A non-human primate test of abstraction and set shifting: an automated adaptation of the Wisconsin Card Sorting Test.
Functional assessment of the prefrontal cortices in the non-human primate began with the seminal work of Jacobsen in the 1930s. However, despite nearly 70 years of research, the precise nature of the cognitive function of this region remains unclear. One factor that has limited progress in this endeavor has been the lack of behavioral tasks that parallel most closely those used with humans. In the present study, we describe a test for the non-human primate that was adapted from the Wisconsin Card Sorting Task (WCST), perhaps the most widely used test of prefrontal cognitive function in humans. Our adaptation of this task, the Conceptual Set-Shifting Task (CSST), uses learning criteria and stimuli nearly identical to those of the WCST. The CSST requires the animal to initially form a concept by establishing a pattern of responding to a given stimulus class, maintain responding to that stimulus class, and then shift to a different stimulus class when the reward contingency changes. The data presented here establishes baseline performance on the CSST for young adult rhesus monkeys and demonstrates that components of prefrontal cognitive function can be effectively assessed in the non-human primate in a manner that parallels the clinical assessment of humans.


Lipid content and carbon assimilation in Collembola: implications for the use of compound-specific carbon isotope analysis in animal dietary studies.
In an effort to understand the relationships between both the lipid content and delta13C values of Collembola and their diet, isotopically labelled (C3 and C4) bakers' yeasts were cultured and fed to two Collembolan species, Folsomia candida and Proisotoma minuta. The fatty acid composition of Collembola generally reflected that of the diet with the addition of the polyunsaturated components 18:2(n-6), 20:4(n-6) and 20:5(n-3), which appeared to be biosynthesised by the Collembola. Whilst ergosterol was the only sterol detected in the yeast diets, only cholesterol was detected in Collembola, and although the delta13C values of diet and consumer sterols differed by >2 per thousand, the delta13C values indicated that cholesterol was derived entirely from dietary sterol. The bulk delta13C values of Collembola were similar to those of the diets, but fatty acid delta13C values did not necessarily reflect those of the dietary fatty acids, indicating significant de novo biosynthesis of fatty acids within Collembola. Switching the Collembola from C3 to C4 yeast enabled the determination of the rates of incorporation of dietary carbon into Collembolan lipids, and showed that half-lives of the incorporation of dietary carbon varied between 1.5 and 5.8 days at 20 degrees C. Cholesterol exhibited the slowest rate of incorporation in both species, while bulk carbon in F. candida possessed an intermediate rate. These results demonstrate that an understanding of the sources of isotopic fractionation and the role of biochemistry in regulating the delta13C values of individual compounds is important in the application of compound-specific isotopic analysis to the study of animal trophic activities.


Effect of viscoelastic deformation of soft tissue on stresses in the structures under complete denture.
The time dependency of stress distribution in the supporting structures under dentures was simulated, under three loading conditions, by visco-elastic finite element stress analysis. In this simulation, viscoelastic material, was used as a model for soft tissue. The results indicate that the viscous flow of soft tissue and the loading position are factors determining stress intensity in the supporting structures under the denture. The stress intensity in the supporting structures was lowered when the occlusal force shifted towards the palatal side. Simulated results support Pound's lingualized occlusion theory.


[Photographing to advance, the use of photography in psychotherapy].
The practice of the clinical psychologist in child psychiatry can be a perilous task. His balance, as precarious as it may be, lies in listening to and observing the patient, but also in the use of precious tools of which therapeutic mediations are a part. They allow to experiment a sensory-motor anchorage and bring a multidimensional vision necessary to the comprehension of the subject and his suffering. By creating an intermediary space between the I and the You, the outside and the inside, they determine a place where the psychotherapeutic work can take place.


Compliance with infection control standard precautions guidelines: a survey among dental healthcare workers in Hail Region, Saudi Arabia.
The concept of standard precautions (SP) has been a cornerstone of dental infection control (IC) practice. Full adherence with SP guidelines is still a matter of concern in many institutions. The objectives of the present study were to assess and characterise compliance with SP guidelines among dental healthcare workers (DHCWs) and to analyse factors that affect compliance. A regional cross-sectional questionnaire survey among DHCWs in all health facilities was carried out from August to November 2014. A total of 307 returned valid self-report questionnaires with a response rate of 73.1%. Most participants (86.3%) were aware of the SP guidelines, 84.4% received IC training and 88.9% received hepatitis B vaccination. Compliance with SP was found to be high; the majority (90.1%) attained 75% on the compliance scale. In the multivariate logistic regression model, perceived higher institutional commitment as regard IC requirements (odds ratio [OR], 4.34; P <0.001), perceived training as adequate (OR, 3.51; P = 0.003), dentist job (OR, 2.99; P = 0.035) and younger age (OR, 0.59; P = 0.041) were independently predicted as good compliant behaviour. This survey revealed high self-reported compliance with SP guidelines. Institutional factors appear to have an important role. Attention should be paid to dental assistants and private DHCWs.


Early pubertal female rats are more resistant than males to 6-hydroxydopamine neurotoxicity and behavioural deficits: a possible role for trophic factors.
The infusion of 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway in rats is commonly used to produce an animal model of Parkinson's disease (PD). However, most studies use male adult animals only. The present study focused on possible gender differences in vulnerability to 6-OHDA during the early pubertal period when the effects exerted by gonadal steroid hormones are unpronounced. Young Sprague-Dawley rats, 35 days of age, were given a low vs. a higher dose of 6-OHDA in the medial forebrain bundle (MFB). Control rats received equivalent saline infusions. At 14 days post-surgery the rats were evaluated for forelimb akinesia. For the higher dose of 6-OHDA the female rats were less impaired than males in making adjustment steps in response to a weight shift and in a vibrissae-evoked forelimb placing test. Tyrosine hydroxylase (TH) immunoreactivity was significantly higher for the female rats. Early gender differences in cell survival factors and/or other promoters of neuroplasticity may have contributed to the beneficial outcome in the females. For example, NGF was found to be higher in the female rats following administration of DA neurotoxin. It is unclear whether gonadal steroids are involved, and if so, whether female hormones are protective or whether male hormones are prodegenerative. Determining the mechanisms for the improved outcome in the young female rats may lead to potential treatment strategies in PD.


Redox-directed identification of toxic transformation products during ozonation of aromatics.
The toxicity assessment of transformation products (TPs) formed in oxidative water treatment is crucial but challenging because of their low concentration, structural diversity, and mixture complexity. Here, this study developed a novel redox-directed approach for identification of toxic TPs without the individual toxicity and concentration information. This approach based on sodium borohydride reduction comprised an integrated process of toxicological evaluation, fluorescence excitation-emission matrix characterization, high-resolution mass spectrometry detection, followed by ecological toxicity assessment of identified TPs. The redox-directed identification of primary causative toxicants was experimentally tested for the increased nonspecific toxicity observations in the ozonated effluents of model aromatics. Reduction reaction caused a remarkable decrease in toxicity and increase in fluorescence intensity, obtaining a good linear relation between them. More than ten monomeric or dimeric p-benzoquinone (p-BQ) TPs were identified in the ozonated effluents. The occurrence of the p-BQ TPs was further verified through parallel sodium sulfite reduction and actual wastewater ozonation experiments. In vitro bioassays of luminescent bacteria, as well as in silico genotoxicity and cytotoxicity predictions, indicate that the toxicity of p-BQ TPs is significantly higher than that of their precursors and other TPs. These together demonstrated that the identified p-BQ TPs are primary toxicity contributors. The redox-directed approach facilitated the revelation of primary toxicity contribution, illustrating emerging p-BQs are a concern for aquatic ecosystem safety in the oxidative treatment of aromatics-contaminated wastewater.


Early and multifocal tumors in breast, salivary, harderian and epididymal tissues developed in MMTY-Neu transgenic mice.
Transgenic mice carrying various oncogenes driven by mammary gland specific enhancers develop mammary tumors usually arising in a stochastic way. The only exception is a mouse lineage (TG.NF) carrying an activated rat Neu oncogene driven by the murine mammary tumor virus long terminal repeat (MMTV-LTR) that gave rise to rapid and multifocal mammary tumors interpreted as a result of a single-step neoplastic transformation. The effect of the oncogene appeared to be specific for breast tissue, since salivary and Harderian glands as well as epididymis expressed high levels of Neu but only developed hyperplasia (Muller et al., Cell, (1988) 54, p. 105). Here we describe a transgenic mouse lineage for the MMTV-Neu, analysed up to third generation. Multifocal tumors involving mammary glands arose very rapidly in all females independently from pregnancy and in some males. Moreover, multifocal neoplasias occurred also in salivary and Harderian glands and in the epididymis at a very high rate. These data demonstrate that the Neu oncogene can induce tumors in all the tissues where it is expressed at high levels.


[Changes of photoreceptor layer on spectral domain optical coherence tomography in idiopathic macular hole after vitreous surgery combined with air tamponade].
To evaluate the tamponade effect of sterilized air in vitrectomy for idiopathic macular hole (IMH) as well as changes of photoreceptor layer after surgery. Forty-five eyes of 45 consecutive cases underwent vitrectomy and air tamponade. Surgical outcomes were retrospectively analyzed, consisting of logarithm of the minimal angle of resolution (logMAR) and SD-OCT findings including the size of IMH and the photoreceptor layer defect. Preoperatively, mean BCVA was 0.08 (range, 0.4 to HM), mean hole diameter was 827.4 µm (range, 204 to 1616 µm), and mean diameter of photoreceptor layer defect was 1988.9 µm (range, 792 to 3444 µm). The primary closure rate was 75.6%. One month after surgery, mean BCVA was 0.13 (range, 0.5 to LP), and mean diameter of photoreceptor layer defect was 1285.1 µm (range, 166 to 2553 µm), both presenting a significant decrease. Preoperative hole diameter and postoperative diameter of photoreceptor layer defect were statistically significantly correlated with postoperative BCVA (r = 0.526, 0.628; P < 0.05). Vitrectomy plus air tamponade is safe and effective for the treatment of IMH, and the time for face-down positioning is obviously shortened. Preoperative hole diameter and postoperative diameter of photoreceptor layer defect are major predictive factors of visual acuity.


