The structure of medical malpractice decision-making in Japan.
The article summarises the problems in the medical malpractice litigation systems in the United Kingdom and Japan, demonstrating the similarities and identifying the length of time between initiating an action and its decision and other factors responsible for lengthy litigation. Based on analysis of decisions of medical malpractice cases between 1986 and 1998 in Japan, the functioning of the Japanese medical malpractice litigation system is discussed. Lengthy litigation is shown to be correlated with outcome and implies that the Japanese medical dispute resolution mechanism favours those who can endure lengthy litigation, namely the defendants, who are physicians or hospitals. In view of the similarities between the two systems, it is likely that the same bias--that the wealthier party in the litigation is more likely to win the case--also occurs in medical malpractice litigation in the United Kingdom and Australia.


[Delirium in the intensive care unit].
The prevalence of delirium in the Intensive Care Unit (ICU) is reported to vary from 20 to 80 %. Delirium in the ICU is not only a frightening experience for the patient and his or her family, it is also a challenge for the nurses and physicians taking care of the patient. Furthermore, it is also associated with worse outcome, prolonged hospitalisation, increased costs, long-term cognitive impairment and higher mortality rates. Thus, strategies to prevent ICU-delirium in addition to the early diagnosis and treatment of delirium are important. The pathophysiology of delirium is still incompletely understood, but numerous risk factors for the development of delirium have been identified in ICU-patients, among which are potentially modifiable factors such as metabolic disturbances, hypotension, anaemia, fever and infection. Key factors are the prevention and management of common risk factors, including avoiding overzealous sedation and analgesia and creating an environment that enhances reintegration. Once delirium is diagnosed, treatment consists of the use of typical and atypical antipsychotics. Haloperidol is still the drug of choice for the treatment of delirium and can be given intravenously in incremental doses of 1 to 2 to 5 (to 10) mg every 15 - 20 minutes.


Release of inactive renin from human fetal membranes and isolated trophoblasts.
Human chorio-amnion from term pregnancy was perfused in vitro in a dual perfusion apparatus. Renin released from the fetal membranes was almost entirely in the form of inactive renin (IR) (trypsin-activated). IR was released from both the chorion side and the amnion side. IR introduced on the chorion side of the chorio-amnion did not appear on the amnion side. When cells isolated from term amnion and chorion were grown in tissue culture, IR was released continuously from chorionic cells but not from amnionic cells. The release of IR did not parallel the release of LDH from cultured chorion cells. Exposure to low calcium medium (with or without EGTA) decreased IR release while LDH release increased (or remained constant). Exposure to the calcium ionophore (A 23187) resulted in a marked decrease in IR release. The release of IR from chorionic cells shows some similarities to the release of HCG from trophoblasts. It is expected that IR release from the chorion will show some similarities to R release from the kidney as well as major differences. The function, regulation, and processing of chorionic IR remain to be elucidated.


Toward a construct validation of the Rorschach.
The debate over the validity of the Rorschach has been lengthy but unresolved. Major reasons for the lack of consensus and conclusion are the absence of agreement about, how validation research should be conducted and the failure to identify appropriate criteria for subsequent evaluation. A construct validation model for the Rorschach is presented, with guidelines for proper implementation. The difficulties in establishing the optimal relationship between theory, research design, and clinical practice arc discussed. Recommendations for a resolution of these difficulties are presented.


A morphologic study of Vietnam veterans.
The possibility that service in Vietnam has had an adverse effect on Vietnam veterans and is the cause of some of their current illnesses has been a controversial issue in the post-Vietnam period. Addressing this problem, a pathology study has been carried out at the Armed Forces Institute of Pathology (AFIP). Pathologic diagnoses found in Vietnam veterans have been compared with a control group of contemporary veterans without Vietnam service. This has revealed no statistically significant or unexplained differences in their demographic, anatomic, or morphologic findings. The essential similarity of their disease profiles to date fails to suggest the presence of any unique environmental factor that might have acted on the Vietnam group.


PIST regulates the intracellular trafficking and plasma membrane expression of cadherin 23.
The atypical cadherin protein cadherin 23 (CDH23) is crucial for proper function of retinal photoreceptors and inner ear hair cells. As we obtain more and more information about the specific roles of cadherin 23 in photoreceptors and hair cells, the regulatory mechanisms responsible for the transport of this protein to the plasma membrane are largely unknown. PIST, a Golgi-associated, PDZ domain-containing protein, interacted with cadherin 23 via the PDZ domain of PIST and the C-terminal PDZ domain-binding interface (PBI) of cadherin 23. By binding to cadherin 23, PIST retained cadherin 23 in the trans-Golgi network of cultured cells. The retention was released when either of the two known cadherin 23-binding proteins MAGI-1 and harmonin was co-expressed. Similar to MAGI-1 and harmonin, PIST was detected in mouse inner ear sensory hair cells. PIST binds cadherin 23 via its PDZ domain and retains cadherin 23 in trans-Golgi network. MAGI-1 and harmonin can compete with PIST for binding cadherin 23 and release cadherin 23 from PIST's retention. Our finding suggests that PIST, MAGI-1 and harmonin collaborate in intracellular trafficking of cadherin 23 and regulate the plasma membrane expression of cadherin 23.


Laser technology in urologic oncology.
Laser technology has been used in Urology since the 80s with a lot of different applications in endoscopic and open surgery. With the developments of the technology and the introduction of new active medium and source of laser energy, this technology have become the gold standard not only in stone surgery but even in benign prostate enlargement (BPE) surgical treatment. Regarding urologic oncology, laser energy has now reached an important role in focal therapy and in conservative treatment. The possibility of having better functional outcomes without any relevant impact on oncological results led to an increased use of laser in penile surgery, with a significant mention in urological guidelines for this option. In urothelial cancers as well, both in conservative management of upper tract tumors that in the treatment of non muscle invasive bladder cancer, a clear role of these relatively new source of energy have been demonstrated. Finally, both in prostate that in renal cancer the strategy of focal therapy may take advantage from this precise and fine technology. In this review we analyzed and described the applications of laser energy in urological cancers with a specific focus on penile, urothelial and prostate cancer.


Coronary microcirculatory pathophysiology: can we afford it to remain a black box?
Coronary microvascular networks play the key role in determining blood flow distribution in the heart. Matching local blood supply to tissue metabolic demand entails continuous adaptation of coronary vessels via regulation of smooth muscle tone and structural dilated vessel diameter. The importance of coronary microcirculation for relevant pathological conditions including angina in patients with normal or near-normal coronary angiograms [microvascular angina (MVA)] and heart failure with preserved ejection fraction (HFpEF) is increasingly recognized. For MVA, clinical studies have shown a prevalence of up to 40% in patients with suspected coronary artery disease and a relevant impact on adverse cardiovascular events including cardiac death, stroke, and heart failure. Despite a continuously increasing number of corresponding clinical studies, the knowledge on pathophysiological cause-effect relations involving coronary microcirculation is, however, still very limited. A number of pathophysiological hypotheses for MVA and HFpEF have been suggested but are not established to a degree, which would allow definition of nosological entities, stratification of affected patients, or development of effective therapeutic strategies. This may be related to a steep decline in experimental (animal) pathophysiological studies in this area during the last 15 years. Since technology to experimentally investigate microvascular pathophysiology in the beating heart is increasingly, in principle, available, a concerted effort to build 'coronary microcirculatory observatories' to close this gap and to accelerate clinical progress in this area is suggested.


The pattern of gene expression and gene dose profiles of 6-Mercaptopurine- and 6-Thioguanine-resistant human leukemia cells.
Exposure of MOLT4 human T-cell leukemia cells to 6-Mercaptopurine (6-MP) and 6-Thioguanine (6-TG) resulted in acquired resistance associated with attenuated expression of the genes encoding concentrative nucleoside transporter 3 (CNT3) and equilibrative nucleoside transporter 2 (ENT2). To identify other alterations at the RNA and DNA levels associated with 6-MP- and 6-TG resistance, we compared here the patterns of gene expression and DNA copy number profiles of resistant sublines to those of the parental wild-type cells. The mRNA levels for two nucleoside transporters were down-regulated in both of the thiopurine-resistant sublines. Moreover, both of these cell lines expressed genes encoding the enzymes of purine nucleotide composition and synthesis, including adenylate kinase 3-like 1 and guanosine monophosphate synthetase at significantly lower levels than wild-type cells. In addition, expression of the mRNA for a specialized DNA polymerase, human terminal transferase encoded by the terminal deoxynucleotidyl transferase (DNTT) gene, was 122- and 93-fold higher in 6-TG- and 6-MP-resistant cells, respectively. The varying responses to 6-MP- and 6-TG observed here may help identify novel cellular targets and modalities of resistance to thiopurines, as well as indicating new potential approaches to individualization therapy with these drugs.


Inhibition of CaM kinase II activation and force maintenance by KN-93 in arterial smooth muscle.
Ca(+)/calmodulin-dependent protein kinase II (CaM kinase II) has been implicated in the regulation of smooth muscle contractility. The goals of this study were to determine: 1) to what extent CaM kinase II is activated by contractile stimuli in intact arterial smooth muscle, and 2) the effect of a CaM kinase II inhibitor (KN-93) on CaM kinase II activation, phosphorylation of myosin regulatory light chains (MLC(20)), and force. Both histamine (1 microM) and KCl depolarization activated CaM kinase II with a time course preceding maximal force development, and suprabasal CaM kinase II activation was sustained during tonic contractions. CaM kinase II activation was inhibited by KN-93 pretreatment (IC(50) approximately 1 microM). KN-93 inhibited histamine-induced tonic force maintenance, whereas early force development and MLC(20) phosphorylation responses during the entire time course were unaffected. Both force development and maintenance in response to KCl were inhibited by KN-93. Rapid increases in KCl-induced MLC(20) phosphorylation were also inhibited by KN-93, whereas steady-state MLC(20) phosphorylation responses were unaffected. In contrast, phorbol 12,13-dibutyrate (PDBu) did not activate CaM kinase II and PDBu-stimulated force development was unaffected by KN-93. Thus KN-93 appears to target a step(s) essential for force maintenance in response to physiological stimuli, suggesting a role for CaM kinase II in regulating tonic contractile responses in arterial smooth muscle. Pharmacological activation of protein kinase C bypasses the KN-93 sensitive step.


