional development. The results suggest that the behavioural changes in rats lesioned on day 7 may due to a malfunctioning of structures connected to the amygdala or ventral hippocampus. Brain lesions made on day 7 of life may serve as a potential model of psychopathological neurodevelopmental disorders.


Plexiform neurofibroma with neurofibromatosis type I/ von Recklinghausen's disease: A rare case report.
Plexiform neurofibroma with neurofibromatosis type 1 (NF1) or Von Recklinghausen's disease is a rare entity and occurs in approximately 5-15% patients. These are slow growing, painless and locally infiltrating tumors. The pattern of inheritance is autosomal dominant and its penetrance is almost complete by 5 years of age. We hereby report a case of 13 years old boy visited presenting with swelling of right eyelid and forehead. After surgical removal, the tissue was sent for histopathological evaluation. Microscopy revealed an unencapsulated tumor mass comprising of well organized mixture of multiple nerve bundles with interlacing neural tissue in background of spindle shaped cells along with myxoid areas and numerous blood vessels. The NF1 gene responsible for the disease is located on chromosome 17 at locus 17q11.2 that codes for the protein neurofibromin. The frequency of neomutations is particularly high and almost half of the cases are sporadic. NF1 is characterized by a wide variability of clinical expressions, even within a given family. Majority of patients can be diagnosed only after thorough physical examination. The wide variation of the clinical expression, the tumor risk and the totally unpredictable evolution of the disease impose regular monitoring of NF1 patients. This surveillance is mainly clinical and has to be adapted to the patient's age in order to assure early management of complications.


Association of genomic variants at the human leukocyte antigen locus with cervical cancer risk, HPV status and gene expression levels.
The human leukocyte antigen (HLA) locus on chromosome 6 has been reported to be associated with cervical cancer. We investigated two independent single-nucleotide polymorphisms in a large case-control series of cervical dysplasia and carcinoma that has been newly established by the German Cervigen Consortium, comprising a total of 2481 cases and 1556 healthy females. We find significant associations for both variants, rs9272117 at HLA-DQA1 and rs2844511 at MICA and HCP5, with cervical disease. Both variants showed evidence of association with invasive cervical cancer (rs9272117: OR 0.89, 95% CI 0.79-0.99, P = .036; rs2844511: OR 1.17, 95% CI 1.04-1.31, P = .008) and with high-grade dysplasia (rs9272117: OR 0.78, 95% CI 0.70-0.87, P = 7.1 × 10-6 ; rs2844511: OR 1.13, 95% CI 1.01-1.26, P = .035), as well as in a combined analysis of both groups (rs9272117: OR 0.83, 95% CI 0.75-0.91, P = 6.9 × 10-5 ; rs2844511: OR 1.14, 95% CI 1.04-1.26, P = .005). Variant rs2844511, but not rs9272117, also showed modest evidence of association with low-grade dysplasia (OR 1.26, 95% CI 1.04-1.54, P = .019). In case-only analyses, rs2844511 tended to predict HPV status (P = .044) and rs9272117 tended to associate with HPV16 (P = .022). RNA studies in cervical samples showed a significant correlation in the transcript levels of MICA, HCP5 and HLA-DQA1, suggesting extensive co-regulation. All three genes were upregulated in HPV16-positive samples. In stratified analyses, rs9272117 was associated with HLA-DQA1 levels, specifically in HPV-positive samples, while rs2844511 was associated with MICA and HCP5 levels. The risk allele of rs2844511 was required for correlations between MICA or HCP5 with HLA-DQA1. Altogether, our results support 6p21.32-33 as the first consistent cervical cancer susceptibility locus and provide evidence for a link between genetic risk variants, HPV16 status and transcript levels of HLA-DQA1, HCP5 and MICA, which may contribute to tumor immune evasion.


Proteomic changes occurring along gonad maturation in the edible sea urchin Paracentrotus lividus.
The reproductive stage of Paracentrotus lividus strongly influences product quality that, in turn, impacts significantly on the market price. Large, compact and sweet gonads are preferred, and sensory attributes are positively related to the ratio of nutritive phagocytes to gametes. Gonads at advanced maturation stages, although larger, have less desirable attributes, being more watery and bitter especially in females. Therefore, the best compromise among size, texture, and taste needs to be reached. In this study, wild P. lividus were collected along coastal Sardinia, and gonads in the recovery, pre-mature, mature, and spent stages were analyzed by gel-based and by shotgun proteomics. A detailed characterization of the proteome changes occurring in gonads of both sexes along maturation was achieved, and significant modifications were seen in numerous proteins involved in nutrient accumulation in nutritive phagocytes, as well as in gamete biology and maturation. Adding to an improved understanding of the P. lividus reproductive cycle in its natural environment, the results described in this work may form the basis for defining novel protein markers and procedures for an easier sexing and staging, and for monitoring sea urchin gonad maturation cycles in aquaculture plants. Mass spectrometry data are deposited in ProteomeXchange (PXD004200). The sensory quality of P. lividus gonads is strongly influenced by the reproductive cycle, with significant changes in flavor, texture, and size. A better knowledge of the protein profiles, patterns, and markers associated with gonad sex and maturation stage can have useful implications for understanding and monitoring these changes. One of these is the ability to identify protein profiles specifically associated with a given stage and, in perspective, to identify maturation and sex markers. The comprehensive proteomic evaluation achieved in this work was made possible by the application of combined gel-based and shotgun approaches. As a result, this study generated the largest proteomic dataset available in the literature for P. lividus, as well as a general picture of protein abundance changes occurring along maturation.