Melanocytes and melanosis of the oesophagus in Japanese subjects--analysis of factors effecting their increase.
Normal oesophagus specimens taken from 65 autopsy cases and surgical specimens from 127 oesophageal carcinoma cases were examined histopathologically to determine melanocyte incidence and distribution. Melanocytes were found in the epithelio-stromal junction in 7.7% of normal oesophagus specimens examined at autopsy, and in 29.9% of surgical cases with oesophageal carcinoma. Positive specimens in the latter groups, especially from pre-operatively irradiated individuals, showed a more remarkable increase of melanocytes than was evident in any of the normal oesophageal samples. There were no significant differences in incidence between males and females, or between age groups. In cases where the cancer invaded into deeper stroma, the melanocytes were mainly observed in the normal epithelium around the carcinomas. Epithelial and stromal elements of the melanotic mucosa commonly showed hyperplastic changes such as acanthosis or basal cell hyperplasia, and chronic oesophagitis. Melanocytes were observed most commonly in the lower part of the oesophagus, the site where malignant melanoma of the oesophagus, most often originates. These results strongly suggest that the melanocyte increase observed in areas of hyperplastic epithelium and chronic oesophagitis may play an important role as a precursor lesion for malignant melanoma in the oesophagus.


[Neuroleptic treatment by the established psychiatrist. A report of experiences].
Contrary to in-patient psychiatric care, quality assurance in the area of psychiatrists in outpatient practice is hardly in use. Neuroleptic therapy regarding the following quality criteria was examined for 6 months in an outpatient psychiatric practice: choice of neuroleptics, dosage and combination of additional psychopharmacological medications. 13 different neuroleptics were prescribed to 147 schizophrenic patients, most frequently haloperidol and clozapin. 31% of these patients (n = 147) fell below the dosage recommendations for maintenance therapy. The most frequent psychopharmacological combinations were the combination of two neuroleptics (30%), the combination with lithium or carbamazepin (28%) and the combination with antidepressants (23%). Standardised treatment suggestions as guidelines are valuable for psychiatrists in an outpatients setting. In some cases it is necessary to develop individual treatment strategies that vary from the usual treatment standards.


In the shadow of National Socialism: Early emigration and suicide of the oral pathologist Rudolf Kronfeld (1901-1940).
The physician Rudolf Kronfeld (1901-1940) is undoubtedly one of the pioneering and most influential representatives of modern histopathology and oral pathology. Already at a young age he became a protagonist of the renowned, internationally leading "Vienna School". Kronfeld's outstanding professional significance stands in a peculiar contrast to the research situation to date: His curriculum vitae, but also his family background - and here in particular the fate of his family members in the Third Reich - have received little attention so far. Thus, the present study attempts to shed light on Kronfeld's life and work and, in particular, the complex implications of his Jewish background. It is based on archival sources and a systematic re-analysis of the relevant specialist literature. The analysis demonstrates that Kronfeld's early emigration was driven in part by the anti-Semitism that was tangible in Vienna in the 1920s. The last years of his life were considerably burdened by a serious illness and by repressive experiences which his Jewish family members and companions underwent after the "Anschluss" of Austria into Nazi Germany. Both essential events presumably contributed significantly to Kronfeld's sudden suicide in 1940, at the height of his professional success.


Nitric oxide blocks the cell cycle of mouse macrophage-like cells in the early G2+M phase.
The effects of nitric oxide produced by macrophage-like cells (Mm1) on the cell cycle were investigated. Mm1 cells lost proliferative activity in the presence of interleukin-6 (IL-6) and a subpopulation accumulated in the G2+M phase. This level increased in proportion to the incubation time. The DNA content of the cells was slightly lower than that of Mm1 cells treated with vinblastine or demecolcine, drugs which block the cell cycle in the M phase. The peak of the early G2+M phase was reduced by treatment with NG-mono-methyl-L-arginine. However, after treatment with exogenous nitric oxide or sodium nitroprusside, the G0/G1 phase increased, but the early-G2+M and the S phase decreased. The flow cytometry pattern in IL-6-treated Mm1 was the same as that of cytochalasin B-treated Mm1. These data suggest that endogenous nitric oxide affects the microfilament system of IL-6-treated Mm1 cells and blocks the cell cycle in the early G2+M phase.


A quantitative approach for Cd, Cu, Fe and Mn through laser ablation imaging for evaluating the translocation and accumulation of metals in sunflower seeds.
The uptake and accumulation of Cd in sunflower seeds represents an important pathway for imputing potentially toxic metals into human and animal food. In this way, bioimaging of Cd and micronutrients (Cu, Fe and Mn) in the seeds of sunflower grown in soil contaminated with Cd are performed. For this task, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is used in quantitative approach, considering four groups: precursor, control, Cd-low (50mg) and Cd-high (700mg). For attaining our proposals, ICP-MS (nebulizer and auxiliary flow rates and radiofrequency power) and LA (laser intensity, frequency and spot size) parameters were optimized, and the analytical signal improved to 197%, 217%, 232%, and 283%, for 57Fe, 112Cd, 55Mn and 63Cu, respectively. The accuracy of proposed method using LA-ICP-MS is evaluated comparing the CRM results (Tomato leaves, NIST SRM 1573a). No difference is found at 95% confidence level. Regarding Cd accumulation in sunflower seeds, the results indicated that cadmium is translocated to seeds, and the cotyledons showed the highest concentration (Cd-high group), ranging from 10 to 20µgg-1. Considering both total concentration and the distribution in the seeds, Cd uptake is responsible to the homeostasis misbalance of micronutrients, which play an essential role in the sunflower metabolism. Such results highlight the importance of bioimaging evaluation, in the translocation and accumulation of metals, contributing to expand the information available of this culture.


Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service.
Several studies have demonstrated the cost-effectiveness of genetic testing for surveillance and treatment of carriers of germline pathogenic variants associated with hereditary breast/ovarian cancer syndrome (HBOC). In Brazil, seventy percent of the population is assisted by the public Unified Health System (SUS), where genetic testing is still unavailable. And few studies were performed regarding the prevalence of HBOC pathogenic variants in this context. Here, we estimated the prevalence of germline pathogenic variants in BRCA1, BRCA2 and TP53 genes in Brazilian patients suspected of HBOC and referred to public healthcare service. Predictive power of risk prediction models for detecting mutation carriers was also evaluated. We found that 41 out of 257 tested patients (15.9%) were carriers of pathogenic variants in the analyzed genes. Most frequent pathogenic variant was the founder Brazilian mutation TP53 c.1010G > A (p.Arg337His), adding to the accumulated evidence that supports inclusion of TP53 in routine testing of Brazilian HBOC patients. Surprisingly, BRCA1 c.5266dupC (p.Gln1756fs), a frequently reported pathogenic variant in Brazilian HBOC patients, was not observed. Regarding the use of predictive models, we found that familial history of cancer might be used to improve selection or prioritization of patients for genetic testing, especially in a context of limited resources.


High In-Vitro Antitumour Activity of Triphenyltin Coumarin 3-Carboxylate and its Coordination Complexes With Monodentate Oxygen Donor Ligands Against the Epstein Barr Virus (EBV)-DNA Positive Raji and the P-388 Murine Leukaemia Cell Lines, and Evidence for the Suppression by Organotin of the Early Antigen Complex in the EBV Lytic Cycle.
Triphenyltin coumarin-3-carboxylate and its coordination complexes with ethanol, triphenylphosphine oxide, triphenylarsine oxide, diphenylcyclopropenone and quinoline N-oxide exhibited high in vitro cytotoxicity (LC(50) values in the range 0.25-3.4 mug/mL) when tested against EBV-DNA positive Raji cells and P-388 leukaemia cells, compared to the standard drug 5-Fluorouracil, which showed LC(50) values of 11 and >50 mug/mL, respectively, against these cells. Additional tests performed on the Raji cells incubated with the quinoline N-oxide complex in the presence of the tumour promoters, TPA and sodium butyrate, revealed that the diffused and restricted protein components of the early antigen complex were suppressed relative to the control containing only the promoters, indicating impaired function of the genes involved as transactivators in the early lytic cycle of the EBV. The failure of the restriction enzymes Eco R1 and Hind III to cleave the extracted DNA from such treated cells in contrast to the control, coupled with the amplification of the BMLF-1 gene by the PCR technique which was realised only with the DNA of the control and not of the treated sample, point to a punitive interaction of the organotin with the nuclear DNA of the Raji cells.


Long-term safety and use-effectiveness of intrauterine devices.
The long-term safety and effectiveness of Lippes Loops, A, C, and D, Dalkon Shields, Saf-T-Coils, and Cu 7-200 intrauterine devices (IUDs) were evaluated on the basis of 670 insertions in 588 women. Ten-year life-table rates for the Lippes Loops C (291 first insertions) and D (213 first insertions) were evaluated. The Loop C was consistently associated with a significantly higher expulsion rate but lower pregnancy rate as compared with the Loop D. Over-all, the removal rates for these two IUDs were similar. The incidence of pelvic infection and abnormal Papanicolaou smears, the time from IUD removal to conception, pregnancy outcome, and the need for any surgery post-IUD insertion were evaluated for all IUDs and all segments of use.


The effect of botulinum toxin B pretreatment to the blood flow in the microvascular anastomosis.
Although multiple factors can lead to free flap failure, vessel-related accidents are the most important. Many methods have been developed (both intraoperative and postoperative) to prevent vessel-related complications. In this article, we study the effects of a "preoperative treatment" using botulinum toxin B that could enhance the velocity and blood flow of vascular pedicles and decrease vascular accidents. Ten Sprague-Dawley rats were pretreated with botulinum toxin type B at the perivascular area of the femoral vessel. Ten other rats were injected with saline as a control group. After 3 days, pedicle diameter and the peak mean frequency of blood in the pedicle were measured using laser Doppler flowmetry, and the peak mean blood velocity was calculated. We performed a "pedicle division and reanastomosis" operation to compare changes in vessel diameter and peak mean blood velocity. Vessel diameter was significantly increased in the botox-pretreated group for both veins and arteries. A comparison of the deep femoral vein and artery blood velocities showed that the peak mean velocity was significantly higher in the botox group. The average increase in blood velocity was significantly larger in the botox group. Botulinum toxin B is helpful by influencing the microvascular environment through an increase in the blood velocity of the pedicle.