Management simulations for Lean healthcare: exploiting the potentials of role-playing.
Purpose The purpose of this paper is to investigate the potentials of role-playing (RP) both in training healthcare (HC) professionals to implement tools and improvement actions based on Lean principles, and in supporting group discussion and the sharing of different competencies for the development of Lean HC. Design/methodology/approach The paper presents the case study of an RP simulation called LEAN HEALTHCARE LAB, which is used to train HC professionals at Siena University Hospital. The paper reports and discusses the results of a specific two-day simulation session and of a questionnaire that was distributed to gather feedback from the participants. Findings The paper verifies the potentials of RP to be a powerful educational and training tool that is able to stimulate the HC participants to apply Lean thinking principles and share their competencies in collaborative decision-making processes. Research limitations/implications The study provides data in reference to one single simulation session, although the game has already been applied several times in different HC organizations with very similar outcomes. Moreover, a more in-depth analysis of players' perceptions and decisions could be performed using different tools in addition to the adopted questionnaire. Practical implications RP games (RPGs) are effective training and educational tools for HC professionals. They offer benefits and learning conditions which are definitely different if compared with more conventional education programs for HC professionals. Originality/value While previous studies have extensively discussed the potentialities of RPG and simulations in training programs, only a few articles have discussed the RP adoption for Lean thinking and even less to educate HC professionals on Lean principles and tools.


Breaking through the acid barrier: an orchestrated response to proton stress by enteric bacteria.
The ability of enteropathogens such as Salmonella and Escherichia coli to adapt and survive acid stress is fundamental to their pathogenesis. Once inside the host, these organisms encounter life-threatening levels of inorganic acid (H+) in the stomach and a combination of inorganic and organic acids (volatile fatty acids) in the small intestine. To combat these stresses, enteric bacteria have evolved elegant, overlapping strategies that involve both constitutive and inducible defense systems. This article reviews the recent progress made in understanding the pH 3 acid tolerance systems of Salmonella and the even more effective pH 2 acid resistance systems of E. coli. Focus is placed on how Salmonella orchestrates acid tolerance by modulating the activities or levels of diverse regulatory proteins in response to pH stress. The result is induction of overlapping arrays of acid shock proteins that protect the cell against acid and other environmental stresses. Most notable among these pH-response regulators are RpoS, Fur, PhoP and OmpR. In addition, we will review three dedicated acid resistance systems of E. coli, not present in Salmonella, that allow this organism to survive extreme (pH 2) acid challenge.


Quality of life, postnatal depression and baby gender.
To study the impact of postnatal depression on the quality of life of young French mothers and to evaluate if the gender of their child influences this. Postnatal depression (PND) constitutes a major public health problem considering its high prevalence and consequences upon quality of life and parental skills. This research is a cross-sectional study during the postnatal period. This study was carried out during a two-month period. Data were collected by interview and questionnaires. The authors compared the prevalence rate of PND and life quality in a cohort of 181 women and measured the short-term impact of the child's birth. Postnatal depression strongly negatively influences all dimensions of life quality explored through the SF36, e.g. physical functioning (PF), physical Role (RP), bodily pain (BP), mental health (MH), emotional role (RE), social functioning (SF), vitality (VT), general health (GH), standardized physical component (PCS) and standardized mental component (MCS). The baby's gender (having a boy) also significantly reduces quality of life, irrespective of depressive state. There is a relationship between baby gender and PND. This research is the first to show that the birth of a boy reduces several dimensions of the mothers' quality of life. The importance of the impairment of quality of life in case of PND, as well as its effects on mother-child interaction, could justify prevention programs and early psychotherapeutic care. Further research needs to explore the effectiveness of programmes targeting the construction of parenting skills as a preventative measure against PND, especially for parents of boys.


Genetic Manipulation and Bioreactor Culture of Plants as a Tool for Industry and Its Applications.
In recent years, there has been a considerable increase in interest in the use of transgenic plants as sources of valuable secondary metabolites or recombinant proteins. This has been facilitated by the advent of genetic engineering technology with the possibility for direct modification of the expression of genes related to the biosynthesis of biologically active compounds. A wide range of research projects have yielded a number of efficient plant systems that produce specific secondary metabolites or recombinant proteins. Furthermore, the use of bioreactors allows production to be increased to industrial scales, which can quickly and cheaply deliver large amounts of material in a short time. The resulting plant production systems can function as small factories, and many of them that are targeted at a specific operation have been patented. This review paper summarizes the key research in the last ten years regarding the use of transgenic plants as small, green biofactories for the bioreactor-based production of secondary metabolites and recombinant proteins; it simultaneously examines the production of metabolites and recombinant proteins on an industrial scale and presents the current state of available patents in the field.


Assimilate translocation and expression of sucrose transporter, OsSUT1, contribute to high-performance ripening under heat stress in the heat-tolerant rice cultivar Genkitsukushi.
High temperature reduces the grain quality of rice, a situation likely to become more frequent because of global warming. We studied the effects of high-temperature stress on grain quality of heat-tolerant cultivar 'Genkitsukushi' and heat-sensitive cultivar 'Tsukushiroman'. When day/night temperatures were 31/26 °C from heading until maturity, the grain quality of 'Genkitsukushi' was rated at the first inspection grade (high quality), whereas 'Tsukushiroman' showed a remarkable increase in the percentage of white immature kernels (low quality). Nonstructural carbohydrate content in the stem of 'Genkitsukushi' the early maturation was significantly higher than in 'Tsukushiroman' and greatly decreased under high temperature. From 14 to 21 days after heading, the expression of the sucrose transporter gene, OsSUT1, was higher in the stem of 'Genkitsukushi' grown under high temperature than in 'Tsukushiroman'. In addition, the expression of OsSUT1 in the grains of 'Genkitsukushi' was significantly higher than in 'Tsukushiroman' during the ripening period. These results indicate that sugar transport functions more effectively in 'Genkitsukushi' than in 'Tsukushiroman', and that the effectiveness of sugar transport contributes to maintaining high grain quality in 'Genkitsukushi' under high-temperature conditions.


Aldosterone: a telling case of fruitful interplay between biological and clinical research.
Aldosterone, discovered thirty years ago, has rapidly gained an enviable status among clinicians as well as biologists: this hormone is the main regulator of extracellular fluid volume--essentially through its effect on sodium retention in the distal parts of the nephron. This aspect has been fruitfully approached by means of (amphibian) epithelia carrying out transcellular sodium transport and resembling in this respect the distal renal tubule. Recent results suggest that, at least after prolonged incubation, not only is sodium entry (at the apical border) facilitated by aldosterone, but the latter steroid also somehow improves the handling of the ions by the "pump" located at the basal-lateral border. As a consequence, the target cells exposed to aldosterone are optimally geared for enhanced transcellular sodium transport. Biochemically, both processes depend on the standard pattern of steroid hormone action: after interaction of aldosterone with protein receptors(s) present in the cytoplasm of target cells, and migration of the resulting complex to their nucleus, synthesis of specific messenger ribonucleis acid is stimulated which leads to increased synthesis of proteins eventually responsible for the physiological response. An intriguing aspect of the concerted response to aldosterone documented in amphibian sodium-transporting epithelia, is that both cell borders of target cells are not influenced simultaneously: this is currently investigated [Beauwens et al. 1982b].


Physician compliance with tetanus guidelines for admitted versus discharged patients.
The Advisory Committee of Immunization Practice (ACIP) has established guidelines for tetanus immunoprophylaxis for patients who present to the emergency department (ED) with wounds. We assessed physician compliance with these guidelines for admitted versus discharged patients. The data in this study comes from one institution involved in a recently published prospective observational study that was conducted at 5 university-affiliated hospitals. Of 400 patients enrolled, 65/397 (16.3%) did not receive tetanus immunoprophylaxis in accordance with ACIP guidelines. Emergency physicians were less likely to adhere to the ACIP tetanus guidelines when admitting patients to the hospital. Of patients discharged, (89%), 292 of 325 were treated in accordance with ACIP guidelines compared with 39/71 (55%) of admitted patients (P < 0.001). Admitted patients were also more likely to sustain tetanus-prone wounds. Despite a propensity to present with tetanus-prone wounds, patients admitted to the hospital were less likely to receive tetanus immunoprophylaxis in accordance with ACIP guidelines.


Osteopontin expression in normal skin and non-melanoma skin tumors.
Osteopontin (OPN) is an adhesive, matricellular glycoprotein, whose expression is elevated in many types of cancer and has been shown to facilitate tumorigenesis in vivo. To understand the role of OPN in human skin cancer, this study is designed to determine whether OPN is expressed in premalignant [solar/actinic keratosis (AK)] and in malignant skin lesions such as squamous cell carcinomas (SCC) and basal cell carcinomas (BCC), as well as in normal skin exposed or not exposed to sunlight. Immunohistochemical analyses showed that OPN is expressed in SCC (20/20 cases) and in AK (16/16 cases), which are precursors to SCC, but is absent or minimally expressed in solid BCC (17 cases). However, positive staining for OPN was observed in those BCC that manifest differentiation toward epidermal appendages such as keratotic BCC. In sunlight-exposed normal skin, OPN is minimally expressed in the basal cell layer, but in contrast to those not exposed to sunlight, OPN is more prominent in the spinous cell layer with increasing intensity toward the granular cell layer. Additionally, OPN is expressed in the hair follicles, sebaceous glands, and sweat glands of normal skin. In conclusion, these data suggest that OPN is associated with keratinocyte differentiation and that it is expressed in AK and SCC, which have metastatic potential, but minimally expressed in solid BCC.


Identification of US Counties at Elevated Risk for Congenital Syphilis Using Predictive Modeling and a Risk Scoring System.
Although preventable through timely screening and treatment, congenital syphilis (CS) rates are increasing in the United States, occurring in 5% of counties in 2015. Although individual-level factors are important predictors of CS, given the geographic focus of CS, it is also imperative to understand what county-level factors are associated with CS. This is a secondary analysis of reported county CS cases to the National Notifiable Diseases Surveillance System during the periods 2014-2015 and 2016-2017. We developed a predictive model to identify county-level factors associated with CS and use these to predict counties at elevated risk for future CS. Our final model identified 973 (31.0% of all US counties) counties at elevated risk for CS (sensitivity, 88.1%; specificity, 74.0%). County factors that were predictive of CS included metropolitan area, income inequality, primary and secondary syphilis rates among women and men who have sex with men, and population proportions of those who are non-Hispanic black, Hispanic, living in urban areas, and uninsured. The predictive model using 2014-2015 CS outcome data was predictive of 2016-2017 CS cases (area under the curve value, 89.2%) CONCLUSIONS: Given the dire consequences of CS, increasing prevention efforts remains important. The ability to predict counties at most elevated risk for CS based on county factors may help target CS resources where they are needed most.