Baricitinib is potentially effective in the treatment of refractory livedoid vasculopathy.
Livedoid vasculopathy is a rare, chronic, and recurrent disease with limited effective treatments. Its etiopathogenesis remains incompletely understood. Baricitinib, a selective Janus kinase 1 and 2 inhibitor, has been used to treat rheumatoid arthritis and could reduce the disease severity in patients with livedoid vasculopathy. We retrospectively observed eight patients who received 2 mg/day of baricitinib for the treatment of refractory livedoid vasculopathy. We evaluated their clinical scores before and after treatment to determine its effectiveness and safety. Improvement in livedoid vasculopathy was observed with significant regression in the clinical scores after baricitinib treatment. The mean clinical scores were 7.0 ± 1.6 and 1.4 ± 1.2 before and after baricitinib treatment, respectively (P <0.01). Furthermore, six out of the eight patients achieved a clinical score of 0 or 2 after treatment. These scores indicated remission. Clinical findings, including erythema, ulceration, and pain, improved in all the patients. The remission times ranged from 3 to 13 weeks, with a mean remission time of 7.75 ± 3.45 weeks. There were no reports of adverse events in any patient. Our study showed that baricitinib treatment was safe and could significantly relieve the signs and symptoms of livedoid vasculopathy. However, randomized controlled studies should be conducted to confirm these results.


Identification of MCM4 as a Prognostic Marker of Hepatocellular Carcinoma.
MCM4 expression difference in HCC were analyzed from TCGA and GEO data and verified by real-time PCR and western blot. ROC curve was used to analyze the diagnostic value of MCM4 and AFP. Additionally, the relationship between MCM4 and stage or nodal metastasis status or grade or age in TCGA cohort with HCC was observed from the UALCAN website. The univariate and multivariate Cox and functional analyses were done to explore the prognostic value of MCM4 in TCGA cohort. It was found that MCM4 was significantly highly expressed in HCC tissues from TCGA, GEO, and experimental data. Furthermore, ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA (AUCMCM4 = 0.9461, AUCAFP = 0.7056) and GEO (GSE19665: AUCMCM4 = 0.8800, AUCAFP = 0.5100; GSE64041 AUCMCM4 = 0.8038, AUCAFP = 0.6304). AUC of MCM4 from real-time PCR result in 60 pairs of HCC and adjacent tissues was 0.7172, demonstrating the prediction value of MCM4. Besides, different expression tendencies of MCM4 among different stages or nodal metastasis status or grade or age were observed from the UALCAN website. In addition, multiROC analysis showed the advantage of MCM4 as a survival prediction at 1, 3, and 5 years with the higher AUC at 0.69 of 1 year, 0.65 of 3 years, and 0.61 of 5 years. It was shown that MCM4 was independently associated with OS in univariate and multivariate Cox analysis. And GSEA displayed that MCM4 was highly enriched in KEGG_CELL_CYCLE signaling pathway following higher correlation positively with CDC6, PLK1, CRC1, and BUB1B in HCC. MCM4 might be a potential biomarker in guiding the prognostic status of HCC patients.


Avian sympathetic cardiac fibers and their cells of origin: anatomical and electrophysiological characteristics.
The sympathetic cardiac innervation of the pigeon was investigated to describe certain anatomical and physiological properties of the cardiac nerve fibers and their postganglionic cells of origin. The compound action potential of the right cardiac nerve has two major components, one conducting at 2.0-5.6 m/sec with no chronotropic effect on the heart and the other conducting at 0.4-1.0 m/sec with a cardioacceleratory effect. Postganglionic neurons responding antidromically to cardiac nerve stimulation were then studied in ganglion 14 which contains most cells of origin of the cardiac fibers. These neurons have refractory periods of approximately 4 msec, following frequencies of less than 4 HZ, and axons conducting at 0.4-2.0 m/sec; this conduction velocity range corresponds to the slower compound action potential component. Electron microscopy of the cardiac nerve revealed unmyelinated fibers ranging in diameter from 0.2 to 1.2 micrometer and a population of myelinated fibers 1.0-3.6 micrometer in diameter. The unmyelinated fibers account for the slower compound action potential component and are largely postganglionic cardioaccelerator axons. The myelinated fibers account for the faster compound action potential component which has no chronotropic effect and is not reflected in postganglionic antidromic latencies; it is suggested that these myelinated fibers are cardiac sympathetic afferents. This study thus establishes electrophysiological criteria for identifying cardiac postganglionic neurons and describes the anatomical basis of these criteria.


An umbrella review of intersectoral and multisectoral approaches to health policy.
Despite the widespread acceptance of the need for intersectoral and multisectoral approaches, knowledge around how to support, achieve, and sustain multisectoral action is limited. While there have been studies that seek to collate evidence on multisectoral action with a specific focus (e.g., Health in All Policies [HiAP]), we postulated that successes of working cross-sectorally to achieve health goals with one approach can glean insights and perhaps translate to other approaches which work across sectors (i.e., shared insights across HiAP, Healthy Cities, One Health, and other approaches). Thus, the goal of this study is to assemble evidence from systematic approaches to reviewing the literature (e.g., scoping review, systematic review) that collate findings on facilitators/enablers of and barriers to implementing various intersectoral and multisectoral approaches to health, to strengthen understanding of how to best implement health policies that work across sectors, whichever they may be. This umbrella review (i.e., review of reviews) was informed by the PRISMA guidelines for scoping reviews, yielding 10 studies included in this review. Enablers detailed are: (1) systems for liaising and engaged communication; (2) political leadership; (3) shared vision or common goals (win-win strategies); (4) education and access to information; and (5) funding. Barriers detailed were: (1) lack of shared vision across sectors; (2) lack of funding; (3) lack of political leadership; (4) lack of ownership and accountability; and (5) insufficient and unavailable indicators and data. These findings provide a rigorous evidence base for policymakers to inform intersectoral and multisectoral approaches to not only aid in the achievement of goals, such as the Sustainable Development Goals, but to work towards health equity.


