[Lipid metabolism. I. Role of insulin in lipid metabolism].
The triacylglyceroles that comprise the bulk of lipids in the diet are hydrolyzed to free fatty acids, monoacylglyceroles and glycerol in the intestinal tract. During absorption through the intestinal tract mucosa, triacylglyceroles are resynthesized from free fatty acids, and glycerol-3-phosphate is formed in the intestinal mucose. these globules, called chylomicrons, pass through the liver and adipose tissue, they are reduced in size by an enzyme, lipoprotein lipase (LPL). In the postabsorptive period, free fatty acids and glycerol are released from adipocytes by neural and hormonal stimulation. The free fatty acids can be burned by almost all tissues of the body except the brain. They are burned in the mitochondria by a process of b-oxidation to acetyl-CoA, which can then enter the citrate acid cycle for conversion to CO2, adenosine triphosphate, and water. When excessive quantities of glucose are ingested, the glucose can be converted to a storage form, triacylglycerol. Fatty acids are synthesized by a series of reactions in which acetyl-CoA and malonylo-CoA residues sequentially condense until the fatty acid chain is completed. The fatty acids are then combined with glycerol-3-phosphate, generated in the liver, to form the neutral triacylglyceroles. The insulin has effects on both the synthetic (estrification) and breakdown (lipolysis) pathways. The promotion of triacylglycerol storage in fat is one of the most important of the actions of insulin.


Probiotic supplementation in marathonists and its impact on lymphocyte population and function after a marathon: a randomized placebo-controlled double-blind study.
Probiotic supplementation arises as playing an immune-stimulatory role. High-intensity and -volume exercise can inhibit immune cell function, which threatens athletic performance and recovery. We hypothesized that 30 days of probiotic supplementation could stabilize the immune system of athletes preventing immune suppression after a marathon race. Twenty-seven male marathonists were double-blinded randomly into probiotic (Bifidobacterium-animalis-subsp.-Lactis (10 × 109) and Lactobacillus-Acidophilus (10 × 109) + 5 g of maltodextrin) and placebo (5 g of maltodextrin) group. They received 30 sachets and supplemented 1 portion/day during 30 days before the race. Blood were collected 30 days before (rest), 1 day before (pre), 1 h after (post) and 5 days after the race (recovery). Both chronic and acute exercise modulated a different T lymphocyte population (CD3+CD4-CD8- T-cells), increasing pre-race, decreasing post and returning to rest values at the recovery. The total number of CD8 T cell and the memory subsets statistically decreased only in the placebo group post-race. Pro-inflammatory cytokine production by stimulated lymphocytes decreased in the probiotic group after the supplementation period. 30 days of probiotic supplementation maintained CD8 T cell and effector memory cell population and played an immunomodulatory role in stimulated lymphocytes. Both, training and marathon modulated a non-classical lymphocyte population regardless of probiotic supplementation.


Morton Filter-Based Security Mechanism for Healthcare System in Cloud Computing.
Electronic health records contain the patient's sensitive information. If these data are acquired by a malicious user, it will not only cause the pilferage of the patient's personal data but also affect the diagnosis and treatment. One of the most challenging tasks in cloud-based healthcare systems is to provide security and privacy to electronic health records. Various probabilistic data structures and watermarking techniques were used in the cloud-based healthcare systems to secure patient's data. Most of the existing studies focus on cuckoo and bloom filters, without considering their throughputs. In this research, a novel cloud security mechanism is introduced, which supersedes the shortcomings of existing approaches. The proposed solution enhances security with methods such as fragile watermark, least significant bit replacement watermarking, class reliability factor, and Morton filters included in the formation of the security mechanism. A Morton filter is an approximate set membership data structure (ASMDS) that proves many improvements to other data structures, such as cuckoo, bloom, semi-sorting cuckoo, and rank and select quotient filters. The Morton filter improves security; it supports insertions, deletions, and lookups operations and improves their respective throughputs by 0.9× to 15.5×, 1.3× to 1.6×, and 1.3× to 2.5×, when compared to cuckoo filters. We used Hadoop version 0.20.3, and the platform was Red Hat Enterprise Linux 6; we executed five experiments, and the average of the results has been taken. The results of the simulation work show that our proposed security mechanism provides an effective solution for secure data storage in cloud-based healthcare systems, with a load factor of 0.9. Furthermore, to aid cloud security in healthcare systems, we presented the motivation, objectives, related works, major research gaps, and materials and methods; we, thus, presented and implemented a cloud security mechanism, in the form of an algorithm and a set of results and conclusions.