Plate removal after ulnar-shortening osteotomy.
Ulnar-shortening osteotomy using plate and screw fixation is a reliable method for treating various wrist disorders. In some patients the plate remains as a source of discomfort even after the osteotomy has healed and the preoperative complaints have resolved. There is not a large body of information to guide the surgeon in the timing of plate removal should it be needed to address persistent forearm complaints caused by prominent hardware. This study investigated the outcome of patients who had removal of the plate because of persistent symptoms after undergoing ulnar-shortening osteotomy once radiographic healing was apparent. A consecutive series of 40 ulnar shaft-shortening osteotomies was performed in which 14 patients requested removal of the plate because of persistent tenderness despite nonsurgical management. There were 12 Rayhack (11 titanium, 1 stainless steel) and 2 Synthes 3.5-mm dynamic compression titanium plates used. Before removal radiographic union was documented by 2 sets of films taken in multiple planes at least 4 weeks apart. The average time to plate removal was 6.6 months. All patients had resolution of the ulnar forearm pain after hardware removal. There were no repeated surgeries and all patients returned to their prior levels of activity or employment. Patients were followed-up for an average of 17 months after plate removal. There was 1 refracture in an osteoporotic patient when she fell down a flight of stairs 7 months after plate removal. When used for fixation after ulnar shaft-shortening for ulnar-sided wrist pain of various causes 3.5-mm compression plates seem to be removable at 6 to 9 months in symptomatic patients with a low risk for refracture when sequential sets of x-rays confirm healing of the osteotomy site according to this small series of patients.


Early supported discharge for older adults admitted to hospital with medical complaints: a protocol for a systematic review.
Early supported discharge (ESD) aims to link acute and community care, allowing hospital inpatients to return home and continue to receive the necessary input from healthcare professionals that they would otherwise receive in hospital. The concept has been researched extensively in the stroke population, showing reduced length of stay for patients and improved functional outcomes. This systematic review aims to explore the totality of evidence for the use of ESD in an older adult population who have been hospitalised with medical complaints. A systematic review of randomised controlled trials and quasi randomised controlled trials will be carried out in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies will be included if they provide an ESD intervention to older adults admitted to hospital for medical complaints compared with continuing inpatient care. MEDLINE, CINAHL, CENTRAL and EMBASE databases will be searched. The primary outcome measure will be length of hospital stay, secondary outcomes will include functional abilities, falls, quality of life, carer and patient satisfaction, unplanned emergency department re-presentation, unscheduled hospital readmission, nursing home admission or mortality. Titles and abstracts of studies will be screened independently by two authors. The Cochrane Risk of Bias Tool will be used independently by two reviewers to assess the methodological quality of the included studies. GRADE will be used to assess the quality of the body of evidence. A pooled meta-analysis will be conducted using RevMan software V.5.4.1, depending on the uniformity of the data. The authors will present the findings of the review to a patient and public involvement stakeholder panel of older people that has been established at the Ageing Research Centre in the University of Limerick. Formal ethical approval is not required for the review as all data collected will be secondary data and will be analysed anonymously. CRD42021223112.


A multilayer affective computing model with evolutionary strategies reflecting decision-makers' preferences in process control.
Many industrial control problems related to multi-objective optimization, such as controller parameters tuning, often require operators to perform multiple-step interactions without considering the changes of decision-makers' affective states and quantitative description of decision-makers' preferences during the interactive decision. Regarding this problem, we developed a multilayer affective computing model (MACM), including three factors: human personality, emotional space, and affective states, to demonstrate the iterative affective computing during the interactions. First, a concise model of affective computing-driven interactive decision-making was built before three submodules involved were described in detail. (1) An affective state recognition method based on facial expressions was presented, providing the basis for obtaining expert affective states during decision-making. (2) An identification method of affective parameters was given, providing an approach to describing personalized affective state-changing rules of different persons. (3) A definition of decision-makers' preferences in interactive decision-making was specified. In addition, a decision-makers' preferences mining method was developed by the MACM and an iterative learning control (ILC) strategy. Thus, we proposed affective computing-driven interactive decision-making method, which provided a simplified approach to converting the interactive decision problems based on decision-makers' preferences to decision issues based on incremental decision vector, along with assisting computers to learn from human experts and perform decision-making automatically in a general sense. Then, two typical process control cases-PI controller tuning for decoupling problem and manipulate vector optimization for batch processes were used to show the correctness and effectiveness of the contributions. Compared with other traditional optimization algorithms without affective state tracking and recognition (fuzzy control, ILC, reinforcement learning, and so on), experimental results indicated that the proposed method could achieve good performance. Finally, this study presented the efficiency and limitations of using this technique for a specific application.


[Special proceedings of a law project concerning "the accusation of dementia": case of Joseph Firmin nicknamed Retif (1794-1799)].
The study of a long neglected bill about the accused in a state of mental alienation debated by the legislative assembly of the french Directoire (1794-1799) following a ruling in the Joseph Firmin case. The parliamentary debate on this bill is of real historical interest, since for the first time after the french Revolution its thirteen sections propose to institute special proceedings in case of mental alienation, midway between the penal code of 1791, which does not contain such provisions and the napoleonic code of 1810, it opens the way for the wellknown section 64 of this later code which sets the rules for over a hundred and eighty years.


PAHs, PCBs, PBDEs and Pesticides in Cold-Pressed Vegetable Oils.
The aim of this study was to investigate levels of polychlorinated biphenyls (marker and dioxin-like congeners), polycyclic aromatic hydrocarbons (EPA 15 + 1), polybrominated diphenyl ethers (14 predominant congeners) and pesticides (74 compounds) in various cold-pressed vegetable oils. Poppy seed oil, rapeseed oil, sesame seed oil, pumpkinseed oil, hempseed oil, linaire oil, borage oil and evening star oil were investigated. Results of this study revealed that concentrations of PCBs, PBDEs and PAHs were low in majority of the investigated samples. However, high concentrations of organophosphorus insecticides were found. Chlorpyrifos methyl and pirimiphos methyl were the pesticide residues most commonly found in the studied oils. Concentration of 15 + 1 EPA PAHs was within the 17.85-37.16 μg kg(-1) range, concentration of (marker) PCBs varied from 127 to 24,882 pg g(-1), dioxin-like TEQ values were below 0.1 pg TEQ g(-1). Concentration of PBDEs was below LOQ in most cases.


In-house medical education: redefining tele-education.
Hip and tech-savvy medical students and junior doctors are likely to find lecture-based professionalism and ethics modules boring. Medical-based television dramas and films, on the other hand, are exciting and topical, and often feature real-life situations, albeit presented with artistic license. Current "hot" television series, such as House, ER, and Grey's Anatomy, feature scenarios which are thought-provoking, not only for the fascinating cases featured, but also for the ethical dilemmas and professionalism issues which present themselves. We discuss the educational merits of the genre of the medical drama and propose to develop an "In-House" Medical Education Initiative, in which an episode of House is shown, and participants encouraged, at the end of the screening, to discuss the following: ethics, professionalism (communications skills, confidentiality, sensitivity, and empathy), history taking and clinical examination, diagnostic steps and mis-steps, and finally learning points (or take-home messages). Television programs, purported to "rot the mind," can actually be put to good use in the teaching of "soft skills" in medicine.


Association between total hip arthroplasty following periacetabular osteotomy and acetabular component overhang.
There is limited understanding of anterior acetabular component overhang, which induces groin pain, in post-periacetabular osteotomy (PAO) hips during conversion to total hip arthroplasty (THA). The aim of the study were to determine the following: (1) the differences in the amount of acetabular component overhang among pre-PAO hips and post-PAO hips in simulating THA; (2) the factors associated with the amount of component overhang in THA following PAO; (3) whether high component placement with elevation of the hip center by 10 mm reduces the amount of component overhang compared to the anatomical component position in THA following PAO. Computer-based simulations of acetabular component implantation were performed using preoperative and postoperative CT data from 30 patients undergoing PAO. Implantation was performed thrice in each patient: in pre-PAO hips (anatomical component position) and post-PAO hips (anatomical and high component position). Component overhang was measured on the axial plane, which passes through the component center. Overhang was greater in post-PAO hips [mean (SD) overhang: 5.2 (2.9) mm, pre-PAO hips: 10.2 (4.6) mm, post-PAO hips-mean difference, 5.0 mm; p < 0.001]. A smaller distance between the pubic osteotomy and the acetabulum, and greater overhang in pre-PAO hips was independent factors associated with increased overhang in post-PAO hips. Overhang was smaller with the high component position than with the anatomical component position in post-PAO hips [mean (SD) overhang-3.5 mm (2.9) with high component position among post-PAO hips; mean difference, 6.6 mm; p < 0.001). Ten post-PAO hips with the anatomical component position had overhang of at least 12 mm (the likely threshold for groin pain). Of these, 9 hips had reduced overhang (< 12 mm) with the high component position. Acetabular component overhang was more severe in THA following PAO than in THA without prior PAO. Pubic osteotomy should be performed closer to the acetabular rim to prevent severe overhang in potential THA conversion cases. A high component position decreased the risk of severe overhang.


Neuropsychological syndrome in a patient with episodic howling and violent motor behaviour.
A patient with atypical temporal lobe seizures involving violent behavior was found to exhibit the neuropsychological syndrome described by Luria (1966, 1976) as pathognomonic of lesions in the depths of the left temporal lobe. This syndrome, mainly an audioverbal memory defect with relatively intact phonemic hearing, was evident in spite of an intact intellect.


Diagnostic hierarchy of radiological features in soft tissue tumours and proposition of a simple diagnostic algorithm to estimate malignant potential of an unknown mass.
To quantify the diagnostic utility of imaging features in soft tissue masses (STMs) and to provide a ranked list of predictors for malignancy. Imaging features in 260 cases of STMs with verified histology were assessed. Diagnostic properties including sensitivity, specificity, positive and negative predictive values, likelihood/odds ratios (OR) and normalized variance (NV) via random forest analysis were calculated. The diagnostic utility of an 8-item checklist consisting of the highest-ranked features was evaluated through a receiver-operating-characteristics (ROC) curve. The most predictive features (NV/OR in parentheses) were heterogeneous contrast-enhancement in ultrasound (297.9/15.1) and MRI (197.3/11.9), lesion roundness (209.8/5.5), diffusion restriction (175.8/9.3), cystic/necrotic intralesional areas (167.1/8.3), higher patient age (159.0/2.6), surrounding oedema (155.4/6.5) and intralesional Doppler hypervascularity (134.4/5.1). A simple 8-item checklist was highly predictive of malignancy in cases with at least 75% positive features (0.90 area under the ROC curve, 87.0% sensitivity, 84.5% specificity, 59.5% positive and 96.1% negative predictive value, 36.5 odds ratio) even in cases with only partial feature availability. Features vary widely in their diagnostic value in STMs; an 8-item checklist based on the eight most decisive features can be a simple tool to assess the likelihood for malignancy in unknown soft tissue masses, even though a stratified approach is certainly still advisable when first confronted with an STM.