Water-lifting aerator reduces algal growth in stratified drinking water reservoir: Novel insights into algal metabolic profiling and engineering applications.
Water-lifting aerator (WLA) which was developed by Professor Tinglin Huang at Xi'an University of Architecture and Technology, China has multi-functional water quality improvement that significantly inhibits the occurrence of harmful algal blooms (HABs) in deep drinking water reservoirs. However, the biological mechanism of WLA to the suppress algal growth has not been comprehensively understood. Here, the cellular mechanism that allows WLA to control HABs was explored based on the combination of both laboratory simulation and field investigation. Under simulated hydrodynamic conditions, the results showed that the cell density, chlorophyll a content, chlorophyll fluorescence parameters, and dehydrogenase activity in Microcystis aeruginosa all peaked under light conditions at 25 °C. The metabolic activity of M. aeruginosa varied significantly under low temperature at 6 °C and light conditions when cultured for 48 h. The extracellular organic matter (EOM) and intracellular organic matter (IOM) contents of M. aeruginosa were both resolved into three components. Moreover, the total fluorescence intensities from EOM and IOM both peaked under light conditions at 25 °C. The field investigation showed that the growth of algae was decreased significantly in Lijiahe drinking water reservoir with WLA application. The chlorophyll fluorescence parameters decreased significantly after vertical mixing, thereby indicating that the WLA weakened the photosynthetic ability and reduced the biological activity of algae in situ. In addition, the WLA significantly affected the vertical distribution of the phytoplankton community composition. Altogether, these results shed new lights on understanding the control of algal blooms by WLA in stratified drinking water reservoirs. WLA has broad prospect of engineering applications, which can control algal blooms of water supply resources in situ, therefore, reduce the content of disinfection by-products in drinking water treatment plants.


Role of interchain disulfide bonds on the assembly and secretion of human fibrinogen.
The cysteines involved in joining the 2 half-molecules of fibrinogen and also those located on either side of the alpha-helical coiled-coil region, were substituted, by site-directed mutagenesis, with serine. Fibrinogen assembly and secretion were determined in transiently transfected COS cells. Our studies indicate that in order to assemble the 2 half-molecules into a dimer, it is not sufficient to only have the disulfide linkages which keep the 2 half-molecules intact. The disulfide rings which flank the coil-coiled region also play important roles in dimer assembly. Intact interchain disulfide linkages at the NH2-terminal end of the coiled-coil region are essential for assembly of the 2 half-molecules. Disruption of these disulfide rings leads to the formation and secretion of half-molecules. Disruption of the interchain disulfide rings at the COOH-terminal end of the coiled-coil region allows dimer formation, but the 6-chain molecule which is assembled is not secreted. Disruption of both disulfide rings at either end of the coiled-coil region disallows assembly of half-molecules and of dimeric fibrinogen.


Availability of lysophosphatidylcholine in single bilayer vesicles for hydrolysis by lysophospholipase.
Single bilayer vesicles were prepared from total rat liver microsomal lipids to which 5 mol% lysophosphatidylcholine had been added. The availability of lysophosphatidylcholine for enzymatic hydrolysis by lysophospholipase (EC 188.8.131.52) was found to be higher in vesicles prepared by the cholate dispersion technique when compared with sonicated vesicles. Sepharose 4 B chromatography showed that the vesicles prepared by the cholate technique were smaller than those prepared by sonication. This is in contrast to previous observations for egg phosphatidylcholine vesicles. Total rat liver microsomal extracts were found to contain proteolipid, which could be removed by ether precipitation. Cholate vesicles prepared from proteolipid-free extracts were still smaller than sonicated vesicle from this extract. Experiments with [14C] dextran entrapped in the vesicles indicate that there is no loss of the permeability barrier of the vesicles for high molecular weight solutes during vesicle treatment with lysophospholipase. The high availability of lysophosphatidylcholine in cholate vesicles of total rat liver microsomal lipids is discussed in terms of a highly asymmetric distribution of lysophosphatidylcholine over the inner and outer monolayer of the bilayer.


Detection and quantification of 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine by electrospray ionization tandem mass spectrometry.
A novel and rapid method for identifying and quantifying 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3; reverse T3) has been introduced using electrospray ionization tandem mass spectrometry (ESI-MS/MS). MS(2) spectra in either negative ionization mode or positive ionization mode can be used to differentiate T3 and rT3. Quantification of the T3 and rT3 isomers under the negative ionization mode is also achieved without prior separation by HPLC.


Rater reliability of the adapted scoring criteria of the Minnesota Handwriting Assessment for children with cerebral palsy.
Current handwriting assessment tools are standardised mostly on typically developing students. This study estimated the intrarater and interrater reliabilities of the adapted scoring criteria, titled the Minnesota Handwriting Assessment-Cerebral Palsy (MHA-CP), for evaluating the effectiveness of handwriting interventions for children with cerebral palsy. We scored two batches of 20 random samples each from 80 handwriting samples produced by 30 children with cerebral palsy using the MHA-CP to estimate the intrarater and interrater reliabilities, respectively. Intraclass correlation coefficients exceeded 0.95 for both intrarater and interrater reliabilities for all quality subscales of the MHA-CP. The MHA-CP is shown to be a reliable measure of the manuscript handwriting performance of children with cerebral palsy who are in Grades 1 and 2. Further empirical testing is recommended to confirm its validity as an outcome measure for this population.