Therapeutic efficacy of Kalpaamruthaa on reactive oxygen/nitrogen species levels and antioxidative system in mammary carcinoma bearing rats.
Reactive oxygen species play an important role in cancer and metastasis. Kalpaamruthaa is a modified Siddha preparation, which has been formulated in our laboratory. The preparation is an amalgamation of Semecarpus anacardium (SA), Emblica officinalis (EO) and honey, which gives an extra protectiveness to mammary carcinoma bearing animals (Sprague-Dawley stains were used for this study). The aim of our research is to determine the therapeutic efficiency of the drug with respect to lipid peroxidation and antioxidant status. The levels of lipid peroxides and antioxidant levels were measured in blood, and vital organs (liver, kidney and breast tissue) of control and experimental animals. In cancer condition, the LPO was increased and antioxidant levels were decreased. On drug (SA and KA) administration, decreased LPO and increased antioxidant levels were seen in control and experimental animals. This may be due to additive property of the drugs (SA, Emblica and honey), which possesses anticancer effect. The present study shows the good therapeutic efficacy of Kalpaamruthaa against mammary carcinoma.


Outpatient Joint Arthroplasty: Practical Guidelines for Success, Effect of COVID--19, and the Roles of Technology and Partnering With Industry.
The COVID-19 pandemic has had a drastic effect on the landscape of outpatient joint arthroplasty. By accelerating the migration to ambulatory surgery centers and hospital outpatient departments, protocols and techniques had to adapt quickly. In addition, the roles of technology and partnering with industry became more appealing in some cases to address specific voids and needs during this transition period. The COVID-19 pandemic abruptly affected the state of outpatient joint arthroplasty in 2020 with long-lasting effects that will continue to shape the practice of outpatient total joint arthroplasty for years to come.


Ethnicity in pressure ulcer risk assessment, with specific relation to the Pakistani ethnic minority in Burton, England.
There has been little work on ethnicity related to pressure ulcers in general and little or nothing specific to South Asians, and the Pakistani ethnic group in particular. To explore the relevance of ethnicity in pressure ulcers. All admissions over a 5-year period to a District General Hospital in Burton, United Kingdom (UK) were considered where data were present on Waterlow Score, ethnicity and pressure sore status. Logistic regression analysis was conducted using ethnicity and other variables to predict ulcer formation. RESULTS; Age is predictive, but ethnicity was not found to be a significant predictor. There is no evidence that members of the Pakistani ethnic minority are at higher risk than the majority White population in Burton, with respect to pressure ulcers.


Disability and treatment patterns of multiple sclerosis patients in United States: a comparison of veterans and nonveterans.
The Veterans Health Administration (VHA) is the largest integrated healthcare system in the world and provides care to approximately 20,000 multiple sclerosis (MS) patients. Here, we report that these MS patients are disproportionately more likely to be older, male, unemployed, and disabled with lower levels of education and financial resources when compared to veterans not receiving care within the VHA or to nonveteran MS patients. When comparing the VHA MS patients to a cohort of nonveteran MS patients matched for age, sex, and disability, we found that veterans receiving care within the VHA were equally likely to have received care from a neurologist and more likely to have received care from rehabilitation specialists and primary care physicians than nonveterans. Similarly, veterans in the VHA were more likely to receive therapy with certain symptomatic medications but were less likely to be treated with disease-modifying agents for MS (DMAMS) than nonveterans. When treated with DMAMS, they are more likely to be treated with Avonex and significantly less likely to receive treatment with Copaxone or Novantrone.


Laparoscopic transperitoneal pyelopyelostomy and ureteroureterostomy of retrocaval ureter: Report of two cases and review of the literature.
We report two cases of retrocaval ureter that were successfully treated by a laparoscopic transperitoneal approach. Presentation of both these cases was with flank pain. Ureteroureterostomy using an intracorporeal suture technique was performed for one, and pyelopyelostomy for the other case. Operative time was 120 min and 110 min, respectively. Pyelopyelostomy was technically easier to perform than ureteroureterostomy that required an extra fourth port insertion to facilitate dissection. With increasing experience with the intracorporeal suturing laparoscopic technique of either pyelopyelostomy or ureteroureterostomy should be the first choice for retrocaval ureter.