The rhombencephalic recess in the rat. A light and electron microscopic study.
The rhombencephalic recess, an ependymal organ, has been studied for the first time by light- and electron microscopy. It is situated mediosagitally on the floor of the rhomboid fossa at the level of the colliculus facialis. The recess and the superimposed tissue are built up by tanycytes, their apices being connected by tight junctions. HRP, injected into the c.s.f., does not penetrate into the intercellular clefts of the recess area. The recess area reveals a certain autonomy regarding its supply with arteries and capillaries. A blood-brain barrier exists, but shows slight leakage in circumscribed areas as a result of intense transendothelial vesicular transport. The organization of the recess area is compared with that of other ependymal organs, especially circumventricular organs.


Effects of inflammatory bowel disease on students' adjustment to college.
Successful adjustment to college is required for academic success. We investigated whether inflammatory bowel disease (IBD) activity affects this adjustment process. We created an online survey that included a Student Adaptation to College Questionnaire (SACQ), a general quality of life survey (SF-12), a disease-specific short IBD quality of life survey (SIBDQ), and disease activity indices. Undergraduate students across the United States were recruited via social media. Surveys were completed by 65 students with Crohn's disease (CD), 28 with ulcerative colitis, and 214 healthy students (controls). Disease-specific quality of life (SIBDQ results) correlated with IBD disease activity (rho = -0.79; P < .0001). High college adjustment scores (SACQ results) were associated with high SIBDQ scores. Students with IBD had lower mean SACQ scores than controls (307 vs 290; P < .0001). There was a modest inverse correlation between CD activity and SACQ (rho = -0.24; P < .04). Disease activity in students with CD was associated strongly with their self-reported ability to keep up with academic work (P < .0089) and confidence in their ability to meet future academic challenges (P < .0015). Students with active IBD reported feeling as if they were not academically successful (P < .018), and students with ulcerative colitis reported irregular class attendance (P < .043). Students with IBD do not adjust to college as well as healthy students. Disease activity affects their adjustment and attitudes about academics-especially among students with CD. Successful adjustment is important for academic success, affecting graduation rates and future economic success. Strategies to increase disease control and provide social and emotional support during college could improve adjustment to college and academic performance, and increase patients' potential.


Vulnerable Child Syndrome and Newborn Screening Carrier Results for Cystic Fibrosis or Sickle Cell.
To measure parental perceptions of child vulnerability, as a precursor to developing a population-scale mechanism to mitigate harm after newborn screening. Participants were parents of infants aged 2-5 months. Parental perceptions of child vulnerability were assessed with an adapted version of the Vulnerable Baby Scale. The scale was included in the script for a larger study of telephone follow-up for 2 newborn blood screening samples (carrier status for cystic fibrosis or sickle cell hemoglobinopathy). A comparison sample was added using a paper survey with well-baby visits to an urban/suburban clinic. Sample sizes consisted of 288 parents in the cystic fibrosis group, 426 in the sickle cell hemoglobinopathy group, and 79 in the clinic comparison group. Parental perceptions of child vulnerability were higher in the sickle cell group than cystic fibrosis group (P < .0001), and both were higher than the clinic comparison group (P < .0001). Parental perceptions of child vulnerability were inversely correlated with parental age (P < .002) and lower health literacy (P < .015, sickle cell hemoglobinopathy group only). Increased parental perceptions of child vulnerability seem to be a bona fide complication of incidental newborn blood screening findings, and healthcare professionals should be alert to the possibility. From a public health perspective, we recommend routine follow-up after incidental findings to mitigate psychosocial harm.


Ventriculo-peritoneal shunt surgery for tuberculous meningitis: A systematic review.
Ventriculo-peritoneal shunt surgery is one of the most commonly performed surgery for the management of tuberculous hydrocephalus. There is decreased clarity on issues regarding the indication as well as timing of cerebrospinal fluid diversion procedures in tuberculous meningitis. We systematically analysed published literature on this subject with an objective to assess the value of cerebrospinal fluid diversion procedures in tuberculous meningitis. A systematic search of literature was performed using PubMed, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) for articles published till August 2016. All original studies, irrespective of their design, enrolling at least 10 patients with tuberculous meningitis and hydrocephalus, and in whom the outcome following ventriculo-peritoneal shunt was described, were included in this review. Data was extracted on a pre-formed data extraction sheet. Primary outcome was defined using Glasgow outcome scale (GOS). Nineteen studies, comprising of 1038 patients, were included in the review. A majority of patients were children. Good outcome (GOS 5 and 4), following ventriculo-peritoneal shunt, was observed in 58.26% of patients; 78.57% of patients in grade I, 65.35% in grade II and 67.97% in grade III achieved a good outcome while only 31.51% in grade IV could achieve a good outcome. On subgroup analysis, 61.08% of HIV-negative patients achieved a good outcome as compared to only 25% of HIV-positive patients. There were 18.03% deaths in the HIV-negative group as compared to 66.67% deaths in the HIV-positive group after shunt surgery. The rate of complications following ventriculo-peritoneal shunt was 22.11%; shunt blockage, leading to shunt revision, was the most common complication. Majority of included studies were clinically and methodologically heterogeneous. Outcome, following ventriculo-peritoneal shunt, depends on the clinical severity of tuberculous meningitis. HIV-infected patients have a worse prognosis when compared with HIV uninfected patients. Compared to children, corresponding data is sparse for adult patients with tuberculous meningitis.


Glucocorticoid control of the development of tryptophan oxygenase in the young rat.
Tryptophan oxygenase activity follows a characteristic developmental pattern in the young rat, being absent until about 2 weeks of life, then attaining adult levels by the 3rd week. We have investigated the factors which control this process and determined that the increase in enzymatic activity results from increased glucocorticoid release between the 14th and 21st days. This conclusion was based on our observation that adrenalectomy completely arrests the development of the enzymatic activity. Twenty-one-day-old animals which were adrenalectomized on the 10th day, and thus possess no demonstrable enzymatic activity, could respond to cortisol treatment with an elevation of tryptophan oxygenase activity. Administration of either cycloheximide or actinomycin D completely inhibited this response, suggesting that both protein synthesis and RNA synthesis were requisite for the development of the enzyme. Immunochemical studies revealed that the enzyme found in the young animal was identical with that extracted from the adult rat; furthermore, the increase in activity observed in the developing rat is the result of increased enzyme protein levels. Direct measurement of the synthetic and degradative rates showed the accumulation of enzyme protein to depend upon increased synthetic activity, and not upon decreased enzyme degradation.


Sulfur-decorated Fe/C composite synthesized from MIL-88A(Fe) for peroxymonosulfate activation towards tetracycline degradation: Multiple active sites and non-radical pathway dominated mechanism.
Peroxymonosulfate (PMS)-mediated advanced oxidation processes gain growing attention in degrading antibiotics (e.g., tetracycline (TC)) in wastewater for their high capacity and relatively low cost, while designing efficient catalysts for PMS activation remains a challenge. In this study, a sulfur-doped Fe/C catalyst (Fe@C-S) synthesized from iron metal-organic frameworks (Fe-MOFs) was developed for PMS activation towards TC removal. Under optimal conditions, the TC removal efficiency of Fe@C-S150/PMS system within 40 min was 91.2%. Meanwhile, the k value for Fe@C-S150/PMS system (0.2038 min-1) was 3.36-fold as high as the S-free Fe@C-based PMS system. Also, Fe@C-S150/PMS system showed high robustness in different water matrices. Further studies found that the TC degradation mechanism was mainly ascribed to the non-radical pathway (1O2 and electron transfer). Fe nanoparticles, S and CO groups on the catalyst all participated in the generation of reactive oxygen species (ROS). Besides, S species could enhance the Fe2+/Fe3+ redox cycle and accelerate the electron transfer process. This work highlights the critical role of S in enhancing the catalytic performance of Fe/C-based catalysts for PMS activation, which would provide meaningful insights into the design of high-performance PMS activators for the sustainable remediation of emerging contaminants-polluted water bodies.


A European Research Agenda for Geriatric Emergency Medicine: a modified Delphi study.
Geriatric Emergency Medicine (GEM) focuses on delivering optimal care to (sub)acutely ill older people. This involves a multidisciplinary approach throughout the whole healthcare chain. However, the underpinning evidence base is weak and it is unclear which research questions have the highest priority. The aim of this study was to provide an inventory and prioritisation of research questions among GEM professionals throughout Europe. A two-stage modified Delphi approach was used. In stage 1, an online survey was administered to various professionals working in GEM both in the Emergency Department (ED) and other healthcare settings throughout Europe to make an inventory of potential research questions. In the processing phase, research questions were screened, categorised, and validated by an expert panel. Subsequently, in stage 2, remaining research questions were ranked based on relevance using a second online survey administered to the same target population, to identify the top 10 prioritised research questions. In response to the first survey, 145 respondents submitted 233 potential research questions. A total of 61 research questions were included in the second stage, which was completed by 176 respondents. The question with the highest priority was: Is implementation of elements of CGA (comprehensive geriatric assessment), such as screening for frailty and geriatric interventions, effective in improving outcomes for older patients in the ED? This study presents a top 10 of high-priority research questions for a European Research Agenda for Geriatric Emergency Medicine. The list of research questions may serve as guidance for researchers, policymakers and funding bodies in prioritising future research projects.


Aminoglycoside neurotoxicity involves NMDA receptor activation.
Previous studies have led to the hypothesis that the ototoxicity produced by aminoglycoside antibiotics involves the excitotoxic activation of cochlear NMDA receptors. If this hypothesis is correct, then these antibiotics should also injure neurons within the brain. Because aminoglycosides do not readily penetrate the blood brain barrier, we examined the effects of the aminoglycoside neomycin following intrastriatal injection. Neomycin (10-250 nmol) produced dose-dependent striatal damage manifested as an increased gliosis as measured by: (1) [3H]PK-11195 binding, (2) staining for the astrocytic marker glial fibrillary acidic protein (GFAP) and (3) staining for OX-6, an MHC class II antigen expressed by microglia and macrophages. Co-injection of subthreshhold doses of NMDA potentiates the striatal damage produced by neomycin (10 nmol). Moreover, neomycin-induced striatal damage is attenuated by a combination of the NMDA antagonists ifenprodil and 5, 7-dichlorokynurenic acid. Intrastriatal administration of compounds structurally related to neomycin, but devoid of modulatory actions at NMDA receptors (paromamine and 2-deoxystreptamine), fail to produce neuronal damage. These data support the hypothesis that aminoglycoside-induced ototoxicity is, in part, an excitotoxic process involving the activation of NMDA receptors. Moreover, aminoglycosides may damage the central nervous system in individuals with compromised blood brain barriers.