Influence of the ionic dialysance monitor on Kt measurement in hemodialysis.
Ionic dialysance can provide accurate monitoring of dialysis dose during each hemodialysis session. Increasingly, hemodialysis machines incorporate devices that measure ionic dialysance, allowing the dialysis dose to be determined noninvasively in real time and in each session. Because Kt product was proposed as a measure of hemodialysis dose to avoid the reverse J-shaped curve between urea reduction ratio or Kt/V and mortality, we investigated whether ionic dialysance values and Kt measurements are affected by different ionic dialysance monitors (Diascan and online clearance monitoring [OCM]) and dialysis machines. Four-period crossover. 31 adult long-term hemodialysis patients using 2 different ionic dialysance monitors in 4 dialysis machines: Diascan in Hospal Integra and Gambro AK-200 machines and OCM in Fresenius 4008S and 5008 machines. Ionic dialysance monitor and machine used in 4 hemodialysis sessions for each participant. Kt and Kt/V measured by using ionic dialysance and serum urea nitrogen. Mean values for initial and final ionic dialysance were similar for Integra and AK-200 machines, both measured by using Diascan, and for the 4008S and 5008 machines, both measured by using OCM; however, OCM values tended to be greater in the 4008S and 5008 machines. Kt measured in the 4008S and 5008 machines was greater (59.6 +/- 12 and 58.6 +/- 11 L, respectively) than with the Integra and AK-200 machines (53.4 +/- 11 and 53.8 +/- 11 L). Mean urea reduction ratio and Kt/V were 78.0% +/- 8% and 1.89 +/- 0.43 for Diascan monitors and 79.6% +/- 8% and 1.99 +/- 0.44 for OCM monitors, respectively (P < 0.01). Differences between monitors in Kt determination were caused in part by a real difference in dialysis effectiveness (6%) and in part by an intermethod difference (4%). Kt adjusted by Kt/V differences was recalculated, and because of good correlation between Diascan and OCM, we were able to apply a formula (Kt(OCM) = 1.08 Kt(Diascan) - 2; r =0.95) that allowed both Kt quantification methods to be compared. Nonblinded nonrandomized small sample. Kt is a valid method for judging dialysis dose in real time by using ionic dialysance measurements. Adjustments to correct intermethod differences may be necessary to ensure generalizability among ionic dialysance monitors.


Patients With Cirrhosis Have Elevated Bone Turnover but Normal Hepatic Production of Osteoprotegerin.
Severe osteodystrophy is common in patients with liver dysfunction. Markers of bone metabolism may help in early diagnosis of osteodystrophy and in understanding underlying pathophysiological mechanisms. To elucidate changes in bone metabolism associated with cirrhosis and to determine the route of elimination for the markers. Case-control study at a public university hospital. Fifty-nine patients with cirrhosis (47 alcoholic and 12 nonalcoholic cirrhosis) and 20 controls were included. Participants underwent catheterization of the femoral artery, and the hepatic, renal, and femoral veins with collection of blood from all 4 sites. Regional arteriovenous differences in concentrations of bone metabolism markers were determined: procollagen of type I collagen propeptide (PINP), C-terminal cross-linking telopeptide of type I collagen (CTX), osteocalcin, tartrate-resistant acid phosphatase isoform 5b (TRAcP5b), osteoprotegerin (OPG), and sclerostin and correlated with degree of disease (Child-Pugh classification). PINP concentration was higher (median: 87.9 µg/L) in patients with cirrhosis than in controls (52.6 µg/L) (P = .001), while hepatic extraction was lower (4.3% vs 14.5%) (P < .001). Both CTX and TRAcP5b were higher in patients with cirrhosis (340 ng/L and 3.20 U/L) than in controls (215 ng/L and 1.60 U/L) (P < .001 and P < .0001). Hepatic sclerostin extraction was lower in patients with cirrhosis (14.6%) than in controls (28.7%) (P < .0001). In both groups OPG showed a hepatic release rate (production) of 6%. Patients with cirrhosis have increased bone resorption, but unaltered bone formation. Sclerostin is eliminated through the liver while OPG is produced in the liver. Bone markers may prove useful in evaluating bone turnover in patients with cirrhosis.


Stochastic studies of aging and mortality in multicellular organisms. II. The finite theory.
We extend the development of a quantitative phenomenological theory of aging rooted in order theory. An organism is represented abstractly by a chain with a finite number of links. Each link corresponds to a possible rate-limiting event or process in senescence. A link is said to break when the corresponding event occurs or the corresponding process goes to completion. The chain is said to break, and the organism subsequently to perish, when the first link breaks, whichever link that might be. Two models are introduced to describe the failure of an arbitrary link. The first requires that a link break only after sustaining a fixed amount of deterioration; the second associates a non-zero probability of failure with each level of wear. The net deterioration of an intact chain is taken, crudely, to correspond to the decline in physiological vitality sustained by an organism during senescence. Failure of an arbitrary link is described in both models by a Markov process. The corresponding mortality rate derived in each instance describes aspects of available empirical data which cannot be accounted for by either the Gompertz or power-law relations. The decline in vitality is shown in both cases to be linear over time intervals of practical interest. The influence of temperature on the senescence of poikilotherms is briefly examined. We describe the effect of temperature both on longevity and the decline in vitality; indicate how substantial discrepancies can arise in the calculation of a macroscopic, effective, activation enthalpy; and lend theoretical support to the existence of temperature--memory effects in senescence.


Prediction of a high-risk group based on postoperative nadir CA-125 levels in patients with advanced epithelial ovarian cancer.
We aimed to determine the ideal cut-off of nadir serum CA-125 level for prediction of progression free survival. Among 267 patients who achieved complete remission after chemotherapy, the correlation between nadir CA-125 and progression free survival were compared among the subgroups classified according to the distribution of CA-125. The diagnostic odds ratio and area under the receiver operator characteristics curve were compared at various cut-off points. The nadir CA-125 levels did not have prognostic value under 12 U/mL (to 75 percentile). In contrast, they were significantly correlated with progression free survival only when the CA-125 level was greater than 12, which was 75 percentile (p=0.034). In predicting progression free survival <6 and 12 months, the cut-off value of 18 (90 percentile) showed superior diagnostic performance over 10 or 12 U/mL. Compared with patients who showed nadir levels between 0 and 12 U/mL (0 to 75 percentile), those with nadir >18 U/mL showed a hazard ratio of 2.85 (95% confidence interval, 1.70 to 4.76; p<0.001); patients with nadir levels between 18 and 12 U/mL showed a the hazard ratio of 1.68 (95% confidence interval, 1.11 to 2.56; p=0.015) compared with those whose nadir levels were under 12 U/mL. The predictive power of the traditional cut-off of 10 U/mL to classify a risk group or to identify high risk patients was unsatisfactory. The optimal diagnostic performance was observed at the cut-off of 18 U/mL and this can be proposed to dichotomize cut-off values to predict outcomes among individual patients.