Increased expression of Bim contributes to the potentiation of serum deprivation-induced apoptotic cell death in Huntington's disease knock-in striatal cell line.
Given that mutant huntingtin may cause dysregulation of gene expression in striatal neurons leading to the neuronal death, we examined the expression level of Bcl-2 interacting mediator of cell death (Bim) in immortalized wild type STHdh(Q7) and knock-in mutant STHdh(Q111) striatal cell lines to understand the underlying mechanism by which mutant huntingtin causes selective death of striatal neurons. Mutant STHdh(Q111) exhibited significantly increased expression level of Bim compared to STHdh(Q7). Serum deprivation resulted in potentiated apoptotic death in STHdh(Q111) compared to STHdh(Q7). However, the expression level of Bim was not changed with serum deprivation in both cell lines. Activation of pro-survival pathway with IGF-1 significantly attenuated serum deprivation-induced neuronal death in both cell lines and attenuated mutant huntingtin-mediated potentiated apoptotic death in STHdh(Q111). The level of active Akt was significantly elevated in STHdh(Q111) compared to STHdh(Q7) resulting in the phosphorylation of a FKHRL1, a forkhead transcription factor regulating Bim expression in neuronal cells. These data suggest that the presence of mutant huntingtin causes transcriptional dysregulation favoring apoptosis and that Akt pro-survival pathway in STHdh(Q111) is not compromised due to the presence of mutant huntingtin. Therefore, activation of this pathway may contribute to the protection of striatal neurons in Huntington's disease.


Feed Composition Differences Resulting from Organic and Conventional Farming Practices Affect Physiological Parameters in Wistar Rats-Results from a Factorial, Two-Generation Dietary Intervention Trial.
Recent human cohort studies reported positive associations between organic food consumption and a lower incidence of obesity, cancer, and several other diseases. However, there are very few animal and human dietary intervention studies that provide supporting evidence or a mechanistic understanding of these associations. Here we report results from a two-generation, dietary intervention study with male Wistar rats to identify the effects of feeds made from organic and conventional crops on growth, hormonal, and immune system parameters that are known to affect the risk of a number of chronic, non-communicable diseases in animals and humans. A 2 × 2 factorial design was used to separate the effects of contrasting crop protection methods (use or non-use of synthetic chemical pesticides) and fertilizers (mineral nitrogen, phosphorus and potassium (NPK) fertilizers vs. manure use) applied in conventional and organic crop production. Conventional, pesticide-based crop protection resulted in significantly lower fiber, polyphenol, flavonoid, and lutein, but higher lipid, aldicarb, and diquat concentrations in animal feeds. Conventional, mineral NPK-based fertilization resulted in significantly lower polyphenol, but higher cadmium and protein concentrations in feeds. Feed composition differences resulting from the use of pesticides and/or mineral NPK-fertilizer had a significant effect on feed intake, weight gain, plasma hormone, and immunoglobulin concentrations, and lymphocyte proliferation in both generations of rats and in the second generation also on the body weight at weaning. Results suggest that relatively small changes in dietary intakes of (a) protein, lipids, and fiber, (b) toxic and/or endocrine-disrupting pesticides and metals, and (c) polyphenols and other antioxidants (resulting from pesticide and/or mineral NPK-fertilizer use) had complex and often interactive effects on endocrine, immune systems and growth parameters in rats. However, the physiological responses to contrasting feed composition/intake profiles differed substantially between the first and second generations of rats. This may indicate epigenetic programming and/or the generation of "adaptive" phenotypes and should be investigated further.


Acute obstructive pancreatitis after pancreas-sparing total duodenectomy in a patient with pancreas divisum: a case report.
Pancreas-sparing total duodenectomy (PSTD) is an ideal recommended procedure for patients with multiple duodenal adenomas or early duodenal cancer. We herein report a rare but serious complication of PSTD. A 20-year-old woman with duodenal adenocarcinoma underwent PSTD. On postoperative day one, she complained of severe abdominal pains. Her serum amylase and serum pancreatic amylase levels were extremely elevated (Amy, 1296 IU/L; P-Amy, 1273 IU/L). With contrast enhanced CT, acute obstructive pancreatitis with pancreas divisum due to the ligation of the dorsal pancreatic duct was highly suspected. An emergency operation was performed to relieve the pancreatic duct obstruction, and an additional anastomosis between the dorsal pancreatic duct and jejunum was performed. The patient's postoperative course was mostly uneventful, and her discomfort improved immediately. When we perform pancreas-sparing total duodenectomy, some form of pancreatography is necessary to exclude pancreas divisum.