Suprachoroidal electrotransfer: a nonviral gene delivery method to transfect the choroid and the retina without detaching the retina.
Photoreceptors and retinal pigment epithelial cells (RPE) targeting remains challenging in ocular gene therapy. Viral gene transfer, the only method having reached clinical evaluation, still raises safety concerns when administered via subretinal injections. We have developed a novel transfection method in the adult rat, called suprachoroidal electrotransfer (ET), combining the administration of nonviral plasmid DNA into the suprachoroidal space with the application of an electrical field. Optimization of injection, electrical parameters and external electrodes geometry using a reporter plasmid, resulted in a large area of transfected tissues. Not only choroidal cells but also RPE, and potentially photoreceptors, were efficiently transduced for at least a month when using a cytomegalovirus (CMV) promoter. No ocular complications were recorded by angiographic, electroretinographic, and histological analyses, demonstrating that under selected conditions the procedure is devoid of side effects on the retina or the vasculature integrity. Moreover, a significant inhibition of laser induced-choroidal neovascularization (CNV) was achieved 15 days after transfection of a soluble vascular endothelial growth factor receptor-1 (sFlt-1)-encoding plasmid. This is the first nonviral gene transfer technique that is efficient for RPE targeting without inducing retinal detachment. This novel minimally invasive nonviral gene therapy method may open new prospects for human retinal therapies.


Genetic variations in tryptophan hydroxylase in suicidal behavior: analysis and meta-analysis.
Neurobiological studies implicate serotonergic dysfunction in suicidal behavior. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in the biosynthesis of serotonin, plays a vital role in serotonin metabolism. Thus, variations in the TPH gene have been regarded as prime candidates in the susceptibility to suicidal behavior. The most widely studied genetic variations in the TPH gene, which are located in intron 7, yielded conflicting results in individual studies on suicide-related behavior. We performed a meta-analysis on a total of 898 patients and 1179 control subjects, in addition to our local association study in consecutively recruited suicide attempters (n=147) and healthy control subjects of German descent (n=326). We observed a nonsignificant higher frequency of the TPH intron 7 A218 allele in our local group. The meta-analysis showed a weak yet highly significant increase in the frequency of the A218 allele (odds ratio [OR]: 1.33; 95% confidence interval [CI]: 1.17-1.50; p=.00002) and an over-representation of A-carriers (OR: 1.48; 95% CI: 1.22-1.79; p=.00005) in Caucasian suicide attempters/victims. Our meta-analysis provides strong evidence for an association of suicide-related behavior with an A218 single-nucleotide polymorphism in the TPH gene in Caucasians. Because this variation do not seem to alter functional properties of the TPH gene or protein, functional variations remain to be identified and subsequently tested for association with suicide-related behavior.


A physical operation of hydrodynamic orientation of an azobenzene supramolecular assembly with light and sound.
Photoisomerizations of a newly designed azobenzene derivative reversibly change its self-assembly in a solution to form twisted supramolecular nanofibers and amorphous aggregates, respectively. When irradiating the sample solution with audible sound, the former assembly exhibits a LD response due to its hydrodynamic orientation, but the latter one is LD silent, in the sound-induced fluid flows.


Relationship of obesity with serum concentrations of leptin, CRP and IL-6 in breast cancer survivors.
Several mechanisms have been proposed to explain the adverse effect of obesity on quality of life among women with breast cancer, including alteration in some inflammatory markers. The aim of this study was to determine the status of serum levels of leptin, IL-6 and CRP in obese, overweight and normal weight breast cancer survivors in order to determine the relationship between inflammatory markers' levels and obesity. This cross-sectional study was done on 75 women with breast cancer, 30 obese, 15 overweight and 30 normal weight patients. Serum leptin, IL-6, CRP, total protein, albumin and lipid profile as well as anthropometric parameters were measured in three groups. Serum leptin levels of obese patients were significantly higher than those of overweight and normal weight patients (P<0.05). Higher serum CRP and lower albumin levels were observed in obese patients in comparison with normal weight patients (P<0.05). HDL-C level was significantly different between overweight and normal weight patients (P<0.05). Significant differences in serum IL-6 levels were not observed between the study groups (P>0.05). Moreover, multiple regression analysis showed that leptin was significantly associated with BMI (P<0.001), while albumin was negatively correlated with BMI (P<0.05). CRP levels were significantly correlated with BMI and waist-to-hip ratio (WHR) (P<0.05). In conclusion, high leptin levels and alteration in acute phase proteins in obese patients may exaggerate the inflammation status. As inflammation has the potential to increase the susceptibility of the patients to metastasis development, it is necessary to decline its rate.


Sperm deoxyribonucleic acid fragmentation assessment in normozoospermic male partners of couples with unexplained recurrent pregnancy loss: a prospective study.
To determine whether sperm DNA integrity in normozoospermic male partners plays a role in idiopathic recurrent pregnancy loss (RPL). Prospective, cohort study. Academic tertiary care center. Group I: 26 male partners of women with unexplained RPL. Group II: 31 normozoospermic males with proven fertility. Semen samples were collected by masturbation after 48-72 hours of abstinence. After liquefaction at room temperature, semen analysis was performed according to World Health Organization standards. Only samples with >20 × 10(6) spermatozoa/mL with at least 50% progressive sperm motility and 30 % normal morphology were selected for the study. DNA fragmentation of the sperm was assessed with TUNEL assay followed by flow cytometric analysis. Sperm DNA fragmentation in both groups. Mean DNA fragmentation (mean ± SD) was significantly more in men with RPL (36.8 ± 5) compared with controls (9.4 ± 2.7). Sperm DNA fragmentation may play a role in unexplained RPL despite normal semen analysis parameters.


Breast cancer knowledge and practices amongst women in Algeria.
The present study aims at investigating how Algerian women feel about Breast Cancer (BC) and Breast Self-Examination (BSE) in terms of knowledge and attitude and to determine the factors associated with performing BSE and its reluctance. We carried out a cross-sectional survey between October 14, 2021 and November 14, 2022, targeting Algerian females aged more than 18 years and living in the country using a self-administered questionnaire. A total of 436 participants were involved in this study among which 41.28% were aged between 21 and 30 years and 34.86% were aged between 31 and 40 years. The average level of correct responses with regard to knowledge about BC was estimated at 51.31%, whereas it was 32.93% concerning knowledge about BC risk factors. Family history was the less reported incriminating factor for developing BC among the asked women (7.34%). Concerning alarming signs of BC, the current study revealed that Algerian women were less knowledgeable about breast dimpling-puckering (44.27%), breast inward traction (50.23%), breast redness (54.13%), and nipple position change (54.13%). In terms of belief in the utility of BSE in the early detection of BC, almost all the participants (97.98%) were convinced of its utility, whereas 96.33% of them showed an interest in learning more about it. In what concerns the early screening tests, approximately, four-fifth of the participant (77.52%) heard about them, while 94.72% believed that its early detection could reduce the disease's severity and mortality. These findings revealed an insufficient level of knowledge concerning BC, especially in regard to its risk factors and some alarming signs as well as a lack of knowledge about BSE and other BC screening tests; hence the necessity of awareness campaigns about this disease that should target categories with the lowest level of knowledge.


Culture-broker and medical decoder: contributions of caregivers in American Indian cancer trajectories.
Caregivers play a special role in the management and control of cancer-related pain. For American Indians with cancer, caregivers can contribute to patient education, medication compliance, and can facilitate communication between the patient and the provider and the patient and the family. To identify the role(s) of caregivers of American Indian cancer survivors. As a part of a large randomized intervention designed to improve barriers to cancer symptom management, 13 focus groups were held among American Indian cancer survivors and their caregivers at Southwest reservations and urban sites. Focus groups, audiotaped and transcribed, used constant comparative methods in the analysis of caregiver dialogues. Caregivers are patient educators and provider culture-brokers and their communication strategies use a combination of cultural and conventional strategies in their care of American Indian cancer patients. Cultural communication styles include "talk stories" (storytelling), group (talking circles), and dialogue to manage cancer pain, educate the patient and community, and to protect the patient from stigma, reduce barriers to care, and provide support to patients and families. Active discussion with providers "re-packaged" the patient's reporting/responses to specific clinical measures (pain measure scores) and identified the need for pain medication and compliance-related issues. Findings are not generalizable to the American Indian population outside of the sites and focus groups from which data were collected. Caregivers are "cultural brokers" who inform providers of the cultural nuances associated with American Indian patient care. However, caregivers voiced that cultural restriction for not discussing illness openly was a sanction and an important barrier.


Preeclampsia and related disorders. Clinical aspects and relevance of endothelin and nitric oxide.
Preeclampsia is a pregnancy-specific disorder believed to result from widespread endothelial dysfunction. Endothelin and NO are two potent vasoactive agents of endothelial origin and, as such, are postulated to play an important role in the pathogenesis of preeclampsia. If these agents are found to be important in preeclampsia, they will most likely exert their effects locally, rather than systemically. Future research on the autocrine and paracrine effects of endothelin and NO may yield important insights into the cause and pathogenesis of this enigmatic disease.


Simultaneous infection with Cryptococcus neoformans and Legionella pneumophila. In vivo expression of common defects in cell-mediated immunity.
We describe 3 patients with simultaneous infection by Cryptococcus neoformans and Legionella pneumophila. Legionnaires' disease (pneumonia) occurred shortly after onset of cryptococcal meningitis in a cardiac transplant patient receiving ciclosporin, a second patient with chronic lymphocytic leukemia and a third patient with Hodgkin's disease and autoimmune hemolytic anemia. Defects in cell-mediated immunity have been identified in patients with hematologic malignancies and in those who have received organ transplants. Clinical and experimental data suggest that the primary host defense mechanism against cryptococcal and Legionella infection involves cell-mediated immunity. Thus, the simultaneous occurrence of cryptococcal and L. pneumophila infection in these 3 patients supports experimental studies which have demonstrated common host defense mechanisms against both pathogens.