Treatment-related adverse events as surrogate to response rate to immune checkpoint blockade.
Immune checkpoint blockade (ICB) brings hope to many late-stage cancer patients yet its marker for response remains elusive. We developed a hypothesis that treatment-related adverse events (TrAEs) could predict objective response rate (ORR) to ICB. We plotted ORR against corresponding any and grade 3 to 5 (G3-5) TrAEs across a variety of cancer types by performing a meta-analysis using linear regression. We identified 113 eligible studies encompassing 25 types of malignancies that were treated with ICB or ICB-based regimes. A significant linear correlation was observed for any and severe TrAEs, respectively. The correlation coefficient was 0.57 (r = 0.324) for any TrAE and 0.61 (r = 0.37) for G3-5 TrAE. For melanoma, the correlation coefficient was 0.81 (r = 0.57) for any TrAE and 0.65 (r = 0.42) for G3-5 TrAEs. For RCC, the correlation coefficient was 0.86 (r = 0.74) for any TrAE and 0.91 (r = 0.83) for G3-5 TrAE. For NSCLC, the correlation coefficient was 0.55 (r = 0.3) for any TrAE and 0.74 (r = 0.86) for G3-5 TrAE. For UC, the correlation coefficient was 0.47 (r = 0.68) for any TrAE and 0.27 (r = 0.52) for G3-5 TrAE, yet the correlation was insignificant for severe AEs. Our findings suggest that over half of ICB responses could be reflected by any adverse events and ∼60% of responses could be reflected by severe AEs. Further validation is needed in individual trials.


[Acute fatal copper intoxication. Casuistic and considerations on differential diagnosis (author's transl)].
If the diagnosis of copper-intoxication cannot be made by determination of copper in the collected specimen of the intestine, there may be problems in the differential diagnosis. In Wilson's disease and other cases of symptomatical hypercupriaemia copper content of brain tissues is elevated, while it is normal in acute copper intoxication.


Characterization of relaxin radioimmunoassay using Bolton-Hunter reagent. First results in plasma during pregnancy, and in placenta, corpora lutea and ovarian cysts in woman.
Application of a porcine relaxin radioimmunoassay system using Bolton and Hunter reagent was characterized in different biological fluids. In pregnant woman, plasma reveals concentrations from undetectable values to 1,800 pg/ml. Maximal concentrations are found between the 8th and the 13th weeks of pregnancy. These peak values are significantly different from those at other stages of pregnancy. Appreciable relaxin concentrations are detected in gestational corpus luteum extract, and in corpora lutea cyst fluid of pregnant and nonpregnant women. No relaxin was detected in a cyclus corpus luteum extract, in a placental extract, or in an ovarian serous cyst. The presence of immunoreactive relaxin in the nonpregnant woman is reported.


Federal government initiates National Practitioner Data Bank.
The formulation of the data bank will require the exchange of data and merging of information from a number of sources. The development and the implementation of this computerized system will be the work of the UNISYS Corporation in concert with the Bureau of Health Professions' Office of Quality Assurance, a part of the Health Resources and Services Administration, HHS. The assurance of the quality of the data on each nurse--correct, up-to-date, etc.--is the responsibility of the parties reporting to the data bank. In addition, each and every pediatric nurse practitioner will need to become knowledgeable regarding the data base and periodically ascertain that the information regarding himself or herself is correct. As additional information is received on the process by which you can monitor the bank's data on you, it will be published.


RF transmit power limit for the barewire loopless catheter antenna.
The safety of the barewire loopless catheter antenna in transmit mode is addressed with respect to radiofrequency (RF) heating. Analytical expressions for electric field and specific absorption rate (SAR) distributions surrounding the antenna are postulated and experimentally verified. Limiting RF transmit power to 40-70 mW time-averaged power, depending on the specific antenna design, will ensure that the current regulatory guideline of SAR of 8 W/kg in any gram of tissue is not exceeded. These limits can act as guidelines for the design of RF pulses for use with this device. Further study is required to examine the safety of the antenna in receive mode.


Diaphragm dysfunction after cardiac surgery: a global approach.
Diaphragm ultrasound is a noninvasive technique that can be used to assess diaphragm function. In cardiac surgery, the technique may help physicians during the weaning process, in addition with echocardiography after surgery.


Fogarty balloon catheter ablation of neonatal posterior urethral valves.
We describe a technique to ablate posterior urethral valves with a Fogarty balloon catheter. This technique has been used for 14 years in 10 cases with a good result in 9. Fogarty balloon catheter ablation of posterior urethral valves would seem to be particularly applicable to the small neonate with a vulnerable anterior urethra.


Developing a consolidated research framework for clinical allied health professionals practising in the UK.
Allied Health Professionals (AHPs) form a significant part of the healthcare workforce and have great potential to improve services through research and research-informed practice. However, there is a lack of tradition in research embedded in practice in these professional groups. Barriers include clinical caseload pressures, a lack of sustainable training and consequent lack of confidence in practitioners. Practice managers are ill-equipped to monitor and guide staff research development. The modern healthcare system is a multi-disciplinary environment focused on the needs of the patient. A common framework across all AHP disciplines, offering equality in research knowledge and skills and shared language, might be helpful in planning and developing clinical career pathways. Our aim is to develop a consolidated research framework to help AHPs to plan and guide research activity throughout their career. The study was conducted in three phases. Phase one identified existing AHP research frameworks (AHPRF) through expert consultations and literature searches. Phase two involved framework analysis of the AHPRFs to develop a single consolidated framework. Phase three included a workshop with experts to validate and adapt the framework for practice. Nineteen AHPRFs were identified. A consolidated framework was shaped by analysis of the AHPRFs resulting in a consolidated framework of eight sections, each containing a series of statements. Each section relates to an analytic theme within the framework analysis, and the statements were based on sub-categories of themes. The final framework was further shaped by the phase three workshop into a set of 'stem' statements that can be adapted to reflect different levels of expertise and the inclusion of a set of guiding principles developed through expert consultation. The consolidated framework was entitled 'Shaping Better Practice Through Research: A Practitioner Framework' by stakeholders, thus emphasising its ambition to embed research activity into practice. It instigates a new perspective within AHP research by offering practitioners and managers a tool that can be applied across public, private, and voluntary settings for AHPs in all disciplines. Its ambition is to develop capacity in the AHPs that can undertake research to improve services and the health of service users.