Ischemic stroke as the first manifestation of severe ventricular hypertrabeculation/non-compaction.
A rare congenital myocardial defect, known as left ventricular hypertrabeculation/non-compaction (LVHT), has been occasionally described associated with thrombus formation with a potential systemic embolic risk, but its association with ischemic strokes remains controversial. We report a case of ischemic stroke in a patient with severe LVHT and ventricular dysfunction as a possible etiologic synergistic association. In absence of other embolic sources, a severe LVTH associated with ventricular dysfunction could constitute a potential source of brain embolism, especially in patients with high suspicion of an embolic mechanism of ischemic stroke.


Pre- and postnatal developmental toxicity study design for pharmaceuticals.
Assessment of potential developmental and reproductive toxicity of human pharmaceuticals is currently guided by the ICH S5(R2) document. The studies that assess the hazard of both pre- and postnatal exposure are predominantly conducted in rodents (rat and mouse). Utilizing the collective experience of the authors, acceptable designs for both the range-finding and definitive studies are presented with detailed descriptions for the presentation of data. In addition, the suggested initiation and then total duration of these studies in relation to clinical studies are described. Optional parameters that may be included in the studies, as well as possible combination with other study designs are discussed. The details described herein will assist all laboratories performing these studies, individuals who need to plan for the studies, and regulatory agencies that ultimately review these studies.


Subtypes of batterers in treatment: empirical support for a distinction between type I, type II and type III.
This study explores the existence of different types of batterers in a sample of 266 men who had been court referred for intimate partner violence. The data collected in the assessment that have been used to perform a hierarchical and a two-step cluster analysis fall into three areas: aggression towards the partner, general aggression and presence of psychopathology and personality traits, more specifically, alcohol use, borderline and antisocial personality traits, psychopathy traits, state anger and trait anger, anger expression and control, anger, hostility, and, finally, impulsivity. The results show a typology consisting of 3 types of batterers on the basis of violence level and psychopathology: low (65%), moderate (27.8%) and high (7.1%). This study provides empirical support for the development of batterer typologies. These typologies will help achieve early detection of different types of batterers, allowing us to tailor interventions on the basis of the needs of each of the types.


Indirect antigen-trap ELISAs using polyclonal antisera for detection of group B and D Salmonellas in chickens.
Indirect antigen-trap ELISAs able to detect Salmonella typhimurium and S. enteritidis are described. Their limits of sensitivity were about 10(7) organisms in nutrient broth culture. With the ELISA developed for S. typhimurium, 76 of 77 strains gave optical density (OD) readings of 1.06 to 1.40. Three other serotypes from group B in the Kaufmann-White scheme gave high values: S. saintpaul produced an OD of 1.40, S. schwarzengrund 0.93 and S. derby 0.88. Twenty other serotypes all produced OD values of 0.39 to 0.66. Four Citrobacter strains and an E. coli produced lower values. With the S. enteritidis ELISA, seven strains of this serotype produced OD values of 1.13 to 1.23 and 13 other serotypes gave OD values of 0.14 to 0.87. There was good correlation between the ELISA and bacteriological culture after examining selenite broth cultures of cloacal swabs taken from experimentally infected chickens. A few samples were positive by ELISA and negative by culture and vice versa. Similar results were obtained from cloacal swabs taken from a commercial flock known to be infected with S. typhimurium. Much closer correlation existed between the two methods for identifying artificially contaminated eggs or for spleens taken from experimentally infected birds.