Geriatric risk and protective factors for serious COVID-19 outcomes among older adults in Shanghai Omicron wave.
Shanghai has been experiencing the Omicron wave since March 2022. Though several studies have evaluated the risk factors of severe infections, the analyses of BA.2 infection risk and protective factors among geriatric people were much limited. This multicentre cohort study described clinical characteristics, and assessed risk and protective factors for geriatric Omicron severe infections. A total of 1377 patients older than 60 were enrolled, with 75.96% having comorbidities. The median viral shedding time and hospitalization time were nine and eight days, respectively. Severe and critical were associated with longer virus clearance time (aOR [95%CI]:0.706 (0.533-0.935), P = .015), while fully vaccinated/booster and paxlovid use shortened viral shedding time (1.229 [1.076-1.402], P = .002; 1.140 [0.019-1.274], P = .022, respectively). Older age (>80), cerebrovascular disease, and chronic kidney disease were risk factors of severe/critical. Fully vaccination was a significant protective factor against severe infections (0.237 [0.071-0.793], P = .019). We found patients with more than two comorbidities were more likely to get serious outcomes. These findings demonstrated that in the elderly older than 60 years old, older age (aged over 80), cerebrovascular disease, and chronic kidney disease were risk factors for severe infection. Patients with more than two comorbidities were more likely to get serious outcomes. Fully vaccinated/booster patients were less likely to be severe and vaccinations could shorten viral shedding time. The limitation of lacking an overall spectrum of COVID-19 infections among elders could be compensated in other larger-scale studies in the future.


Combinable poly(dimethyl siloxane) capillary sensor array for single-step and multiple enzyme inhibitor assays.
We describe a new method for fabricating a capillary-type sensor, called a combinable poly(dimethyl siloxane) (PDMS) capillary (CPC) sensor. The method for preparing the CPC simplifies enzyme inhibitor assays into a simple, single step assay. The sample inhibitor solution is introduced by capillary action. This triggers the spontaneous dissolution of physically adsorbed fluorescent substrates, and the substrate mixes with the inhibitor. This is followed by competitive reaction with insoluble enzyme to give a fluorescence response. CPC is composed of a convex-shaped PDMS stick containing reagents immobilized in an insoluble coating, and a concave-shaped PDMS stick containing reagents immobilized in a soluble coating. Since the concave-shaped PDMS has a deeper channel than the convex structure, combining these PDMS sticks is like closing the zipper of a "freezer bag". This allows easy fabrication of "thin and long" capillary structures containing different reagents inside the same capillary, without the need for precise alignment. This method allows the immobilization of two reactive reagents, such as enzyme and substrate required for a single step assay, which are typically very difficult to immobilize using commercially available conventional capillaries. Furthermore, by simply arraying various CPCs, the CPC sensor allows multiple assays. Here, we carried out a single-step enzyme inhibitor assay using the CPC. In addition, two independent CPCs were arrayed to demonstrate multiple assaying of a protease inhibitor.


A systematic evaluation of the adaptation of depression diagnostic methods for stroke survivors who have aphasia.
One in 3 stroke survivors has aphasia (impaired language comprehension and expressive abilities). Conventionally, depression diagnosis uses language-based methods. We aimed to systematically review methods that have been used to diagnose depression and adaptations to these methods intended for people with aphasia. We systematically reviewed stroke studies (to January 2006) that included a depression diagnosis and individuals with aphasia. We extracted data related to depression diagnostic methods used for individuals with/without aphasia. We sought clarification from authors when required. A total of 60 studies included people with aphasia. Almost half the studies (29/60; 48%) adapted their main depression diagnostic method (most typically a clinical interview and published criteria) for individuals with aphasia. Adaptive methods included: using informants (relatives or staff), clinical observation, modifying questions and visual analogue scales. Evidence of the validity or reliability of these adaptations was rarely reported. However, use of informants or clinical observation did achieve the inclusion of most people with aphasia in the diagnosis of depression. Remaining studies, that did not report adaptive methods, suggested that conventional language-based methods are suitable for individuals with only 'mild' aphasia. People with aphasia can be and have been included in depression diagnostic assessments. However, we suggest that depression and language experts collaborate to develop a more valid method of depression diagnosis for patients with aphasia that has good reliability.


Nonclassical fullerenes with a heptagon violating the pentagon adjacency penalty rule.
Nonclassical fullerenes with heptagon(s) and their derivatives have attracted increasing attention, and the studies on them are performing to enrich the chemistry of carbon. Density functional theory calculations are performed on nonclassical fullerenes C(n) (n = 46, 48, 50, and 52) to give insight into their structures and stability. The calculated results demonstrate that the classical isomers generally satisfy the pentagon adjacency penalty rule. However, the nonclassical isomers with a heptagon are more energetically favorable than the classical ones with the same number of pentagon-pentagon bonds (B(55) bonds), and many of them are even more stable than some classical isomers with fewer B(55) bonds. The nonclassical isomers with the lowest energy are higher in energy than the classical ones with the lowest energy, because they have more B(55) bonds. Generally, the HOMO-LUMO gaps of the former are larger than those of the latter. The sphericity and asphericity are unable to rationalize the unique stability of the nonclassical fullerenes with a heptagon. The pyramidization angles of the vertices shared by two pentagons and one heptagon are smaller than those of the vertices shared by two pentagons and one hexagon. It is concluded that the strain in the fused pentagons can be released by the adjacent heptagons partly, and consequently, it is a common phenomenon for nonclassical fullerenes to violate the pentagon adjacent penalty rule. These findings are heuristic and conducive to search energetically favorable isomers of C(n), especially as n is 62, 64, 66, and 68, respectively.


[Non septic, surgical complications and their treatment of acute necrotizing pancreatitis in 131 cases].
The authors analyse non septic, surgical complications and their treatment in 131 patients with acute necrotizing pancreatitis. Bleeding occurred in 13 patients 16 times. There were 3 cases with large intestine perforation, small intestine perforation twice in one patient and hydrothorax in 12 patients. The patients APACHE-II score was in the range of 15, 5, which was quite high. They experienced complications such as bleeding and bowel perforations mostly in those who underwent several reoperations. For the bleeding from acute duodenal ulcer conservative and surgical therapy (suturing) was executed. In the cases of intraabdominal bleeding they used several options such as, ligature, collagen mesh, Surgicell net and tamponation. Large intestine perforations were surgically treated with Hartmann's procedure or loop colostomy. The small intestine perforation was simply sutured. From the 12 patients with hydrothorax 8 underwent thoracic drainage. We lost 7 patients with bleeding, 3 with bowel perforations and 2 with hydrothorax. The authors believe that complications during therapy of acute necrotizing pancreatitis are high risk factor, but their treatment is not hopeless.


Human Papillomaviruses as Infectious Agents in Gynecological Cancers. Oncogenic Properties of Viral Proteins.
Human papillomaviruses (HPVs), which belong to the Papillomaviridae family, constitute a group of small nonenveloped double-stranded DNA viruses. HPV has a small genome that only encodes a few proteins, and it is also responsible for 5% of all human cancers, including cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers. HPV types may be classified as high- and low-risk genotypes (HR-HPVs and LR-HPVs, respectively) according to their oncogenic potential. HR-HPV 16 and 18 are the most common types worldwide and are the primary types that are responsible for most HPV-related cancers. The activity of the viral E6 and E7 oncoproteins, which interfere with critical cell cycle points such as suppressive tumor protein p53 (p53) and retinoblastoma protein (pRB), is the major contributor to HPV-induced neoplastic initiation and progression of carcinogenesis. In addition, the E5 protein might also play a significant role in tumorigenesis. The role of HPV in the pathogenesis of gynecological cancers is still not fully understood, which indicates a wide spectrum of potential research areas. This review focuses on HPV biology, the distribution of HPVs in gynecological cancers, the properties of viral oncoproteins, and the molecular mechanisms of carcinogenesis.


[Participation, sharing, communication: a compatence based on culture not on professional skills].
The increasing emphasis on the importance of a more direct and active role of citizen and patients not only in the processes of care, but more broadly in the definition of goals and in the formulation of health choices, can be considered one of the most interesting trends in medicine and society. There is also a consensus on the need that nurses should have a protagonist role in this scenario. The hypothesis which has guided the selection and the development of the topics of this dossier is specifically discussed in the Editorial: the quality and the yield of participation do not depend on "another" skill which could be thaught, but on the openess-readiness of the health care personnel to a lay listening, understanding, sharing of the background culture, voices, needs of the cultural contexts and of the variability of individuals and of poprilations. The different contributions have two complementary objectives: a) to outline what could be the overall philosophy and the main components of a culture of a non directive communication, b) to document with model cases how broad and stimulating on one side is the challenge, and on the other the richness of opportunities. Along the varions contributions it is stressed that: This is an area at risk of being dominated by conceptualizations and declarations of intents, while its credibility and contribution are strictly dependent on the robustness of experiences; Nurses must consider this area as a specifically important field of research, with strategies and tools which must be tailored to the specificity of the situations where participation-communication are considered a priority.


Binding of citreoviridin to human serum albumin: multispectroscopic and molecular docking.
Citreoviridin (CIT), a mycotoxin produced by Penicillium citreonigrum, is a common contaminant of wide range of agriproducts and detrimental to human and animal health. In this study, the interaction of CIT with human serum albumin (HSA) is researched by steady-state fluorescence, ultraviolet-visible (UV-Vis) absorption, circular dichroism (CD) methods, and molecular modeling. The association constants, binding site numbers, and corresponding thermodynamic parameters are used to investigate the quenching mechanism. The alternations of HSA secondary structure in the presence of CIT are demonstrated with UV-Vis, synchronous fluorescence, and CD spectra. The molecular modeling results reveal that CIT can bind with hydrophobic pocket of HSA with hydrophobic and hydrogen bond force. Moreover, an apparent distance of 3.25 nm between Trp214 and CIT is obtained via fluorescence resonance energy transfer method.