Synovial fluid neutrophil gelatinase-associated lipocalin can be used to accurately diagnose prosthetic joint infection.
Neutrophil gelatinase-associated lipocalin (NGAL) in synovial fluid (SF) may have potential diagnostic value for prosthetic joint infection (PJI). This study aimed to study (i) the diagnostic performance of SF-NGAL levels for diagnosing PJI and (ii) the impact of previous antibiotic use on the SF-NGAL levels. Consecutive patients who needed hip or knee revision surgery were included prospectively from January 2017 to September 2018. The patients were divided into the PJI group and the aseptic failure group. An enzyme-linked immunosorbent assay was used to determine the SF-NGAL level. A total of 50 of 78 included patients were diagnosed with PJI. The median SF-NGAL level was 3633 ng/ml (interquartile range [IQR], 1332-10,737) in the PJI group and 26.8 ng/ml (IQR, 12.4-52.5) in the aseptic failure group (P <0.0001). When the SF-NGAL threshold was 263 ng/ml, the area under the curve was 0.98, the sensitivity was 92.9%, and the specificity was 98%. The median level was 5779 ng/ml (IQR, 1425-13,072) in the antibiotic group and 2590 ng/ml (IQR, 932-8970) in the nonantibiotic group (P = 0.1). SF-NGAL level can be used as a diagnostic indicator of PJI. The use of antibiotics before sampling does not affect the SF-NGAL level.


[Advanced research of mTOR and lung carcinoid tumors].
Mammalian target of rapamycin (mTOR), a main protein kinase in the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway, is an important intracellular mediator involved in multiple celluar functions including proliferation, differentiation, apoptosis, tumorigenesis, and angiogenesis. Recently, the high expression of mTOR and mTOR-related kinase have been found in neuroendocrin tumors. Therefore, mTOR pathway represents an attractive target for new anticancer therapies except surgery.


A Comparison of Endoscopic Versus Surgical Creation of a Cystogastrostomy to Drain Pancreatic Pseudocysts and Walled-Off Pancreatic Necrosis in 5500 Patients.
To determine the success, morbidity, and mortality rates of endoscopic and surgical creation of pancreatic cystenterostomies for the drainage of peripancreatic fluid collections, pseudocysts with necrotic debris, and walled-off pancreatic necrosis. Endoscopic methods of cystenterostomy creation to drain pancreatic pseudocysts (with and without necrotic debris) and infected peripancreatic fluid collections are perceived to be less morbid than surgery. Contemporary reports document a very high complication rate with endoscopic methods. A meta-analysis of 5500 patients. Open and laparoscopic surgical techniques to drain chronic pancreatic pseudocysts, infected pancreatic fluid collections, and walled-off pancreatic necrosis are more successful with less morbidity and mortality than endoscopic methods. In regards to a surgical step-up approach to treat chronic infected pancreatic fluid collections or walled-off pancreatic necrosis, surgical creation of a cystenterostomy is more successful with fewer complications than endoscopic methods and should be given priority if less invasive or conservative methods fail.


Sarcoplasmic calcium-binding proteins in Aplysia nerve and muscle cells.
Muscle (body wall, buccal mass, heart) and neural tissue of the marine mollusc Aplysia californica was analysed for calcium-binding proteins using transblot/45Ca overlay, Western blotting and two-dimensional polyacrylamide gel electrophoresis, and several low molecular weight calcium-binding proteins were identified. Our results that Aplysia muscle contains an abundant protein with a M(r) of approximately 20,000 with strong 45Ca(2+)-binding ability and cross-reactivity to antibodies against the sarcoplasmic calcium-binding protein isoform II (SCP II) from Amphioxus. Immunocytochemical studies revealed that isoforms of SCP are distributed in a tissue-specific manner, SCP II-like protein is exclusively present in muscle fibres closely associated with the contractile machinery, whereas the isoform I (SCP I-like protein) is exclusively present in a subset of neurons, suggesting a function in their calcium regulation. In addition, a novel 45Ca(2+)-binding protein of M(r) 43,000, pl 4.7, was found in muscle and in neurons. A third protein of M(r) 40,000, pl 4.8, cross-reacts with anti-parvalbumin and anti-calbindin D-28K antibodies.


Adverse health effects of indoor moulds.
Building associated illnesses - sick building syndrome (SBS) as a common example - are associated with staying in buildings with poor indoor air quality. The importance of indoor fungal growth in this phenomenon continues to be evident, even though no causative relation has been established so far. Indoor humidity is strongly associated with the symptoms of SBS. Fungal metabolites that may induce ill health in susceptible occupants comprise beta-D-glucan, mycotoxins, and volatile organic compounds as known irritants and/or immunomodulators. Indoor toxic fungal metabolites might be located in micromycetal propagules (endometabolites), in (bio-)aerosol, detritus, and house dust (exometabolites) as their particular carriers. It is highly probable that hyphal fragments, dust, and particles able to reach the alveoli have the strongest depository and toxic potential. Most fungal spores are entrapped by the upper respiratory tract and do not reach further than the bronchi because of their size, morphology, and the mode of propagation (such as slime heads and aggreggation). This is why studies of the toxic effects of fungal spores prefer directly applying metabolite mixtures over mimicking real exposure. Chronic low-level exposure to a mixture of fungal toxicants and other indoor stressors may have synergistic effects and lead to severe neuroendocrineimmune changes.


Distribution and ecological risk of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in surface sediments from the Bizerte lagoon, Tunisia.
Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were determined in 18 surface sediment samples collected from Bizerte lagoon, Tunisia. The total concentrations of ten PCBs (∑PCBs) and of four OCPs (∑OCPs) in the sediments from this area ranged from 0.8 to 14.6 ng g(-1) dw (average value, 3.9 ng g(-1) dw) and from 1.1 to 14.0 ng g(-1) dw (average value, 3.3 ng g(-1) dw), respectively. Among the OCPs, the range of concentrations of dichlorodiphenyltrichloroethane and its metabolites (DDTs) and hexachlorobenzene (HCB) were 0.3-11.5 ng g(-1) dw (1.9 ng g(-1) dw) and 0.6-2.5 ng g(-1) dw (1.4 ng g(-1) dw), respectively. Compositional analyses of the POPs indicated that PCB 153, 138 and 180 were the predominant congeners accounting for 60 % of the total PCBs. In addition, p,p'-DDT was found to be the dominant DDTs, demonstrating recent inputs in the environment. Compared with some other regions of the world, the Bizerte lagoon exhibited low levels of PCBs and moderate levels of HCB and DDTs. The high ratios ΣPCBs/ΣDDTs indicated predominant industrial versus agricultural activities in this area. According to the established guidelines for sediment quality, the risk of adverse biological effects from such levels of OCPs and PCBs, as recorded at most of the study sites, was insignificant. However, the higher concentrations in stations S1 and S3 could cause biological damage.


Toxic heavy metals and nutrient concentration in the milk of goat herds in two Iranian industrial and non-industrial zones.
This work aimed to explore the concentration of nickel, manganese, iron, copper, chromium, and lead in the milk of goat herds in the industrial area of Asaluyeh (southern Iran) and the non-industrial area of Kaki. The milk of 16 goat herds (each herd had at least ten goats) was collected in several villages in each area, and at the same time, the drinking water and forage of goats were sampled. The concentration of elements in the samples was determined by ICP-OES. The mean concentrations of chromium, copper, iron, manganese, lead, and nickel in milk samples of the Asaluyeh area were 16.423 ± 0.349, 0.146 ± 0.118, 6.111 ± 0.501, 0.239 ± 0.016, 0.141 ± 0.030, and 1.447 ± 0.101 mg/kg, respectively. Concentrations of heavy metals (except for copper) in the milk of goats in the industrialized area of Asaluyeh were significantly higher than that of Kaki (P < 0.05). Also, the content of heavy metals was significantly correlated with lactose levels (P < 0.05). The hazard index for drinking the goat milk was computed to be 0.444 and 0.386 for the Asaluyeh and Kaki area, respectively, which shows a minimal effect of this exposure pathway.


DBS in restless legs syndrome: a new therapeutic approach?
Restless legs syndrome (RLS) is a sleep disorder characterized by an urge to move legs or arms, with a typical circadian rhythm. RLS can be treated with pharmacological and non-pharmacological therapies. Nevertheless, in some patients RLS can be refractory to all medical and non-medical treatments. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been reported to improve RLS symptoms in Parkinson's disease (PD) patients with RLS. We describe the case of a patient suffering from refractory idiopathic RLS implanted with bilateral GPi DBS. The patient underwent DBS targeting the bilateral GPi. Follow up for three years involved clinical evaluation and polysomnography (PSG). The patient reported subjective improvement, with reduction in the IRLS score. Furthermore, the polysomnography (PSG) showed an objective improvement of polysomnographic parameters, which remained stable during the follow-up. DBS for RLS can be a new therapeutic approach for severe RLS, but further studies are needed.


The effects of p-chlorophenylalanine (PCPA) treatment on the substance P content measured in discrete brain nuclei of normal and neonatally-induced hypothyroid rats.
Neonatal hypothyroidism is known to induce the accumulation of substance P and serotonin in many discrete brain nuclei of the rat. In this work, we have studied the effects of p-chlorophenylalanine (PCPA), a serotonin (5-HT) depleting drug, on the regional distribution of substance P in the brains of neonatally-induced hypothyroid and euthyroid rats. PCPA injections were given 48 and 24 h before sacrifice and the peptide content of discrete brain nuclei, removed by punches of frozen brain slices, was measured by radioimmunoassay. In hypothyroid animals, substance P levels were significantly increased in the n. paraventricularis, n. medialis thalami, n. arcuatus. n. mamillaris medialis, substantia nigra, area ventralis tegmenti, n. interpeduncularis, substantia grisea and n. dorsalis raphes. This hypothyroid-induced accumulation of substance P was completely abolished, and even reversed in some nuclei, by PCPA treatment. Interestingly, in normal rats, following PCPA treatment, the substance P level was increased in n. paraventricularis pars magnocellularis, n. ventromedialis (hypothalami), n. dorsomedialis pars dorsalis (hypothalami), n. amygdaloideus centralis, area ventralis tegmenti, substantia grisea, n. medianus raphes and n. dorsalis raphes. These results lend support to the existence of a physiological relationship between both substance P and serotonergic systems.