[Diagnosis, treatment and prophylaxis of herpes zoster].
In the case of reduced cellular immunity the previously dormant varicella zoster virus (VZV) causes the characteristic belt-shaped vesicular exanthema of herpes zoster. The initial clinical symptoms of herpes zoster are often non-specific and may lead to initial misdiagnosis. A common complication of herpes zoster is postherpetic neuralgia (PHN) but secondary hematogenic dissemination is only rarely observed. In addition to general factors, such as advanced age and female gender, inflammatory rheumatic diseases and their immunosuppressive treatment are important risk factors for the occurrence of herpes zoster. Antiviral therapy initiated in the first 72 h after the onset of exanthema reduces acute symptoms and the risk of complications. The subunit inactivated vaccine, which has been available since 2018, is highly effective and relatively well-tolerated but randomized controlled trials in patients with drug-induced immunosuppression for inflammatory rheumatic diseases are still pending.


Expression of gelatinase B in trachomatous conjunctivitis.
Gelatinase B is a matrix metalloproteinase involved in extracellular matrix (ECM) breakdown often associated with scarring and other pathological disorders. It was investigated whether gelatinase B is involved in the pathogenesis of ECM degradation associated with trachomatous conjunctivitis. Conjunctival biopsy specimens obtained from six patients with active trachoma, six patients with active vernal keratoconjunctivitis (VKC), and seven control subjects were studied. Immunohistochemical techniques and a specific monoclonal antibody against human gelatinase B were used, and a monoclonal antibody against macrophage CD68 to identify mononuclear cells with gelatinase B immunoreactivity. In addition, quantitative zymography was used to compare the activity of gelatinase B in conjunctival biopsy specimens from seven patients with active trachoma and seven control subjects. Gelatinase B was detected by immunohistochemistry only in polymorphonuclear cells located in the vascular lumens in three normal conjunctival biopsy specimens. In all trachoma specimens and in five VKC specimens, gelatinase B was localised in monocyte/macrophage cells, positive for the CD68 marker, and in polymorphonuclear cells. The majority of the latter cell type was located in intravascular spaces. Compared with VKC specimens, trachoma specimens showed significantly more immunoreactive gelatinase B monocyte/macrophage cells (52.3 (21.9) v 8.2 (6.4); p <0.001) and polymorphonuclear cells (23.2 (14.2) v 6.3 (5.4); p = 0. 013). Activated macrophages with giant cell morphology clearly stained with the gelatinase B specific monoclonal antibody were observed in trachoma specimens. Zymography revealed that gelatinase B levels in trachoma specimens were significantly higher than the levels found in normal conjunctiva (1739.6 (1078.3) v 609.3 (395.9) scanning units; p = 0.0127). The increased activity of gelatinase B and numbers of inflammatory cells containing gelatinase B in trachoma specimens suggest that this enzyme plays a part in the pathogenesis of conjunctival scarring in trachoma.


A Low-Cost Filament Winding Technology for University Laboratories and Startups.
This paper systematically explains the methodology and results of empirical work on the development of a low-cost filament winding technology for manufacturing axisymmetric polymer composite structures with a high length-to-diameter ratio, such as tubes, motor casings, and pressure vessels. The principal objective was to examine the experiences and most optimal practices in the development of computer-controlled equipment and auxiliary tooling for the wet filament-winding process. To preclude expensive commercial software for the automated control of a winding machine, analytical equations were derived for the winding trajectory of a four-axis filament-winding machine. The feasibility of the proposed equations was successfully validated by laying the fiber along the geodesic path marked on the surface of a cylindrical mandrel with hemispherical ends. Moreover, the carbon/epoxy cylindrical casings with hemispherical ends and port openings of the same diameter were wound to determine the thickness distribution in the hemispherical dome. The fiber volume ratio in the wound composite parts was evaluated using an optical technique.