Transureteroureterostomy revisited: long-term surgical outcomes.
Transureteroureterostomy is a treatment alternative for ureteral obstruction when more conventionally reconstructive techniques are not feasible. We report on long-term outcomes of patients treated with transureteroureterostomy. A retrospective chart review of all patients treated with transureteroureterostomy from January of 1985 to February of 2007 was performed. We identified 63 patients who underwent transureteroureterostomy at our institution. Average treatment age was 31.5 years (range 1 to 83). Transureteroureterostomy was performed for 21 (33%) malignant and 42 (67%) benign indications. Reconstructions were 30 right-to-left (47.6%) and 33 left-to-right (52.4%) with 21 concurrent urinary diversions. There were 16 patients (25.4%) who received radiation before transureteroureterostomy. Postoperative complications occurred in 15 (23.8%) patients and were more common in those undergoing diversion for malignancy. Mean followup was 5.8 years (range 0.1 to 22.2) and 5 patients were lost to followup. Of the 56 patients with followup imaging the transureteroureterostomy was patent in 54 (96.4%) and obstructed in 2 (3.6%). Mean preoperative and recent calculated glomerular filtration rate for this cohort were 62.8 (range 13 to 154) and 71.8 (range 22 to 141) ml per minute, respectively (p = 0.04). Stone disease developed in 8 patients, and was treated with percutaneous nephrolithotomy (2), spontaneous passage (2), ureteroscopy (1) and surveillance (3). Subsequent urological intervention was required for obstruction or revision in 6 (10.3%) patients. We demonstrated the long-term safety and effectiveness of transureteroureterostomy with sustained improvement of renal function compared to preoperative status. Recurrent stricture, distal obstruction and stone disease occur in a small percentage of patients, and can be treated in most with minimal intervention.


Analysis of components and study on antioxidant and antimicrobial activities of oil in apple seeds.
In order to improve the comprehensive utilization of major by-products in apple-juice processing, the components, antioxidant and antimicrobial activities of oil in two species apple seeds, Fuji and New Red Star, were investigated. The Soxhlet extracted oil content of apple seeds raged from 20.69 to 24.32 g/100 g. The protein, fiber and ash contents were found to be 38.85-49.55 g/100 g, 3.92-4.32 g/100 g and 4.31-5.20 g/100 g, respectively; the extracted oils exhibited an iodine value of 94.14-101.15 g I/100 g oil; refractive index (40 degrees C) was 1.465-1.466; density (25 degrees C) was 0.902-0.903 mg/ml; saponification value was 179.01-197.25 mg KOH/g oil; and the acid value was 4.036-4.323 mg KOH/g oil. The apple seed oils mainly consisted of linoleic acid (50.7-51.4 g/100 g) and oleic acid (37.49-38.55 g/100 g). Other prominent fatty acids were palmitic acid (6.51-6.60 g/100 g), stearic acid (1.75-1.96 g/100 g) and arachidic acid (1.49-1.54 g/100 g). Apple seed oil was proven to possess interesting properties, emerging from its chemical composition and from the evaluation of its in vitro biological activities. The apple seed oil was almost completely active against bacteria, mildews were less sensitive to apple seed oil than yeasts, and the minimum inhibitory concentration (MIC) of apple seed oil ranged from 0.3 to 0.6 mg/ml. The observed biological activities showed that the oil had a good potential for use in the food industry and pharmacy.


Glycoproteome profiling of transforming growth factor-beta (TGFbeta) signaling: nonglycosylated cell death-inducing DFF-like effector A inhibits TGFbeta1-dependent apoptosis.
Transforming growth factor-beta (TGFbeta) is a potent regulator of cell growth, differentiation, and apoptosis. TGFbeta binds to specific serine/threonine kinase receptors, which leads to activation of Smad-dependent and Smad-independent signaling pathways. O-Glycosylation is a dynamic PTM which has been observed in many regulatory proteins, but has not been studied in the context of TGFbeta signaling. To explore the effect of TGFbeta1 on protein O-glycosylation in human breast epithelial cells, we performed analyses of proteins which were affinity purified with Helix pomatia agglutinin (HPA). HPA lectin allowed enrichment of proteins containing GalNAc and GlcNAc linked to serine and threonine residues. Using 2-DE and MALDI-TOF-MS, we identified 21 HPA-precipitated proteins, which were affected by treatment of cells with TGFbeta1. Among these proteins, regulators of cell survival, apoptosis, trafficking, and RNA processing were identified. We found that TGFbeta1 inhibited the appearance of cell death-inducing DFF-like effector A (CIDE-A) in 2-D gels with HPA-precipitated proteins. CIDE-A is a cell death activator which promotes DNA fragmentation. We observed that TGFbeta1 did not affect expression of CIDE-A, but inhibited its glycosylation. We found that deglycosylation of CIDE-A correlated with enhanced nuclear export of the protein, and that high level of nonglycosylated CIDE-A inhibited TGFbeta1-dependent cell death. Thus, inhibition of the glycosylation of CIDE-A may be a mechanism to protect cells from apoptosis.


Pharmacoeconomics of Helicobacter pylori: eradication versus maintenance therapy in controlling peptic ulcer disease.
We performed an electronic search in Medline and EMBASE for papers comparing Helicobacter pylori eradication and H(2)RA-maintenance therapy in peptic ulcer. Treatment to eradicate H. pylori in patients with a proven ulcer has a favorable cost-effectiveness compared with maintenance therapy, with benefits for the patient and society. In most studies, it was assumed that no more gastrointestinal drugs were needed after eradication. Additional research is needed to provide empirical evidence on gastrointestinal drug utilization after eradication of H. pylori. The development of a vaccine against H. pylori remains however the ultimate goal in the fight against peptic ulcer disease.


Bone Metastasis Initiation Is Coupled with Bone Remodeling through Osteogenic Differentiation of NG2+ Cells.
The bone microenvironment is dynamic and undergoes remodeling in normal and pathologic conditions. Whether such remodeling affects disseminated tumor cells (DTC) and bone metastasis remains poorly understood. Here, we demonstrated that pathologic fractures increase metastatic colonization around the injury. NG2+ cells are a common participant in bone metastasis initiation and bone remodeling in both homeostatic and fractured conditions. NG2+ bone mesenchymal stem/stromal cells (BMSC) often colocalize with DTCs in the perivascular niche. Both DTCs and NG2+ BMSCs are recruited to remodeling sites. Ablation of NG2+ lineage impaired bone remodeling and concurrently diminished metastatic colonization. In cocultures, NG2+ BMSCs, especially when undergoing osteodifferentiation, enhanced cancer cell proliferation and migration. Knockout of N-cadherin in NG2+ cells abolished these effects in vitro and phenocopied NG2+ lineage depletion in vivo. These findings uncover dual roles of NG2+ cells in metastasis and remodeling and indicate that osteodifferentiation of BMSCs promotes metastasis initiation via N-cadherin-mediated cell-cell interaction. The bone colonization of cancer cells occurs in an environment that undergoes constant remodeling. Our study provides mechanistic insights into how bone homeostasis and pathologic repair lead to the outgrowth of disseminated cancer cells, thereby opening new directions for further etiologic and epidemiologic studies of tumor recurrences. This article is highlighted in the In This Issue feature, p. 247.


Global uptake of the Humanitarian Accountability Partnership over its first ten years.
Accountability in the delivery of humanitarian aid has become increasingly important and emphasized by the humanitarian community. The Humanitarian Accountability Partnership (HAP) was created in 2003 in order to improve accountability in the humanitarian sector. HAP acts as a self-regulatory body to the humanitarian system. One of the main goals of HAP is the promotion of accountability through self-regulation by members. Humanitarian nongovernmental organizations (NGOs) can become members by meeting standards of accountability and quality management set by HAP. This report describes the growth of HAP membership by the humanitarian community from its inception until present. Hypothesis/Problem The hypothesis for this study was that HAP membership has grown substantially since inception, both in terms of number of member organizations and annual budgets of member organizations, but that near universal membership has not yet been achieved. A retrospective study was conducted to determine the total number and percentage of humanitarian NGOs that are members of HAP. Total expenditures of HAP members in 2010 also was measured and compared with the total humanitarian expenditure by all humanitarian NGOs for the same year. The reference year of 2010 was chosen in order to be able to compile accurate budgets for the largest possible number of HAP members. The total number of HAP members for the years 2005 through 2012 was divided by the estimated number of humanitarian NGOs active in 2010. The total budgets for HAP members in 2010 were divided by the estimated total humanitarian expenditure of all NGOs for 2010. As of the beginning of 2012, the percentage of humanitarian NGOs that were members of HAP was 1.6% (68 members out of 4400 organizations). The combined budgets of the member organizations of HAP in 2010 made up 62.9% of the total humanitarian expenditure for the year 2010 (US $4.65 billion/7.4 billion). A very small proportion of humanitarian NGOs have adopted HAP membership. However, HAP members account for almost two-thirds of all humanitarian expenditures. The humanitarian sector, therefore, remains without a universal regulatory and accountability structure, although progress has been made. Efforts should be made to increase the membership within HAP of more small to medium sized organizations.


Atomistic Simulations of Functionalized Nano-Materials for Biosensors Applications.
Nanoscale biosensors, a highly promising technique in clinical analysis, can provide sensitive yet label-free detection of biomolecules. The spatial and chemical specificity of the surface coverage, the proper immobilization of the bioreceptor as well as the underlying interfacial phenomena are crucial elements for optimizing the performance of a biosensor. Due to experimental limitations at the microscopic level, integrated cross-disciplinary approaches that combine in silico design with experimental measurements have the potential to present a powerful new paradigm that tackles the issue of developing novel biosensors. In some cases, computational studies can be seen as alternative approaches to assess the microscopic working mechanisms of biosensors. Nonetheless, the complex architecture of a biosensor, associated with the collective contribution from "substrate-receptor-analyte" conjugate in a solvent, often requires extensive atomistic simulations and systems of prohibitive size which need to be addressed. In silico studies of functionalized surfaces also require ad hoc force field parameterization, as existing force fields for biomolecules are usually unable to correctly describe the biomolecule/surface interface. Thus, the computational studies in this field are limited to date. In this review, we aim to introduce fundamental principles that govern the absorption of biomolecules onto functionalized nanomaterials and to report state-of-the-art computational strategies to rationally design nanoscale biosensors. A detailed account of available in silico strategies used to drive and/or optimize the synthesis of functionalized nanomaterials for biosensing will be presented. The insights will not only stimulate the field to rationally design functionalized nanomaterials with improved biosensing performance but also foster research on the required functionalization to improve biomolecule-surface complex formation as a whole.