Coordinate regulation of the biosynthesis of ATP-citrate lyase and malic enzyme during adipocyte differentiation. Studies on 3T3-L1 cells.
The biosynthesis and degradation of two lipogenic enzymes were studied during the differentiation of 3T3-L1 preadipocytes into adipocytes. The activity and mass of malic enzyme, rose by an order of magnitude during adipocyte development and the enzyme accounted for 0.3% of the cytosol protein in mature fat cells. Similarly, the activity and amount of ATP-citrate lyase increased approximately 7-fold during the adipose conversion. The relative rates of synthesis of the two enzymes were less than or equal to 0.02% in preadipocytes, but increased sharply as the cells began to differentiate. Maximal steady state rates of malic enzyme and ATP-citrate lyase synthesis in 3T3-L1 adipocytes were 13- and 8-fold higher, respectively, than the basal rates in preadipocytes. In contrast, the half-lives of malic enzyme (67 h) and ATP-citrate lyase (47 h) were not altered during adipocyte development. Thus, accelerated rates of enzyme synthesis account for the differentiation-dependent accumulation of the two lipogenic enzymes. Increased rates of malic enzyme, ATP-citrate lyase, and fatty acid synthetase biosynthesis are expressed in a highly coordinated manner during adipocyte differentiation and are associated with parallel elevations in the levels of translatable mRNAs for these enzymes.


Augmentation of natural cytotoxicity by leucine enkephalin in cultured peripheral blood mononuclear cells from patients infected with human immunodeficiency virus.
Natural Killer (NK) activity of lymphocytes from acquired immunodeficiency syndrome (AIDS) patients is frequently below normal and declines as disease progresses. We studied the potential of leucine enkephalin (leu-enkephalin) to restore this immune parameter by incubating nylon wool nonadherent mononuclear cells from 14 patients in the presence or absence of leu-enkephalin, and measuring NK cytolysis in a standard 51Cr release assay. The NK activity of human immunodeficiency virus antibody positive (HIV+) individuals with some remaining NK lytic ability was significantly augmented by leu-enkephalin concentrations of 10(-10) and 10(-8) M (n = 7). HIV+ patients with no measurable basal level of NK activity (n = 3) were not responsive to stimulation with leu-enkephalin. Human immunodeficiency virus antibody negative (HIV-) individuals (n = 4) responded in a pattern similar to normals. In addition, naloxone, an antagonist of alkaloid and peptide opiates including leu-enkephalin, displayed the properties of an antagonist/agonist, reflecting the immunoregulatory capacities of the endogenous opiate system.


Changes in intracellular Na+ during Na,K pump inhibition in sheep cardiac tissues.
The differences in inotropic and toxic sensitivities of cardiac ventricular tissue to cardiac glycosides were investigated in order to determine whether or not the reportedly greater sensitivity of Purkinje fibers compared to myocardium is the result of a fundamentally different response to Na,K pump inhibition. I measured the changes in intracellular Na+ activity (aiNa) in the two tissue types simultaneously during exposure to actodigin (4.0 microM) and ouabain (0.5 microM) under quiescent conditions. A sheep papillary muscle and a Purkinje fiber from the same heart were placed in an experimental chamber and measurements of aiNa from both were obtained with Na+ -sensitive microelectrodes. In five experiments in which all electrode impalements were successfully maintained, actodigin caused similar changes in aiNa in the two tissues (from 7.2 +/- 1.0 mM in control to 12.9 +/- 1.9 mM in the presence of drug in papillary muscles compared to 7.3 +/- 0.3 mM in control and 13.2 +/- 1.0 mM in Purkinje fibers; means +/- S.E.M.). After washout, exposure to ouabain increased aiNa in both papillary muscles and in Purkinje fibers (from 7.2 +/- 0.7 mM in control and 16.2 +/- 1.4 mM during exposure to drug in papillary muscles compared to 7.4 +/- 0.3 mM and 14.9 +/- 0.8 mM in Purkinje fibers). In fact, ouabain caused a greater increase of aiNa in papillary muscles than in Purkinje fibers (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Pile Driving at the New Bridge at Tappan Zee: Potential Environmental Impacts.
A new bridge will be constructed to replace the aging Tappan Zee Bridge over the Hudson River in New York. Construction will potentially result in hydroacoustic impacts to the local fish fauna. As a consequence, a substantial environmental impact analysis had to be conducted to obtain construction permits. This paper describes the process of environmental analysis and some of the results of the studies that led up to the final permitting. The process included modeling of pile-driving acoustics, analysis of river ambient noise, analysis of test piling, and observations on fish behavior during these tests.


Assessment of osseous corridor for transiliac-transsacral screws and clinical applications: Computational simulation study.
Transiliac-transsacral (TITS) screw fixation might be necessary in some cases involving the vertical shearing injuries with transforaminal fracture and bilateral posterior ring injuries. However, the possibility of S1 TITS screw should be preoperatively assessed because the pelvic ring injuries with sacral dysmorphism had the insufficient osseous corridors. AxWS2 may predict the possibility of TITS screw fixation and be used as the new indicator to discriminate the sacral dysmorphism. The conventional CT images of eighty-two cadaveric pelvis imported into Mimics® software to reconstruct three-dimensional (3D) models. A 7.0 mm-sized screw was processed into a 3D model using a 3D-sensor at actual size and virtually implanted as S1 and S2 TITS screw using Mimics® software. The cortical violation around screw path was evaluated using 3D biplanar and conventional CT images. The osseous corridor widths around TITS screws were measured in the axial plane images and defined as AxWS1 and AxWS2, respectively. Despite no cortical violation in S2 of all models, cortical violation of S1 TITS screw was found in 20 models. Of them, 14 models (impossible models) were identified in the 3D biplanar images, and all 20 models (CT-violation models) were identified only in CT axial plane images. AxWS1 was<7mm in the impossible models and<9.0mm in the CT-violation models. AxWS2 negatively correlated with AxWS1 (R -0.450, p<0.01). By receiver operating characteristic curve analysis to identify the CT-violation model using AxWS2, the cut-off value of AxWS2 was 13.32mm (sensitivity 0.70, specificity 0.70). By using AxWS2, the possibility of S1 TITS screw fixation could be predicted and safely placed without cortical violation, if AxWS2 was less than 13mm. Considering the negative relationship with AxWS1, AxWS2 should be used as a new indicator to predict safe S1 TITS screw fixation. III, controlled laboratory study.


Computer modeling for pharmacological treatments for dystonia.
Dystonia is a movement disorder that produces involuntary muscle contractions. Current pharmacological treatments are of limited efficacy. Dystonia, like epilepsy is a disorder involving excessive activty of motor areas including motor cortex and several causal gene mutations have been identified. In order to evaluate potential novel agents for multitarget therapy for dystonia, we have developed a computer model of cortex that includes some of the complex array of molecular interactions that, along with membrane ion channels, control cell excitability.


Symptomatic enhanced myometrial vascularity after medically managed early miscarriage or abortion. A case series.
This case series evaluates clinical outcomes and sonographic features of symptomatic enhanced myometrial vascularity developed after either first trimester medical abortion or miscarriage management. All cases were followed until spontaneous resolution. Ultrasonography alongside persistent low serum β-HCG supports enhanced myometrial vascularity diagnosis and expectant management is a feasible approach.


Novel application of heuristic optimisation enables the creation and thorough evaluation of robust support vector machine ensembles for machine learning applications.
Today's researchers have access to an unprecedented range of powerful machine learning tools with which to build models for classifying samples according to their metabolomic profile (e.g. separating diseased samples from healthy controls). However, such powerful tools need to be used with caution and the diagnostic performance of models produced by them should be rigorously evaluated if their output is to be believed. This involves considerable processing time, and has hitherto required expert knowledge in machine learning. By adopting a constrained nonlinear simplex optimisation for the tuning of support vector machines (SVMs) we have reduced SVM training times more than tenfold compared to a traditional grid search, allowing us to implement a high performance R package that makes it possible for a typical bench scientist to produce powerful SVM ensemble classifiers within a reasonable timescale, with automated bootstrapped training and rigorous permutation testing. This puts a state-of-the-art open source multivariate classification pipeline into the hands of every metabolomics researcher, allowing them to build robust classification models with realistic performance metrics.


A new simple and high-yield synthesis of suberoylanilide hydroxamic acid and its inhibitory effect alone or in combination with retinoids on proliferation of human prostate cancer cells.
We have developed a procedure for the synthesis of N-hydroxy-N(1)-phenyloctanediamide (suberoylanilide hydroxamic acid (SAHA)), providing the product in 79.8% yield. SAHA is a potent inhibitor of histone deacetylase, induces differentiation and/or apoptosis in certain transformed cells in culture, and suppressed the growth of human prostate cancer LNCaP and PC-3 cell lines. The combination of SAHA with other compounds inhibited cell proliferation of LNCaP cells in additive fashion and resulted in synergistic growth inhibition.


Multi-drug and methicillin resistance of staphylococci from canine patients at a veterinary teaching hospital (2006-2011).
Over the past 10 years, an increase in methicillin and multi-drug resistant staphylococcal species has been identified worldwide and anecdotally reported within our veterinary teaching hospital. To determine the methicillin resistance (MR) and multi-drug resistance (MDR) patterns of staphylococcal species isolated from canine patients between 2006 and 2011. Staphylococcal isolates (n = 1069) were cultured from the canine patient population of the veterinary teaching hospital. The susceptibility reports of Staphylococcus pseudintermedius, S. aureus, S. schleiferi v. coagulans, S. schleiferi v. schleiferi, and other coagulase-negative staphylococci (CoNS) were assessed. Isolates were organized into five site categories. Isolates were scored on a 0-10 scale based on resistance to antimicrobial classes, with MDR classified as an isolate scoring a value ≥3. Statistical analysis included χ(2), Fisher's exact test, and ANOVA with mean square and post hoc analysis; p < 0.05 was significant. S. pseudintermedius (76.6%), S. aureus (15.5%), S. schleiferi v. coagulans (5.7%), S. schleiferi v. schleiferi (1.2%), and CoNS (0.9%) isolation was observed. MR occurred in 11.4% of all combined isolates, with no difference between sites and years. Of the S. pseudintermedius isolates, 4.5% were methicillin resistant. Of all the isolates, 27.5% were MDR. The mean resistance score of S. pseudintermedius isolates increased significantly comparing 2006 and 2008 (p = 0.0006) and 2006 and 2009 (p = 0.0009). The mean score of all combined isolates increased significantly comparing 2006 and 2008 (p = 0.001). MR staphylococci isolation is similar when compared to other studies. However, increased MDR isolation is of greater concern and high-scoring MDR staphylococci will limit our future antimicrobial choices.