The Efficacy of Denosumab in Patients With Rheumatoid Arthritis: A Systematic Review and Pooled Analysis of Randomized or Matched Data.
The purpose of this study was to evaluate the efficacy of denosumab treatment in patients with rheumatoid arthritis (RA). The Medline, Embase and Cochrane Library databases were searched for relevant clinical studies. Studies that assessed the efficacy of denosumab in patients with RA were identified. The primary endpoints were the percent changes in bone mineral density (BMD), and the changes in modified total Sharp score (mTSS), modified Sharp erosion score and joint space narrowing (JSN) score. Pooled analyses were calculated using random-effect models. After searching the literature and performing further detailed assessments, 10 studies with a total of 1758 patients were included in the quantitative analysis. Pooled analyses showed that denosumab treatment significantly increased the percent changes in lumbar spine BMD [mean difference (MD): 5.12, confidence intervals (CI): 4.15 to 6.09], total hip BMD (MD: 2.72, 95% CI: 1.80 to 3.64) and femoral neck BMD (MD: 2.20, 95% CI: 0.94 to 3.46) compared with controls. Moreover, denosumab treatment significantly decreased the changes in mTSS (MD: -0.63, 95% CI: -0.86 to -0.41) and modified Sharp erosion score (MD: -0.62, 95% CI: -0.88 to -0.35). Subgroup analysis indicated that denosumab was superior to bisphosphonates for the improvement of BMD and the mitigation of joint destruction. Denosumab treatment was associated with increased BMD and alleviated progression of joint destruction in RA patients, even when compared with bisphosphonates.


The method of attachment influences accelerometer-based activity data in dogs.
Accelerometer-based activity monitoring is a promising new tool in veterinary medicine used to objectively assess activity levels in dogs. To date, it is unknown how device orientation, attachment method, and attachment of a leash to the collar holding an accelerometer affect canine activity data. It was our goal to evaluate whether attachment methods of accelerometers affect activity counts. Eight healthy, client-owned dogs were fitted with two identical neck collars to which two identical activity monitors were attached using six different methods of attachment. These methods of attachment evaluated the use of a protective case, positioning of the activity monitor and the tightness of attachment of the accelerometer. Lastly, the effect of leash attachment to the collar was evaluated. For trials where the effect of leash attachment to the collar was not being studied, the leash was attached to a harness. Activity data obtained from separate monitors within a given experiment were compared using Pearson correlation coefficients and across all experiments using the Kruskal-Wallis Test. There was excellent correlation and low variability between activity monitors on separate collars when the leash was attached to a harness, regardless of their relative positions. There was good correlation when activity monitors were placed on the same collar regardless of orientation. There were poor correlations between activity monitors in three experiments: when the leash was fastened to the collar that held an activity monitor, when one activity monitor was housed in the protective casing, and when one activity monitor was loosely zip-tied to the collar rather than threaded on using the provided metal loop. Follow-up, pair-wise comparisons identified the correlation associated with these three methods of attachment to be statistically different from the level of correlation when monitors were placed on separate collars. While accelerometer-based activity monitors are useful tools to objectively assess physical activity in dogs, care must be taken when choosing a method to attach the device. The attachment of the activity monitor to the collar should utilize a second, dedicated collar that is not used for leash attachment and the attachment method should remain consistent throughout a study period.


Preparation and characterization of a C-terminal fragment of pregnancy zone protein corresponding to the receptor-binding peptide from human alpha 2-macroglobulin.
Digestion of the pregnancy zone protein with papain at pH 4.5 yields an 18 kDa C-terminal fragment. This fragment consists of the 145 C-terminal amino-acid residues cleaved at Asn-1288 Ile and is homologous to the C-terminal receptor binding fragment of human alpha 2-macroglobulin obtained by cleavage with papain. The fragment contains an intrachain disulfide bond between 1308Cys and 1423Cys corresponding to that between 1304Cys and 1419Cys in alpha 2-macroglobulin. An oligosaccharide chain, is present in the C-terminal fragment of pregnancy zone protein as in human alpha 2-macroglobulin. The PZP C-terminal fragment was demonstrated to bind to the LRP/alpha 2M-receptor. Both the pregnancy zone protein and alpha 2-macroglobulin fragments bind three mAb's (alpha 1:1, R35, and 7H11D6) generated against alpha 2-macroglobulin. The mAb 7H11D6 was generated against the alpha 2-macroglobulin-proteinase complex (Isaacs, I.J., Steiner, J.P., Roche, P.A., Pizzo, S.V. and Strickland, D.K. (1988) J. Biol. Chem. 263, 6709-6714) and the binding of this to the C-terminal fragments of both pregnancy zone protein and alpha 2-macroglobulin indicates that both proteins use the same receptor recognition site for binding to the LRP/alpha 2M-receptor.