The Genomic Architecture of Pregnancy-Associated Plasticity in the Maternal Mouse Hippocampus.
Pregnancy is associated with extraordinary plasticity in the maternal brain. Studies in humans and other mammals suggest extensive structural and functional remodeling of the female brain during and after pregnancy. However, we understand remarkably little about the molecular underpinnings of this natural phenomenon. To gain insight into pregnancy-associated hippocampal plasticity, we performed single nucleus RNA sequencing (snRNA-seq) and snATAC-seq from the mouse hippocampus before, during, and after pregnancy. We identified cell type-specific transcriptional and epigenetic signatures associated with pregnancy and postpartum adaptation. In addition, we analyzed receptor-ligand interactions and transcription factor (TF) motifs that inform hippocampal cell type identity and provide evidence of pregnancy-associated adaption. In total, these data provide a unique resource of coupled transcriptional and epigenetic data across a dynamic time period in the mouse hippocampus and suggest opportunities for functional interrogation of hormone-mediated plasticity.


The variation in free 25-hydroxy vitamin D and vitamin D-binding protein with season and vitamin D status.
Serum 25-hydroxy vitamin D [25(OH)D] varies greatly with season at northern latitudes. The purpose of this study was to determine if the seasonal variations in serum total 25(OH)D are followed by a concomitant variation in free 25(OH)D or if the variation is damped by alterations in the binding capacity of DBP. Serum was collected from 540 healthy blood donors (60% men; mean age 41 ± 13 years) during 12 months and analyzed for total 25(OH)D, directly measured free 25(OH)D, vitamin D-binding protein (DBP) and albumin. Calculated free 25(OH)D was estimated. The UV-B radiation during the sampling month was positively correlated with the serum levels of total 25(OH)D (r = 0.355, P < 0.001), directly measured free (r = 0.336, P < 0.001) and calculated free 25(OH)D (r = 0.275, P < 0.001), but not with DBP and albumin. The percentage of free 25(OH)D was higher during the winter months than that during the summer months (0.020 ± 0.005% vs 0.019 ± 0.004%; P = 0.007) and higher in participants with a serum 25(OH)D below 25 nmol/L than that in participants with a serum 25(OH)D above 75 nmol/L (0.031 ± 0.007% vs 0.017 ± 0.003%; P < 0.001). iPTH was correlated with directly measured free 25(OH)D (r = -0.226; P < 0.001), but only weakly with calculated free 25(OH)D (r = -0.095; P = 0.027). Directly measured free serum 25(OH)D was highly correlated with total serum 25(OH)D and followed the same seasonal variation, whereas the serum concentrations of DBP and albumin were stable. The fluctuation in free 25(OH)D was only marginally damped with an increase in the percentage of free 25(OH)D during the winter months and in participants with vitamin D deficiency.


An overview on benzylisoquinoline derivatives with dopaminergic and serotonergic activities.
Dopamine and serotonin are important neurotransmitters in the mammalian central nervous system (CNS) involved in numerous physiological and behavioural disorders such as schizophrenia, major depression, anxiety, Parkinson's and Huntington's diseases, and attention deficit hyperactivity disorder. Several natural and synthetic benzylisoquinoline derivatives have displayed affinity for dopamine and serotonin receptors in nanomolar or micromolar ranges. This review covers the last three decades of dopaminergic and serotonergic activities, and especially focuses on structure-activity relationships of natural and synthetic benzylisoquinoline derivatives. We have included aporphines, 1-benzyltetrahydroisoquinolines, bis-benzylisoquinolines, protoberberines, cularines and other structural analogues. Further molecular modelling calculations have been considered as important tools to not only obtain structural information of both neurotransmitter receptors, but to also identify their pharmacophore features. The development of selective potential ligands like benzylisoquinoline derivatives may help in the therapy of diseases related to CNS dysfunction.


Preference-Aligned Fertility Management as a Person-Centered Alternative to Contraceptive Use-Focused Measures.
Equating contraceptive use with programmatic success is fundamentally flawed in failing to account for whether individuals desire contraceptive use; this is problematic because nonuse can reflect empowered decision-making and use may reflect an individual's inability to refuse or discontinue a method. A rights-based approach demands respect for individuals' freedom to weigh options and choose how their desire for pregnancy prevention can be accommodated by available methods and within the context of their own personal, social, and material constraints. We offer an alternative construct, preference-aligned fertility management (PFM), that provides a more holistic indicator of whether one's contraceptive needs are met. PFM is more person-centered and informative for programming than status quo measures of unmet need, demand satisfied, and contraceptive use which define a positive outcome in relation to pregnancy risk rather than one's stated preferences. The PFM approach goes beyond other recent proposals for modifying the concept of unmet need by refraining from judgment of legitimate reasons for nonuse of contraception and offers a straightforward way to capture whether people act in line with their preferences. We conclude with discussion of how we plan to measure PFM in the Innovations for Choice and Autonomy (ICAN) study in Nigeria and Uganda.


Four Gaucher disease type II patients with three novel mutations: a single centre experience from Turkey.
Gaucher disease is the most common lysosomal storage disorder due to glucosylceramidase enzyme deficiency. There are three subtypes of the disease. Neurological involvement accompanies visceral and haematological findings only in type II and type III Gaucher patients. Type II is the acute progressive neuronopathic form which is the most severe and rare subtype. Clinical findings are recognized prenatally or in the first months of life and followed by death within the first two years of age. Among our 81 Gaucher patients, we identified 4 (4,9%) type II patients in our metabolic centre. This rate is significantly higher than the rate reported in the literature (<1%). Three of the patients had novel mutations, one of them was a collodion baby and the other one was mistyped as type III due to its atypical presentation at the beginning and he was treated with ERT for 8 months. In this report, we present our type II Gaucher patients with three novel mutations and one perinatal lethal form with generalized ichthyosis which is a very rare disorder. Additionally, we would like to highlight the phenotypic heterogeneity not only between the subtypes, also even in the same type.


Environmental exposure to polychlorinated biphenyls and breast cancer risk.
Breast cancer is a major public health problem in the United States and in most industrialized countries. Although epidemiologic studies have identified a number of established risk factors for this disease, these factors explain only a small proportion of breast cancer incidence. Environmental exposure has been implicated in breast cancer etiology because of the vast geographic variation in breast cancer incidence rates across countries and regions within countries. Further, the steady increase in breast cancer rates over the past decades points to a potential role of environmental exposure in its development. One suspected environmental factor is the polychlorinated biphenyls (PCBs), which were manufactured commercially for a variety of industrial applications from the 1930s until the 1970s. PCBs have been associated with estrogenic, tumor promoting, and immunosuppressive activities, all of which are relevant in the development of breast cancer. The purpose of this review is to summarize the growing body of epidemiological evidence on the association between environmental PCB exposure and breast cancer risk. Three major types of study design have been used to investigate such a relation: clinic-based case-control studies, retrospective case-control studies, and nested case-control studies. Although findings from clinic-based case-control studies tend to point to an adverse effect of high PCB body burden on risk, the results from the more methodologically sound retrospective and nested studies do not provide strong support for a role of PCBs in breast cancer development. The association between PCB exposure and risk among racially and genetically susceptible subgroups may warrant further investigation. Methodological challenges in the design and analysis of epidemiologic studies on PCBs and breast cancer risk are discussed.


Ahmed Hankir: fighting mental health stigma.
Ahmed Hankir talks to Vijay Shankar Balakrishnan about his work at the frontier between the arts and clinical psychiatry to combat stigma.


Association of Prior Intracerebral Hemorrhage With Major Adverse Cardiovascular Events.
Patients with stroke due to nontraumatic (spontaneous) intracerebral hemorrhage (ICH) often harbor vascular risk factors and comorbidities, but it is unclear which major adverse cardiovascular events (MACEs) occur more frequently among patients with a prior ICH than the general population. To evaluate the risk of a MACE for patients with a prior ICH compared with the general population. This cohort study identified 8991 patients with a first ICH in the Danish Stroke Registry from January 1, 2005, to June 30, 2018, who were aged 45 years or older and survived more than 30 days after an ICH. Patients in this ICH cohort were matched 1:40 on age, sex, and ICH-onset date with a comparison cohort of 359 185 individuals from the general population without a prior ICH. Both cohorts were followed up for 6 months or more until December 31, 2018, for outcomes using registry data. Data were analyzed from October 1, 2021, to July 19, 2022. Intracerebral hemorrhage identified by a nationwide clinical database. The main outcomes were ICH, ischemic stroke, myocardial infarction, and a composite of MACEs. For each outcome, a case-control study nested within the cohorts was also performed, adjusting for time-varying exposures and potential confounders. Crude absolute event rates per 100 person-years, adjusted hazard ratios (aHRs) and 95% CIs and, in the nested case-control analyses, crude and adjusted odds ratios and 95% CIs were calculated. The ICH cohort (n = 8991; 4814 men [53.5%]; mean [SD] age, 70.7 [11.5] years) had higher event rates than the comparison cohort (n = 359 185; 192 256 men [53.5%]; mean [SD] age, 70.7 [11.5] years) for MACEs (4.16 [95% CI, 3.96-4.37] per 100 person-years vs 1.35 [95% CI, 1.33-1.36] per 100 person-years; aHR, 3.13 [95% CI, 2.97-3.30]), ischemic stroke (1.52 [95% CI, 1.40-1.65] per 100 person-years vs 0.56 [95% CI, 0.55-0.57] per 100 person-years; aHR, 2.64 [95% CI, 2.43-2.88]), and ICH (1.44 [95% CI, 1.32-1.56] per 100 person-years vs 0.06 [95% CI, 0.06-0.07] per 100 person-years; aHR, 23.49 [95% CI, 21.12-26.13]) but not myocardial infarction (0.52 [95% CI, 0.45-0.60] per 100 person-years vs 0.48 [95% CI, 0.47-0.49] per 100 person-years; aHR, 1.12 [95% CI, 0.97-1.29]). Nested case-control analyses returned risk estimates of similar magnitude as the cohort analyses. The findings of this cohort study suggest that Danish patients with a prior ICH had statistically significantly higher rates of MACEs than the general population, indicating a need for attention to optimal secondary prevention with blood pressure lowering and antithrombotic and statin therapies after an ICH in clinical research and practice.