Subthreshold Conduction of Disordered ZnO-Based Thin-Film Transistors.
This study presents the disorderedness effects on the subthreshold characteristics of atomically deposited ZnO thin-film transistors (TFTs). Bottom-gate ZnO TFTs show n-type enhancement-mode transfer characteristics but a gate-voltage-dependent, degradable subthreshold swing. The charge-transport characteristics of the disordered semiconductor TFTs are severely affected by the localized trap states. Thus, we posit that the disorderedness factors, which are the interface trap capacitance and the diffusion coefficient of electrons, would result in the degradation. Considering the factors as gate-dependent power laws, we derive the subthreshold current-voltage relationship for disordered semiconductors. Notably, the gate-dependent disorderedness parameters are successfully deduced and consistent with those obtained by the gm/Ids method, which was for the FinFETs. In addition, temperature-dependent current-voltage analyses reveal that the gate-dependent interface traps limit the subthreshold conduction, leading to the diffusion current. Thus, we conclude that the disorderedness factors of the ZnO films lead to the indefinable subthreshold swing of the ZnO TFTs.


Characteristics and health care costs in patients with a diagnostic imaging for low back pain in Switzerland.
Low back pain (LBP) is one of the most common musculoskeletal disorders worldwide and a frequent cause for health care utilization with a high economic burden. A large proportion of diagnostic imaging in patients with LBP is inappropriate and can cause more harm than good, which in turn can lead to higher health care costs. The aim of this study was to determine characteristics and health care costs for patients with a diagnostic imaging for LBP in Switzerland. Groupe Mutuel, one of the biggest health care insurance companies in Switzerland and covering approximately 12% of the population, provided data for this analysis. Patients were identified by diagnostic imaging for the lumbar spine in 2016 or 2017. The study period was 2015-2019, that is one year before and two years after the year of imaging. Regression analysis models were used to identify patient variables associated with higher health care costs. A total of 75,296 patients (57% female, mean age: 54.5 years) were included into the study. Magnetic resonance imaging was the most commonly used diagnostic method (44.3%). Patients generated annual mean health care costs of 518,488,470 CHF (466,639,621 Euro) in the whole observation period; 640 million CHF (576 million Euro) in the index year. Overall, costs for LBP patients were 72% higher compared with the costs of no LBP patients. Our findings confirm the economic burden of LBP and highlight the importance of ongoing efforts to improve prevention, diagnostics and patient care in patients with LBP.


Classification of aneurysms of the internal carotid system.
Microsurgery has improved the treatment of cerebral aneurysms techically and by more detailed knowledge of the topographic relations, the variations, and the anomalies of the involved arteries. A personal study of 450 aneurysms formed the basis of a modified and more detailed classification of aneurysms of the carotid system. It was confirmed that aneurysms originate at the junctions of arteries, and generally project according to the course of the vessel involved. The origins and projections aneurysms and their different sites were analyzed with the aid of angiography, angiotomography, magnification angiography, operative drawings, photographs, and films, which permitted the establishment of a special classification for every particular form. Preoperative knowledge of the types of aneurysms facilitates the surgical procedures and results in lowered morbidity.


A proposed mechanism for the Berecek phenomenon with implications for cardiovascular reprogramming.
Berecek et al reported in the 1990s that when spontaneously hypertensive rat (SHR) mating pairs were treated with captopril and the resulting pups were continued on the drug for 2 months followed by drug discontinuation, the pups did not develop full blown hypertension, and the cardiovascular structural changes associated with hypertension in SHR were mitigated. The offspring of the pups also displayed diminished hypertension and structural changes, suggesting that the drug therapy produced a heritable amelioration of the SHR phenotype. This observation is reviewed. The link between cellular renin angiotensin systems and epigenetic histone modification is explored, and a mechanism responsible for the observation is proposed. In any case, the observations of Berecek are sufficiently intriguing and biologically important to merit re-exploration and definitive explanation. Equally important is determining the role of renin angiotensin systems in epigenetic modification.


Major histocompatibility complex class II polymorphic variants are associated with asthma predisposition in the Punjabi population of Lahore, Pakistan.
Various genome wide association studies have manifested that Major Histocompatibility Complex (MHC) region on chromosome 6p21 houses many potential candidate genes for asthma. This Case-Control association study was planned to determine the association of 10 Single Nucleotide Polymorphisms (SNPs), residing within and around MHC genes' region on chromosome 6p21, with Asthma in Punjabi population of Lahore, Pakistan. A total of 161 subjects, 61 physician-diagnosed asthma patients and 100 age-matched healthy controls, were recruited from Lahore, a city in Punjab. Ten single nucleotide polymorphisms (SNPs) (rs9378249, rs2070600, rs404860, rs6689, rs1049124, rs1063355, rs1049225, rs1049219, rs7773955 and rs928976) located within or near AGER, NOTCH and HLA genes in MHC region, were genotyped in both patients and controls using single base extension reaction and capillary electrophoresis-based genetic analyser. Statistical models were applied using SHEsis Plus. Results were adjusted for various cofactors (age, gender and environment) and by applying multiple corrections. Haplotype and linkage disequilibrium analyses were performed on Haploview software v4.1. Three of the studied SNPs rs1049124, rs1049219 and rs7773955 show independent significant association with asthma under allelic and genotypic models. Two of the haplotypes, H7 and H13, "CTAATTT" and "CCACTAT", respectively, for rs2070600, rs404860, rs6689, rs1049124, rs1063355, rs1049219 and rs7773955, are found to be significantly associated with the disease. This study reports association of SNP variants residing on HLA-DQB1 and HLA-DQA2 genes and haplotypes H7 and H13 on genomic region 6p21 with Asthma in the Punjabi population of Lahore, Pakistan.