Metallothionein-Kidney Bean Polyphenol Complexes Showed Antidiabetic Activity in Type 2 Diabetic Rats by Improving Insulin Resistance and Regulating Gut Microbiota.
Previous studies have shown that interaction between polyphenols and proteins can benefit health, but the mechanism of its antidiabetic effect has not been thoroughly elucidated. Therefore, this study aimed to investigate the impact of the metallothionein (MT)-kidney bean polyphenol complex on the blood glucose levels and gut microbiota of rats with type 2 diabetes mellitus (T2DM) induced by a high-fat diet combined with streptozotocin (STZ). After 7 weeks of intervention, the MT-kidney bean polyphenol complex can significantly improve the loss of body weight, the increase in blood glucose and blood lipids, and insulin resistance caused by T2DM in rats. In addition, it can effectively alleviate the damage to the pancreas and liver in rats. The MT-kidney bean polyphenol complex also significantly increased the concentrations of six short-chain fatty acids (SCFAs) in the intestinal contents of rats, especially acetic acid, propionic acid, and butyric acid (296.03%, 223.86%, and 148.97%, respectively). More importantly, the MT-kidney bean polyphenol complex can significantly reverse intestinal microflora dysbiosis in rats caused by T2DM, increase intestinal microorganism diversity, improve the abundance of various beneficial bacteria, and reshape the gut microbiota. In summary, the hypoglycemic effect of the MT-kidney bean polyphenol complex and its possible mechanism was expounded in terms of blood glucose level, blood lipid level, and gut microbiota, providing a new perspective on the development of the MT-kidney bean polyphenol complex as functional hypoglycemic food.


Plasma membrane-chloroplast interactions activated by the hyperpolarizing response in characean cells.
Signaling pathways in plant cells often comprise electrical phenomena developing at the plasma membrane. The action potentials in excitable plants like characean algae have a marked influence on photosynthetic electron transport and CO2 assimilation. The internodal cells of Characeae can also generate active electrical signals of a different type. The so called hyperpolarizing response develops under the passage of electric current whose strength is comparable to physiological currents circulating between nonuniform cell regions. The plasma membrane hyperpolarization is involved in multiple physiological events in aquatic and terrestrial plants. The hyperpolarizing response may represent an unexplored tool for studying the plasma membrane-chloroplast interactions in vivo. This study shows that the hyperpolarizing response of Chara australis internodes whose plasmalemma was preliminary converted into the K+-conductive state induces transient changes in maximal (Fm') and actual (F') fluorescence yields of chloroplasts in vivo. These fluorescence transients were light dependent, suggesting their relation to photosynthetic electron and H+ transport. The cell hyperpolarization promoted H+ influx that was inactivated after a single electric stimulus. The results indicate that the plasma membrane hyperpolarization drives transmembrane ion fluxes and modifies the ionic composition of cytoplasm, which indirectly (via envelope transporters) affects the pH of chloroplast stroma and chlorophyll fluorescence. Remarkably, the functioning of envelope ion transporters can be revealed in short-term experiments in vivo, without growing plants on solutions with various mineral compositions.


Predicting the emergence of malignant brain oedema in acute ischaemic stroke: a prospective multicentre study with development and validation of predictive modelling.
We aimed to develop and validate a prognostic model for predicting malignant brain oedema in patients with acute ischaemic stroke in a real-world setting of practice. A prospective multicentre study enrolled adult patients with acute ischaemic stroke with brain CT < 24 h of onset of symptoms admitted to nine tertiary-level hospitals in China between September 2017 and December 2019. Malignant brain oedema was defined as any patient who had decompressive craniectomy, discharge in coma, or in-hospital death attributed to symptomatic brain swelling. The derivation cohort was a consecutive cohort of patients from one centre and the validation cohort was non-consecutive patients from the other centres. Multivariable logistic regression was used to define independent predictors from baseline clinical characteristics, imaging features, complications, and management. A web-based nomogram and a risk score were developed based on the final model. Model performance was assessed for discrimination and calibration in both derivation and validation cohorts. The study is registered, NCT03222024. Based on the derivation cohort (n = 1627), the model was developed with seven variables including large infarct (adjusted odds ratio [OR] 40.90, 95% CI 20.20-82.80), National Institutes of Health Stroke Scale (NIHSS) score (OR 1.09, 1.06-1.12), thrombolysis (OR 2.11, 1.18-3.78), endovascular treatment (OR 2.87, 1.47-5.59), pneumonia (OR 2.47, 1.53-3.97), brain atrophy (OR 0.57, 0.37-0.86), and recanalisation (OR 0.36, 0.17-0.75). The classification threshold of a predicted probability ≥0.14 showed good discrimination and calibration in both derivation cohort (area under the receiver-operating curve [AUC] 0.90, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation cohort (n = 556, AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95). The risk score based on this model had a total point that ranged from -1 to 20, with an optimal score of ≥10 showing good discrimination and calibration in both derivation (AUC 0.89, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation (AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95) cohorts. The INTEP-AR model (i.e. large Infarct, NIHSS score, Thrombolysis, Endovascular treatment, Pneumonia, brain Atrophy, and Recanalisation) incorporating multiple clinical and radiological characteristics has shown good prognostic value for predicting malignant brain oedema after acute ischaemic stroke. National Natural Science Foundation of China; Science and Technology Department of Sichuan Province; West China Hospital.


Assessment of extracting molars and premolars after root canal treatment: A retrospective study.
The loss of dentition after root canal treatment is a multifactorial entity which might differ between different teeth. The extraction can be more critical, as well as the rehabilitation options. To analyze if the etiology of extracting root canal treated teeth is different between premolars and molars. The study included a total of 403 cases with non-surgical root canal therapy (NSRCT) and crown coverage that was referred to the oral surgery clinic for extraction. Tooth type, patient's age, gender, time since treatment completion, and the reason for extractions were recorded and analyzed. The most frequently extracted teeth were molars (55.6%), followed by premolars (30.3%) and anterior teeth (14.1%). The reasons for extraction were subgingival decay (SGD) (62.5%), vertical root fractures (VRF) (25.3%), and patient demands after uncomfortableabscess discharge (12.2%). Most of the teeth survived between 13 and 36 months after NSRCT. The statistical power of 0.92 was demonstrated, and a P-value of less than 0.05 presented significant correlations. Molars were extractedafter NSRCT due to SGD followed by premolars, which were extracted due to VRF. Special care should be taken while planning NSRCT treatment for molars, in particular, with emphasis on the importance of oral hygiene and follow-up visits.


Role of immune complexes in alteration of lymphocyte subpopulation numbers and functions in experimental leprosy.
Swiss albino mice (normal as well as thymectomised and irradiated were inoculated into the footpads with Mycobacterium leprae and divided into two main phases of study. Phase I comprised of animals not given preformed immune complexes (IC). Uninfected controls were however included. Phase II consisted of animals given in vitro prepared IC at zero day period (OdIC), three month period (3mIC) or six month period (6mIC) to both uninfected and infected groups. Splenic lymphocytes were isolated to quantify T and B cells and their responses to M. leprae antigen and four different mitogens. Significant decrease in T cell counts and blast transformation was seen in the M. leprae infected animals which were also administered with immune complexes. Immunosuppression by IC was therefore seen to be enhanced in the presence of M. leprae infection.


Cobalt Catalyzed C-H and N-H Bond Annulation of Sulfonamide with Terminal and Internal Alkynes.
Chelate assisted cobalt catalyzed C-H and N-H annulation of aryl sulfonamide with terminal and internal alkynes is reported. Very high regioselectivity and excellent functional group tolerance were achieved using oxygen as a co-oxidant. The reaction is scalable under mild conditions.


A novel and rapid method for fatty acid preparation by the lipase-catalyzed hydrolysis of Phoenix tree seeds.
Fatty acids are the precursors for the production of fuels, oleochemicals and special health care products. In this study, a novel rapid method for fatty acid (FA) preparation by the enzymatic hydrolysis of Phoenix tree seed, an undeveloped woody oil seed, was developed. High-temperature GC with flame ionization detector (FID) and the hydrolysis ratio were used to monitor reaction progress. Enzyme screening and the effect of reaction variables on the hydrolysis of seeds were evaluated and optimized by response surface methodology. The results showed that among the tested enzymes, Lipozyme TLIM showed the greatest amount of hydrolysis of Phoenix tree seed. FAs can be rapidly prepared by one-step hydrolysis of Phoenix tree seeds using Lipozyme TLIM as the biocatalyst. Under the optimized conditions (6% enzyme load, 1:8 mass ratio of seed to water, 47.7 °C and 16 min), the maximum hydrolysis ratio (96.4 ± 1.1%) can be achieved. The effect of reaction variables on the hydrolysis decreased in the following order: reaction time > enzyme load > substrate ratio of seed to water > reaction temperature. This work provides a novel and rapid method for FA preparation from oil seeds.


Clinical and experimental aspects of hormone receptors in breast carcinoma patients.
Estrogen (ER) and progesterone (PgR) receptor contents were determined in 214 patients with primary mammary carcinoma. Premenopausal and postmenopausal females (43 and 48%, respectively) were found to be ER and PgR positive. ER levels between 100 and 500 fmol/mg protein were observed in 37% postmenopausal and 14% premenopausal patients, respectively. ER distribution between lymph node-positive and -negative patients did not differ significantly. Subjects without detectable ER had recurrences earlier than did subjects with ER. On the other hand, no differences in recurrence rates were noted when PgR-positive and -negative patients were compared. In addition, the determination of ER did not permit selection of patients for adjuvant cytotoxic chemotherapy. Furthermore, the action of tamoxifen was investigated in the rat pituitary as a model system. Tamoxifen was found to act as antiestrogen at the level of transcription by inhibiting the accumulation of estrogen-stimulated preprolactin mRNA. Combined data suggest that patients with positive lymph nodes and positive receptors may benefit from combined endocrine plus cytotoxic adjuvant chemotherapy.


Immunohistochemical amplification of mCherry fusion protein is necessary for proper visualization.
Fluorescent reporter proteins are a powerful tool being increasingly integrated into biological experiments. Their utility spans techniques such as live-cell imaging, validating transgene expression, and studying cell-type specific anatomy. As these reporters become more widely used, it is necessary to fully understand their benefits and limitations. One such recently developed red fluorescent protein, mCherry, has been well utilized due to its stability, brightness, and pH resistance. In the course of an experiment using the fluorescent reporter protein mCherry fused to a G-protein coupled receptor (mCherry fusion protein), our lab discovered a notable inability for the fusion protein to faithfully produce fluorescent signal representative of its expression in fixed tissue. Here, we demonstrate the importance of immunohistochemical amplification in tissue injected with various adeno-associated viruses (AAVs), containing mCherry fusion protein as a reporter. Our findings demonstrate that antibody amplification consistently provides a stronger signal when mCherry fusion protein is used as a reporter protein.