Control of Tissue Reactions in Monkeys Vaccinated with Viable Coccidioides immitis by Prevaccination with Killed Coccidioides immitis.
Converse, J. L. (U.S. Army Biological Laboratories, Fort Detrick, Frederick, Md.), G. A. Deauville, E. M. Snyder, J. G. Ray, and M. E. Seaquist. Control of tissue reactions in monkeys vaccinated with viable Coccidioides immitis by prevaccination with killed Coccidioides immities. J. Bacteriol. 90:783-788. 1965.-Control of undesirable tissue reactions resulting from the subcutaneous injection of 150 viable arthrospores of Coccidioides immitis (strain D-76) was obtained by four injections of formalin-killed arthrospores 14, 12, 8, and 4 weeks (total dose, 36 mg) before injection of the viable arthrospores. Only 6 and 12% of these vaccinated animals exhibited ulceration and lymphadenopathy, respectively, as compared with 100 and 83% of the animals receiving only the viable vaccine. Agar-gel immunodiffusion precipitin titers of approximately 1:64 were evident 3 months after vaccination in animals receiving both vaccines, as compared with 1:128 in those injected with the viable vaccine alone. The above data indicated that somatic reactions to injection of a viable vaccine could be eliminated by preinjection of a killed vaccine. However, 6 months after vaccination, respiratory challenge (7,500 strain Cash arthrospores) indicated that this treatment also impaired the protective effect of the viable vaccine. All animals receiving both vaccines developed mild pulmonary coccidioidomycosis, whereas only 50% of the animals receiving only the viable vaccine were infected. In addition, the group receiving both vaccines demonstrated a more rapid and higher postchallenge precipitin titer. All vaccinated animals (those receiving the killed, the viable, or a combination of the two vaccines) survived for 4 months after challenge, as compared with 88% mortality (50% within 14 days) in the nonvaccinated controls.


Free-energy based pair-additive potentials for bulk Ni-Al systems: application to study Ni-Al reactive alloying.
We present new numerical pair-additive Al, Ni, and Al-Ni potentials by force-matching (FM) ionic force and virial data from single (bulk liquid) phase ab initio molecular dynamics (MD) simulations using the Born-Oppenheimer method. The potentials are represented by piece-wise functions (splines) and, therefore, are not constrained to a particular choice of analytical functional form. The FM method with virial constraint naturally yields a potential which maps out the ionic free-energy surface of the reference ensemble. To further improve the free energetics of the FM ensemble, the FM procedure is modified to bias the potentials to reproduce the experimental melting temperatures of the reference (FCC-Al, FCC-Ni, B2-NiAl) phases, the only macroscopic data included in the fitting set. The performance of the resultant potentials in simulating bulk metallic phases is then evaluated. The new model is applied to perform MD simulations of self-propagating exothermic reaction in Ni-Al bilayers at P = 0-5 GPa initiated at T = 1300 K. Consistent with experimental observations, the new model describes realistically a sequence of peritectic phase transformations throughout the reaction and at a realistic rate. The reaction proceeds through interlayer diffusion of Al and Ni atoms at the interface with formation of B2-NiAl in the Al melt. Such material responses have, in the past, been proven to be difficult to observe with then-existing potentials.


Exceptionally aggressive pigmented villonodular synovitis of the hip unresponsive to radiotherapy.
Pigmented villonodular synovitis (PVNS) is a rare benign neoplastic proliferation of synovial tissue which is typically localised and usually responds well to surgery and/or radiotherapy. We present a case of unusually aggressive of PVNS of the hip in a 73-year-old woman.


[Regional myocardial contraction in ischemic heart disease: evaluation of regional myocardial thickening by two-dimensional echocardiography].
There were many studies concerning the evaluation of regional wall motion in ischemic heart disease by left ventriculography (LVG) and two-dimensional echocardiography (2DE), but only a few observations on the regional myocardial thickening have been reported. In a survey of 48 cases of old myocardial infarction, we selected 21 cases with adequate 2DE images for the evaluation of regional wall motion and thickening. In all cases the 2DE examinations were performed within seven days before or after LVG examinations. The left ventricular wall on 2DE was divided into 11 segments and wall motion and thickening in each segment were graded to three classes, i.e. none, reduced and normal. The results on 2DE were then compared with the grade of wall motion of the corresponding segment on LVG. The sensitivity and specificity of 2DE wall motion were 50% and 89% in none, 59% and 48% in reduced, and 89% and 84% in normal, respectively. The sensitivity and specificity of 2DE myocardial thickening were 81% and 93% in none, 82% and 70% in reduced, and 92% in normal, respectively. These results indicated that the regional myocardial thickening by 2DE has a higher sensitivity and specificity. Therefore, observation of both myocardial thickening and wall motion will be necessary for the proper evaluation of regional myocardial contraction in ischemic heart disease.


Sympathetic neural inhibition of conducted vasodilatation along hamster feed arteries: complementary effects of alpha1- and alpha2-adrenoreceptor activation.
Vasodilatation initiated on arterioles of skeletal muscle ascends into the proximal feed arteries through cell-to-cell conduction along the endothelium and into smooth muscle. Whereas perivascular sympathetic nerve activity (SNA) can inhibit conducted vasodilatation and restrict muscle blood flow, the signalling events mediating this interaction are poorly defined. Therefore, using isolated pressurized (75 mmHg) feed arteries (diameter (microm) at rest = 53 +/- 3; maximum = 99 +/- 2; n = 86) of the hamster retractor muscle, we tested the hypothesis that distinct yet complementary signalling pathways underlie the ability of SNA to inhibit conduction. Conducted vasodilatation was initiated using ACh microiontophoresis (1 microA; 250, 500 and 1000 ms) and SNA was initiated using local field stimulation (30-50 V; 1 ms at 2, 8 and 16 Hz). With vasodilatations of 5-20 microM, conduction increased with ACh pulse duration and was inhibited progressively as the frequency of SNA increased. During SNA, conduction was partially restored with inhibition of alpha1- (0.1 microM prazosin) or alpha2- (0.1 microM RX821002) adrenoreceptors and fully restored with both antagonists present. Activating alpha1- (50 nM phenylephrine) or alpha2- (1 microM UK 14,304) adrenoreceptors inhibited conduction partially and their simultaneous activation inhibited conduction cumulatively (P < 0.05). Elevated [K+]o (30 or 40 mM) or phorbol esters (0.5 microM) also inhibited conduction yet similar constriction with l-NNA (50 microM) or Bay K 8644 (10 nM) did not. Thus, the activation of alpha1- and alpha2-adrenoreceptors inhibits conducted vasodilatation through complementary signalling events. With robust coupling along the endothelium, our modelling predicts that the inhibition of conduction by SNA can be explained by reduced electrical coupling through myoendothelial gap junctions or greater current leak across smooth muscle cell membranes.


Proposed protocol for the investigation of the safety and efficacy of the COVID-19 vaccine for patients with psychosis, with pilot safety findings from a Chinese psychiatrist's self-experiment.
We present a study protocol designed to test the safety and efficacy of the 2019 coronavirus disease (COVID-19) vaccine in patients with major psychotic disease. A secondary objective is to investigate optional vaccination methods for these patients. In a self-experiment, a Chinese psychiatrist examined the safety and efficacy of the COVID-19 vaccine under clinical use of typical antipsychotic agents and sedatives (olanzapine, duloxetine, and diazepam). For patients with extremely drug-resistant conditions, the safety of the COVID-19 vaccine under electroconvulsive therapy was also investigated. The entire study process was recorded on high-definition video. This clinical study protocol is, to our knowledge, the first of its kind. Our findings will shed new light on the protection of patients with psychotic diseases from COVID-19 infection. The protocol was registered at Chinese clinical trial registry (www.chictr.org.cn, ChiCTR2100051297).


Adipose tissues differentiated by adipose-derived stem cells harvested from transgenic mice.
To induce adipocyte differentiation in vitro by adipose-derived stromal cells (ASCs) harvested from transgenic mice with green fluorescent protein (GFP)and assess the possibility of constructing adipose tissues via attachment of ASCs to type I collagen scaffolds. Inguinal fat pads from GFP transgenic mice were digested by enzymes for isolation of ASCs (primary culture). After expansion to three passages of ASCs, the cells were incubated in an adipogenic medium for two weeks, and the adipocyte differentiation by ASCs in vitro was assessed by morphological observation and Oil Red O staining. Then they were attached to collagen scaffolds and co-cultured for 12 hours, followed by hypodermic implantation to the dorsal skin of nude mice for 2 months. The newly-formed tissues were detected by HE staining. The cultured primary stem cells were fibroblast-like and showed active proliferation. After being incubated in an adipocyte differentiation medium, the lipid droplets in the cytoplasm accumulated gradually and finally developed into mature adipocytes, which showed positive in Oil Red O staining. A 0.5-cm3 new tissue clot was found under the dorsal skin of the nude mice and it was confirmed as mature adipose tissues by fluorescent observation and HE staining. ASCs can successfully differentiate adipose tissues into mature adipocytes, which exhibit an adipocyte-like morphology and express as intracytoplasmic lipid droplets. It is an efficient model of adipose tissues engineered with ASCs and type I collagen scaffolds.


Study Progress on Inorganic Fibers from Industry Solid Wastes and the Key Factors Determining Their Characteristics.
Compared to basalt and glass fibers, the production of inorganic fiber from industry solid wastes is an effective method to not only save natural resources but also recycle waste resources. Because the preparation of the fibers requires high temperature treatment, the production process is associated with high energy consumption and high carbon emissions. How to resolve these problems is a current research challenge in this field. Herein, we reviewed the study progress on these fibers and further discussed the key factors determining their characteristics, including chemical composition, melt structure, and viscosity of melt. In production, the matching of solid waste blends containing enough total content of SiO2 and Al2O3, and a suitable amount of MgO and CaO, is beneficial to the structure control of the melt. The study found that the melt consisted of Q2 and Q3; and that Q3 content more than Q2 was more suitable for fiber production and its performance improvement. Such a melt structure can be achieved by controlling the degree of depolymerization and the temperature. New ultrasonic technology can shorten the homogenization time; its application is hoped to save energy and reduce carbon emissions. These conclusions will offer important guidance for the development of inorganic fibers from industry solid wastes in the future.