A Systematic Review of the Effect of Cognitive Strategies on Strength Performance.
Researchers have tested the beliefs of sportspeople and sports medicine specialists that cognitive strategies influence strength performance. Few investigators have synthesised the literature. The specific objectives were to review evidence regarding (a) the cognitive strategy-strength performance relationship; (b) participant skill level as a moderator; and (c) cognitive, motivational, biomechanical/physiological, and emotional mediators. Studies were sourced via electronic databases, reference lists of retrieved articles, and manual searches of relevant journals. Studies had to be randomised or counterbalanced experiments with a control group or condition, repeated measures, and a quality control score above 0.5 (out of 1). Cognitive strategies included goal setting, imagery, self-talk, preparatory arousal, and free choice. Dependent variables included maximal strength, local muscular endurance, or muscular power. Globally, cognitive strategies were reliability associated with increased strength performance (results ranged from 61 to 65 %). Results were mixed when examining the effects of specific strategies on particular dependent variables, although no intervention had an overall negative influence. Indeterminate relationships emerged regarding hypothesised mediators (except cognitive variables) and participant skill level as a moderator. Although cognitive strategies influence strength performance, there are knowledge gaps regarding specific types of strength, especially muscular power. Cognitive variables, such as concentration, show promise as possible mediators.


Impaired long-term potentiation in obese zucker rats: possible involvement of presynaptic mechanism.
Electrophysiological investigation of basal synaptic transmission and synaptic plasticity in the CA1 region of the hippocampus was carried out in anesthetized obese Zucker rats (OZR). Comparison of the input/output curves of basal field excitatory postsynaptic potential indicates that these are similar in both the OZR and its lean counterpart suggesting that basal synaptic transmission is intact in the OZR. However, high frequency stimulation evokes long-term potentiation (LTP) in the lean rat but not in the OZR. Since post-tetanic potentiation and paired pulse facilitation, forms of short-term potentiation of presynaptic origin, are also severely impaired in the OZR, the results imply that impairment of CA1 hippocampal LTP in these obese rats may be due, in part, to impaired presynaptic function. The results emphasize the potential deleterious effect of obesity on learning and memory functions of the CNS.


Cytochrome P450 aromatase in testis and epididymis of male rhesus monkeys.
To understand the role of estrogen in testicular and epididymal function of rhesus monkeys, we measured steroids in the spermatic and peripheral venus circulation and aromatase activity and its mRNA in testis and epididymis. Testosterone, estradiol-17beta, and estrone, but not androstenedione, were elevated in the spermatic vein serum compared to the peripheral circulation. Aromatase activity in testis and in caput epididymis (259+/-16 [SEM] vs 274+/-47 fmol of 3H2O/mg of protein/h [n = 10], respectively) was significantly higher (p < 0.01) than in corpus and cauda (124+/-28 and 113+/-33 fmol of 3H2O/mg of protein/h [n = 10], respectively). In the ribonuclease protection assay, two P450arom mRNA transcripts were identified in testis and epididymis. One corresponded with the aromatase full-length transcript and the other was a truncated isoform. The latter was significantly more abundant than the former (p < 0.01). Our results demonstrate that the monkey testis and, to a lesser extent, the epididymis can aromatize androgens. However, in the epididymis, like in some areas of the brain, there was a discrepancy between the aromatase activity and the mRNA. The fact that P450arom mRNA and aromatase activity do not correlate in the epididymis may indicate that aromatase activity is not strictly regulated at the level of RNA expression and that other mechanisms for this regulation should be considered.


Single-cell immune profiling reveals broad anti-inflammation response in bipolar disorder patients with quetiapine and valproate treatment.
Bipolar disorder (BD) is a common mental disorder characterized by manic and depressive episodes. Mood disorders have been associated with immune dysfunction. The combination of quetiapine and valproate has shown positive effects in treating BD, but the impact on immune dynamics remains less understood. Using single-cell RNA sequencing, we observed that B cells exhibited downregulation of inflammation-related genes, while pro-inflammatory mast and eosinophil cells decreased following treatment. Ribosomal peptide production genes were found to be reduced in both B and T cells after treatment. Additionally, our findings suggest that the combined therapy effectively alleviates inflammation by reducing myloid-mediated immune signaling pathways. This study provides valuable insights into the immune atlas and uncovers a potential mechanism for immune disorder alleviation in patients with BD treated with quetiapine and valproate.


The initial evaluation in maxillofacial trauma.
Evaluation in maxillofacial trauma is primarily an extension of the art of the physical examination, with inspection, palpation, and evaluation of loss of normal function as the primary requisites. X-ray evaluation is critical, and best results are usually obtained by taking films as soon following the injury as possible, before opacification of the sinus with blood, swelling, or hematoma obscures critical bone landmarks. Primary reduction and surgical management of these fractures can usually be delayed for a reasonable period; however, the most accurate findings on both physical examination and x-ray studies are those obtained as soon as possible after the injury.