Long working hours, sedentary work, noise, night shifts and risk of ischaemic heart disease.
Ischaemic heart disease (IHD) is a leading cause of death in Western countries. The aim of this study was to examine the associations between occupational exposure to loud noise, long working hours, shift work, and sedentary work and IHD. This data linkage study included all New Zealanders employed and aged 20-64 years at the time of the 2013 census, followed up for incident IHD between 2013 and 2018 based on hospitalisation, prescription and death records. Occupation and number of working hours were obtained from the census, and exposure to sedentary work, loud noise and night shift work was assessed using New Zealand job exposure matrices. HRs were calculated for males and females using Cox regression adjusted for age, socioeconomic status, smoking and ethnicity. From the 8 11 470 males and 7 83 207 females employed at the time of the census, 15 012 male (1.9%) and 5595 female IHD cases (0.7%) were identified. For males, there was a modestly higher risk of IHD for the highest category (>90 dBA) of noise exposure (HR 1.19; 95% CI 1.07 to 1.33), while for females exposure prevalence was too low to calculate an HR. Night shift work was associated with IHD for males (HR 1.10; 95% CI 1.05 to 1.14) and females (HR 1.25; 95% CI 1.17 to 1.34). The population attributable fractions for night shift work were 1.8% and 4.6%, respectively. No clear associations with working long hours and sedentary work were observed. This study suggests that occupational exposures to high levels of noise and night shift work might be associated with IHD risk.


Three-component tandem reaction involving acid chlorides, terminal alkynes, and 2-aminoindole hydrochlorides: synthesis of α-carboline derivatives in aqueous conditions via regioselective [3 + 3] cyclocondensation.
An efficient synthesis toward highly diversified α-carboline derivatives via a three-component tandem reaction using acid chlorides, terminal alkynes, and 2-aminoindole hydrochlorides has been described. The salient feature of the one-pot strategy involves regioselective [3 + 3]-cyclocondensation and the presence of water in the reaction medium to facilitate cyclization. Nonaqueous conditions furnished products in poor yields.


Type I Jejunal Atresia in Identical Twins: A Rare Occurrence.
Jejunoileal atresia is of familial and non-familial in origins and classified into four different types. We herein report a rare occurrence of type I jejunal atresia in identical twins who were presented with neonatal intestinal obstruction. This report points towards common etiology of atresia in our cases and factors more than vascular accident appear to be involved.


Delayed Small Bowel Incarceration Within a Lumbar Burst Fracture After Posterior Spinal Fusion: A Case Report.
We present a case report of a patient who had delayed small bowel obstruction secondary to an incarcerated loop of small bowel within an acute lumbar spine fracture. The patient was involved in a rollover motor vehicle accident, resulting in lumbar spine fractures at L2-4. A comminuted fracture of the L3 vertebral body with likely disruption of the anterior longitudinal ligament (ALL) was noted. The patient underwent L1-4 posterior spinal fusion with the introduction of mild lumbar lordosis to prevent future complications of flatback syndrome. On postoperative Day 4, the patient was noted to have signs and symptoms of progressive small bowel obstruction. Conservative management was initiated with minimal improvement. The patient was taken to the operating room on postoperative Day 7 for an exploratory laparotomy. A necrotic loop of small bowel was noted to be entrapped in the ventral L3 vertebral body defect. This bowel was released and resected, with side-to-side anastomosis performed. No previous cases describe small bowel incarceration because of posterior spinal fusion for trauma. The introduction of increased lumbar lordosis is thought to have contributed to this risk of small bowel herniation, and care must be taken when determining appropriate spinopelvic parameters in these cases.


Different rates of spontaneous mutation of chloroplastic and nuclear viroids as determined by high-fidelity ultra-deep sequencing.
Mutation rates vary by orders of magnitude across biological systems, being higher for simpler genomes. The simplest known genomes correspond to viroids, subviral plant replicons constituted by circular non-coding RNAs of few hundred bases. Previous work has revealed an extremely high mutation rate for chrysanthemum chlorotic mottle viroid, a chloroplast-replicating viroid. However, whether this is a general feature of viroids remains unclear. Here, we have used high-fidelity ultra-deep sequencing to determine the mutation rate in a common host (eggplant) of two viroids, each representative of one family: the chloroplastic eggplant latent viroid (ELVd, Avsunviroidae) and the nuclear potato spindle tuber viroid (PSTVd, Pospiviroidae). This revealed higher mutation frequencies in ELVd than in PSTVd, as well as marked differences in the types of mutations produced. Rates of spontaneous mutation, quantified in vivo using the lethal mutation method, ranged from 1/1000 to 1/800 for ELVd and from 1/7000 to 1/3800 for PSTVd depending on sequencing run. These results suggest that extremely high mutability is a common feature of chloroplastic viroids, whereas the mutation rates of PSTVd and potentially other nuclear viroids appear significantly lower and closer to those of some RNA viruses.


Soft phonon modes driven huge difference on lattice thermal conductivity between topological semimetal WC and WN.
Topological semimetals are currently attracting increasing interest due to their potential applications in topological qubits and low-power electronics, which are closely related to their thermal transport properties. Recently, the triply degenerate nodal points near the Fermi level of WC are observed by using angle-resolved photoemission spectroscopy. In this work, by solving the Boltzmann transport equation based on first-principles calculations, we systematically investigate the phonon transport properties of topological semimetals WC and WN. The predicted room-temperature lattice thermal conductivities of WC (WN) along the a and c directions are 1140.64 (7.47) W m-1 K-1 and 1214.69 (5.39) W m-1 K-1. Considering the similar crystal structure of WC and WN, it is quite interesting to find that the thermal conductivity of WC is more than two orders of magnitude higher than that of WN. It is found that, different from WN, the large acoustic-optical (a-o) gap prohibits the acoustic+acoustic → optical (aao) scattering, which gives rise to very long phonon lifetimes, leading to ultrahigh lattice thermal conductivity in WC. For WN, the lack of an a-o gap is due to soft phonon modes in optical branches, which can provide more scattering channels for aao scattering, producing very short phonon lifetimes. Further deep insight can be attained from their different electronic structures. Distinctly different from that in WC, the density of states of WN at the Fermi level becomes very sharp, which leads to destabilization of WN, producing soft phonon modes. It is found that the small shear modulus G and C44 limit the stability of WN, compared with WC. Our studies provide valuable information for phonon transports in WC and WN, and motivate further experimental studies to study their lattice thermal conductivities.


Potential workplace hazards to reproductive health. Information for primary prevention.
Each year in the United States, more than two million employed women become pregnant. Reproductive hazards in the workplace threaten a large number of these pregnancies. Information is presented on the potential hazards to reproductive health that exist in the workplace.


RDoC-based categorization of amygdala functions and its implications in autism.
Confusion endures as to the exact role of the amygdala in relation to autism. To help resolve this we turned to the NIMH's Research Domain Criteria (RDoC) which provides a classification schema that identifies different categories of behaviors that can turn pathologic in mental health disorders, e.g. autism. While RDoC incorporates all the known neurobiological substrates for each domain, this review will focus primarily on the amygdala. We first consider the amygdala from an anatomical, historical, and developmental perspective. Next, we examine the different domains and constructs of RDoC that the amygdala is involved in: Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Social Processes, and Arousal and Regulatory Systems. Then the evidence for a dysfunctional amygdala in autism is presented with a focus on alterations in development, prenatal valproic acid exposure as a model for ASD, and changes in the oxytocin system therein. Finally, a synthesis of RDoC, the amygdala, and autism is offered, emphasizing the task of disambiguation and suggestions for future research.


Implementing active surveillance for tuberculosis: The experiences of healthcare workers at four sites in two provinces in South Africa.
The high burden of tuberculosis (TB) in South Africa (SA) is associated with uncontrolled transmission in communities and delayed diagnosis of active cases. Active surveillance for TB is provided by community-based services (CBS). Research is required to understand key factors influencing TB screening services in the CBS. This study explored the implementation of active surveillance for TB where community-oriented primary care (COPC) had been successfully implemented to identify these factors. This was a qualitative study of four established COPC sites across two provinces in SA where active surveillance for TB is implemented. Semi-structured interviews were conducted with purposively selected healthcare workers in the CBS and citizens in these communities. The recorded interviews were transcribed for data analysis using ATLAS.ti software. The factors influencing active surveillance for TB were directly related to the major players in the delivery of CBS. These factors interacted in a complex network influencing implementation of active surveillance for TB. Building effective relationships across stakeholder platforms by community health workers (CHWs) was directly influenced by the training, capacity building afforded these CHWs by the district health services; and acceptability of CBS. Each factor interplayed with others to influence active surveillance for TB. Community health workers were central to the success of active surveillance for TB. The complex interactions of the social determinants of health and TB transmission in communities required CHWs to develop trusting relationships that responded to these issues that have impact on TB disease and linked clients to healthcare.


Mechanism of metal ion activation of the diphtheria toxin repressor DtxR.
The diphtheria toxin repressor (DtxR) is a metal ion-activated transcriptional regulator that has been linked to the virulence of Corynebacterium diphtheriae. Structure determination has shown that there are two metal ion binding sites per repressor monomer, and site-directed mutagenesis has demonstrated that binding site 2 (primary) is essential for recognition of the target DNA repressor, leaving the role of binding site 1 (ancillary) unclear. Calorimetric techniques have demonstrated that although binding site 1 (ancillary) has high affinity for metal ion with a binding constant of 2 x 10(-7), binding site 2 (primary) is a low-affinity binding site with a binding constant of 6.3 x 10(-4). These two binding sites act in an independent fashion, and their contribution can be easily dissected by traditional mutational analysis. Our results clearly demonstrate that binding site 1 (ancillary) is the first one to be occupied during metal ion activation, playing a critical role in stabilization of the repressor. In addition, structural data obtained for the mutants Ni-DtxR(H79A,C102D), reported here, and the previously reported DtxR(H79A) have allowed us to propose a mechanism of metal activation for DtxR.