Mutational analysis of 3' splice site selection during trans-splicing.
trans-Splicing is essential for mRNA maturation in trypanosomatids. A conserved AG dinucleotide serves as the 3' splice acceptor site, and analysis of native processing sites suggests that selection of this site is determined according to a 5'-3' scanning model. A series of stable gene replacement lines were generated that carried point mutations at or near the 3' splice site within the intergenic region separating CUB2.65, the calmodulin-ubiquitin associated gene, and FUS1, the ubiquitin fusion gene of Trypanosoma cruzi. In one stable line, the elimination of the native 3' splice acceptor site led to the accumulation of Y-branched splicing intermediates, which served as templates for mapping the first trans-splicing branch points in T. cruzi. In other lines, point mutations shifted the position of the first consensus AG dinucleotide either upstream or downstream of the wild-type 3' splice acceptor site in this intergenic region. Consistent with the scanning model, the first AG dinucleotide downstream of the branch points was used as the predominant 3' splice acceptor site. In all of the stable lines, the point mutations affected splicing efficiency in this region.


E-PASS score as a useful predictor of postoperative complications and mortality after colorectal surgery in elderly patients.
The aim of this study was to clarify whether a surgical-specific risk scoring system estimating the physiologic ability and surgical stress (E-PASS) score was useful for prediction of postoperative morbidity and mortality. The E-PASS score consists of the preoperative risk score (PRS), surgical stress score (SSS), and the comprehensive risk score (CRS). Conventional scoring systems [colorectal physiologic and operative severity score for the enumeration of mortality (CR-POSSUM) and the prognostic nutritional index (PNI)] were also examined. We retrospectively compared these scores in patients with or without postoperative complications. We assessed the relationship between these scores, clinicopathological features and postoperative mortality. Postoperative complications developed in 78 patients (33%). American Society of Anesthesiologists score, performance status, PNI score, PRS, SSS, and CRS were significantly higher in patients with postoperative complications than in those without postoperative complications (p < 0.05). The area under the receiver operating characteristic curve (AUC) was highest for E-PASS [E-PASS (PRS, 0.74; SSS, 0.62; CRS, 0.78), PNI (0.62), CR-POSSUM (PS, 0.57; OSS, 0.52)]. Multivariate logistic analysis identified CRS ≥ 0.2 as a significant determinant of postoperative complications (p < 0.01; hazard ratio, 4.84). Overall survival was significantly better in the CRS < 0.2 group than in the CRS > 0.2 group (p < 0.01). The E-PASS score system was a useful predictor of postoperative complications and mortality, especially in patients with advanced age.


[Immediate and severe epistaxis caused by traumatic rupture of the carotid siphon. Apropos of a case treated by intravascular approach].
The authors report a recent case of massive and immediate epistaxis resulting from a rupture of the internal intracavernous carotid artery caused by closed head injury. The point out the unusualness and the extreme severity of such lesions. The pathogenesis of these epistaxis can be explained by an immediate arterial rupture proceeding from a sphenoidal fracture. The emergency bilateral carotid angiography states precisely the diagnosis and the level of the rupture, allowing in the same time the intravascular treatment by detachable balloon.


Characterization of an apolipoprotein C-III mutant by high-performance liquid chromatography and time-of-flight secondary ion mass spectrometry.
Apolipoprotein (apo) C-III isoforms from a patient with a mutant apo C-III and from controls were isolated to homogeneity by isoelectric focusing and subjected to proteolytic digestion. The peptides obtained were separated by reversed-phase high-performance liquid chromatography, and their molecular masses were determined by time-of-flight secondary ion mass spectrometry. Molecular masses of peptides derived from apo C-III0, C-III1 and C-III2 were indistinguishable from control preparations, whereas the mutant apo C-III contained a COOH-terminal, carbohydrate-containing peptide with an abnormal retention time in high-performance liquid chromatography and a molecular mass higher by 291 daltons owing to oversialation at position 74 of the amino acid sequence (apo C-III3).


Effects of mixed carriers on diatomite supported nano-TiO2.
In this study, calcium carbonate, sepiolite, and commonly used diatomite (DE) carriers were mixed to prepare calcium carbonate or sepiolite mixed DE/nano-titanium dioxide (TiO2). The analyses of X-ray diffraction and scanning electron microscope confirmed that the particle size of nano-TiO2 was about 20-24 nm in DE/nano-TiO2, and the particles were relatively uniform. When (calcium carbonate and sepiolite + DE)/nano-TiO2 was used, the Ti content in the composite remained unchanged, while the particle size of nano-TiO2 increased to a certain extent. Among them, the use of (calcium carbonate + DE)/nano-TiO2 increased the Ti content in the composite material significantly. Therefore, the findings demonstrated the feasibility of nano-TiO2 supported by the mixed carrier.


Surveillance of nosocomial infections in a neurologic intensive care unit.
To assess data on the epidemiology of nosocomial infection (NI) among neurologic intensive care patients. Prospective periodic surveillance study. An 8-bed neurologic intensive care unit (ICU). All those admitted for more than 24 hours during five 3-month periods between January 1999 and March 2003. Standardized surveillance within the German infection surveillance system. Three hundred thirty-eight patients with a total of 2,867 patient-days and a mean length of stay of 8.5 days were enrolled during the 15-month study period. A total of 71 NIs were identified among 52 patients. Urinary tract infections (UTIs) were the most frequent NI (36.6%), followed by pneumonia (29.6%) and bloodstream infections (BSIs) (15.5%). The overall incidence and incidence density of NIs were 21.0 per 100 patients and 24.8 per 1,000 patient-days, respectively. Incidence densities were 9.8 UTIs per 1,000 urinary catheter-days (CI95, 6.4-14.4), 5.6 BSIs per 1,000 central venous catheter-days (CI9s, 2.8-10.0), and 12.8 cases of pneumonia per 1,000 ventilation-days (Cl95, 8.0-19.7). Device-associated UTI and pneumonia rates were in the upper range of national and international reference data for medical ICUs, despite the intensive infection control and prevention program in operation in the hospital. Neurologic intensive care patients have relatively high rates of device-associated nosocomial pneumonia and UTI. For a valid comparison of surveillance data and implementation of targeted prevention strategies, we would strongly recommend provision of national benchmarks for the neurologic ICU setting.