[First case of lung abscess due to Yersinia pseudotuberculosis in Japan].
A 63-year-old previously healthy man was admitted to our hospital with diarrhea that had lasted for about 4 weeks, high fever and dyspnea. Chest computed tomography showed consolidation with a low-density area in the right middle lobe and small nodules with feeding vessels in the right upper lobe. On Day 8, a cavity was observed in the consolidation, and the lymph nodes in the mediastinum became necrotic. Yersinia pseudotuberculosis (serotype 4b) was cultured from blood, bronchial washing fluid, and lung tissue specimens. We diagnosed the lung lesions as septic pulmonary embolism caused by enterocolitis. We started treatment with tazobactam/piperacillin. It has been reported that high-dose ceftriaxone (CTRX) is effective, but CTRX at normal doses and other beta-lactams are less effective or even ineffective. Therefore, we changed to CTRX (4g/day) on Day 5, CTRX (2g/day) on Day 8, and oral cefditoren pivoxil (600 mg/day; a third-generation cephalosporin) on Day 18. Antibiotic therapy resulted in a favorable response. The patient was discharged from our hospital on day 25 in good health. To the best of our knowledge, this is the first case of a lung abscess caused by Y. pseudotuberculosis reported in Japan.


Commentary on 'Surface markers associated with chondrogenic potential of human mesenchymal stromal/stem cells'.
In the last decade, researchers have searched for predictive surface markers of multipotent mesenchymal stromal/stem cells (MSCs) for ensuring improved therapeutic outcomes following cartilage damage in humans. However, we have achieved only limited progress because of the challenge presented by conflicting data. This commentary provides some evidence to prove a lack of success with current efforts, including an inconsistency in accepted surface markers and chondrogenic potential of MSCs as well as the tissue source-dependent MSC surface markers that correlate with chondrogenic potential. A brief discussion on these disputed topics and perspective about functionally predictive surface markers and standardization of analytic procedures are also highlighted.


Group psychotherapy in acute treatment settings: theory and technique.
Group psychotherapy has long been a part of most inpatient and partial hospital programs, but conducting groups in these settings has become more difficult as the average patient stay has shortened. The authors integrate findings from previous research in which patients ranked the importance of several therapeutic processes in acute care groups, and they suggest a theory of group psychotherapy that incorporates realistic clinical objectives for these short-term settings. Seven therapeutic factors--self-responsibility, self-understanding, instillation of hope, group cohesiveness, catharsis, altruism, and universality--are identified as important in promoting patient change. Specific techniques to enhance these factors in short-term settings are recommended.


Multidrug-resistant Salmonella enterica Serovar Typhimurium Monophasic Variant 4,12:i:- Isolated from Asymptomatic Wildlife in a Catalonian Wildlife Rehabilitation Center, Spain.
Wildlife can act as long-term asymptomatic reservoirs for zoonotic bacteria, such as Salmonella. The prevalence and antimicrobial-susceptibility profiles of Salmonella spp. were assessed in 263 cases in wildlife from 22 animal orders from a wildlife rehabilitation center in Catalonia (NE Spain), September 2013-May 2014. Eleven of 263 tested animals were positive for Salmonella spp., representing an overall prevalence of 4.2%. Prevalences by taxonomic categories were 2% in mammals, 4.7% in birds, and 4.5% in reptiles. By species, one each of European hedgehog (Erinaceus europeus; from a sample of n = 26), Eurasian Eagle Owl (Bubo bubo; n = 2), Barn Owl (Tyto alba; n = 3), Tawny Owl (Strix aluco; n = 20), Egyptian Vulture (Neophron percnopterus; n = 1), Griffon Vulture (Gyps fulvus; n = 1), and Hoopoe (Upupa epops; n = 2), and two each Common Kestrels (Falco tinnunculus; n = 16) and pond sliders (Trachemys scripta; n = 25) were positive for Salmonella. By serotyping, seven of eleven isolates were classified as S. enterica subsp. enterica serovar Typhimurium, and five of seven belonged to the monophasic variant 4,12:i:-. All the monophasic variants were isolated from birds (4/5 in raptors) and showed a multidrug-resistance (MDR) profile to at least ampicillin, streptomycin, sulfonamide, and tetracycline (R-type ASSuT), and up to 12 antibiotics. The large proportion of S. Typhimurium monophasic MDR strains detected in wildlife never treated with antibiotics, especially in raptors, adds more complexity to the epidemiologic control of one of the most frequent serovars involved in human and livestock infection.


The primary care physician: nephrology interface for the identification and treatment of chronic kidney disease.
This article explores ways in which early identification of chronic kidney disease (CKD) and promotion of the concept of CKD as a modifiable risk can be achieved through transcending traditional primary and secondary care boundaries. National and regional strategies aimed at early identification of CKD in the community are reviewed, together with those aimed at implementation of management to reduce the risk both of progression of CKD and of complications.


Object names and object functions serve as cues to categories for infants.
Can object names and functions act as cues to categories for infants? In Study 1, 14- and 18-month-old infants were shown novel category exemplars along with a function, a name, or no cues. Infants were then asked to "find another one," choosing between 2 novel objects (1 from the familiar category and the other not). Infants at both ages were more likely to select the category match in the function than in the no-cue condition. However, only at 18 months did naming the objects enhance categorization. Study 2 shows that names can facilitate categorization for 14-month-olds as well when a hint regarding the core meaning of the objects (the function of a single familiarization object) is provided.


Variability in Collection and Use of Race/Ethnicity and Language Data in 93 Pediatric Hospitals.
To describe how pediatric hospitals across the USA and Canada collect race/ethnicity and language preference (REaL) data and how they stratify quality and safety metrics using such data. Pediatric hospitals from the Solutions for Patient Safety network (125 US, 6 Canadian) were surveyed between January and March 2018 on collection and use of patient/family race/ethnicity data and patient/family language preference data. The study team created the survey using a formal process including pre-testing. Responses were analyzed using descriptive statistics. Ninety-three of 131 (71%) hospitals completed the survey (87/125 [70%] US, 6/6 [100%] Canadian). Patient race/ethnicity was collected by 95%, parent/guardian race/ethnicity was collected by 31%, and 5/6 Canadian hospitals collected neither. Minimum government race/ethnicity categories were used without modification/addition by 68% of US hospitals. Eleven hospitals (13%) offered a multiracial/multiethnic option. Most hospitals reported collecting language preferences of parent/guardian (81%) and/or patient (87%). A majority provided formal training on data collection for race/ethnicity (70%) and language preferences (70%); fewer had a written policy (41%, 51%). Few hospitals stratified hospital quality and safety measures by race/ethnicity (20% readmissions, 20% patient/family experience, 16% other) or language preference (21% readmissions, 21% patient/family experience, 8% other). The variability of REaL data collection practices among pediatric hospitals highlights the importance of examining the validity and reliability of such data, especially when combined from multiple hospitals. Nevertheless, while improvements in data accuracy and standardization are sought, efforts to identify and eliminate disparities should be developed concurrently using existing data.


Life history and social learning: megapode chicks fail to acquire feeding preferences from conspecifics.
Australian brush-turkeys, Alectura lathami, are birds with an unusual life history: The young receive no parental care and first encounter conspecifics at an unpredictable age. Brush-turkey chicks that were 3-4 days old were presented with a robot model that appeared to feed from a distinctively colored dish. In control training trials, chicks saw a robot standing next to a different dish and scanning from side to side. Chicks expressed a strong tendency to feed from dishes of the type indicated by the pecking robot, but this effect proved ephemeral. Brush-turkeys hence appear to show no social learning under conditions that inculcate stable preferences in other galliforms such as chickens, suggesting that life history plays an important role in the evolution of learning.


'We have to discuss it': cancer patients' advance care planning impressions following educational information about cardiopulmonary resuscitation.
Most cancer patients desire information about care options at the end of life, including cardiopulmonary resuscitation (CPR). Communicating such care options can be challenging and is part of advance care planning (ACP). Our prior studies with video educational media produced data on patients' categoric preferences (yes/no/unsure) for CPR; however, the thematic underpinnings of these educated preferences in patients treated for advanced cancer aren't well known. Qualitative thematic content analysis of participants' responses in a randomized trial of an educational video (V) or narrative (N) about CPR in patients with advanced gastrointestinal cancers. Responses were independently coded and categorized for thematic content by two reviewers. Of 54 study participants, 26 total (41% of V arm, 56% of N arm) articulated questions, comments, or both. Reviewer analyses demonstrated thematic consensus and resulted in seven distinct themes listed in decreasing order of prevalence: (a) ACP should be started early; (b) educational information about CPR affirmed participants' existing beliefs/knowledge/values about advanced illness; (c) participants were apprehensive about ACP but wanted to discuss it; (d) gaps in knowledge about ACP emerged; (e) CPR information was helpful/acceptable; (f) physicians should be involved in ACP; and (g) medical questions about critical illness arose. Findings identified that while sometimes difficult to discuss, advance care planning is desired, deemed helpful, and ideally begun early by clinicians, and that video education is an appropriate and affirming initiator of discussions. These themes are incorporated into our ongoing research on cancer patient-specific values and education about care options.


Auto-generated materials database of Curie and Néel temperatures via semi-supervised relationship extraction.
Large auto-generated databases of magnetic materials properties have the potential for great utility in materials science research. This article presents an auto-generated database of 39,822 records containing chemical compounds and their associated Curie and Néel magnetic phase transition temperatures. The database was produced using natural language processing and semi-supervised quaternary relationship extraction, applied to a corpus of 68,078 chemistry and physics articles. Evaluation of the database shows an estimated overall precision of 73%. Therein, records processed with the text-mining toolkit, ChemDataExtractor, were assisted by a modified Snowball algorithm, whose original binary relationship extraction capabilities were extended to quaternary relationship extraction. Consequently, its machine learning component can now train with ≤ 500 seeds, rather than the 4,000 originally used. Data processed with the modified Snowball algorithm affords 82% precision. Database records are available in MongoDB, CSV and JSON formats which can easily be read using Python, R, Java and MatLab. This makes the database easy to query for tackling big-data materials science initiatives and provides a basis for magnetic materials discovery.


Finding a diamond in the (mouse is) rough.
In this issue of Blood, Devlin and colleagues use a new strategy to create a mouse model for the inherited bone marrow failure syndrome, DBA.The result, while recapitulating certain aspects of the disease and representing a positive step forward, also demonstrates that significant hurdles remain in faithfully creating a mammalian model for DBA.