Brachytherapy: common pitfalls.
Gynecologic radiation oncology is a demanding area of oncology requiring expertise in external beam and brachytherapy. Both physicians and physicists are called on to use their full complement of skills to employ state-of-the-art treatments to benefit patients. A wide variety of unusual presentations are frequent in gynecology, and hence, it is necessary to have a number of techniques available to offer the optimal treatments. The heterogeneity of treatments and the rarity of certain gynecological presentations lead to complexity and potential error. We reviewed previous gynecological high dose rate brachytherapy treatment images and plans for patients from the past decade and identified examples of common problems to share with the community. The strategies to prevent or recover from these pitfalls are also presented. With increasing number of applicator choices, it is critical for clinics to follow rigorous commissioning steps to ensure treatment process safety as described. The clinics should consider implementing a thorough on-boarding program and regular hands-on practice as a continuous quality improvement measure. The use of checklists can be invaluable and result in fewer human errors. Gynecological chart rounds that focus on brachytherapy are also encouraged. Lastly, an incident learning system to document small deviations that occur in the process, and a rigorous root cause analysis process could help prevent potential future incidents.


Success for All? A Call to Re-examine How Student Success Is Defined in Higher Education.
A central focus in science education is to foster the success of students who identify as Black, Indigenous, and people of color (BIPOC). However, representation and achievement gaps relative to the majority still exist for minoritized students at all levels of science education and beyond. We suggest that majority groups defining the definitions and measures of success may exert "soft power" over minoritized student success. Using a hegemonic and critical race theory lens, we examined five years of research articles in CBE-Life Sciences Education to explore how success was defined and measured and what frameworks guided the definitions of student success. The majority of articles did not explicitly define success, inherently suggesting "everyone knows" its definition. The articles that did define success often used quantitative, academic outcomes like grade point average and exam scores, despite commonly cited frameworks with other metrics. When students defined success, they focused on different aspects, such as gaining leadership skills and building career networks, suggesting a need to integrate student voice into current success definitions. Using these results, we provide suggestions for research, policy, and practice regarding student success. We urge self-reflection and institutional change in our definitions of success, via consideration of a diversity of student voices.


Extracorporeal circulation for tissue transplantation (in the case of venous flaps).
During free-tissue transplantation, recipient vessels are often crushed as a result of trauma or radiation therapy, making anastomosis of vessels difficult. In some cases, a second operation is unavoidable because of formation of a postoperative thrombus at sites of the anastomosis. To solve such problems, it should be possible to transplant tissue anywhere in the body without vascular anastomosis by extracorporeal circulation. This study mainly concerned venous flaps that were spindle-shaped and 4 x 3 cm in size. One hundred and forty-six male Japanese White rabbits, weighing 2.0 to 2.5 kg, were used. Stabilized hemoglobin, lactated Ringer's solution, whole blood, and plasma were used as perfusate. Each of these perfusates was injected at a rate of 5 ml per hour continuously for 3 days in good recipient sites and for 7 days in poor recipient sites. Five rabbits were used in each group. The flaps were examined histologically and electron microscopically. Moreover, in the plasma group, microangiography was performed to observe blood circulation between the flap and the surrounding tissue. The flaps survived in all cases in which the plasma group had good recipient beds but did not survive in any of the other cases, in which degeneration of the endothelial cells was detected prior to edema. According to the results of this examination, tissue viability of the venous flap could be maintained for at least 3 days by perfusion of plasma. During this time, in the cases of good recipient sites, blood may begin to recirculate between the flap and the surrounding tissue.


Subtly impaired humoral immunity predisposes to frequently recurring genital herpes simplex virus type 2 infection and herpetic neuralgia.
Immunogenetic factors predisposing to recurrent genital herpes remain poorly characterized. In a prospective case-control study, 52 consecutive patients with frequently recurring outbreaks of genital herpes were compared with 80 herpes simplex virus (HSV)-seropositive (types 1 and 2) and 70 HSV-seronegative control subjects. Immunoglobulins (Igs), type-specific anti-HSV-2 IgG and IgG subclass antibodies against glycoprotein G, levels of C3 and C4, and classical pathway hemolytic complement activity were measured, and IgG1 and IgG3 allotyping; C4 immunophenotyping; C4* real-time polymerase chain reaction (PCR) genotyping; and HLA-A*, B*, and DR* typing were performed. The G3m(g),G1m(a/a(x)) haplotype was more frequent in patients than in HSV-seronegative control subjects (P=.047). Compared with all control subjects, low levels of total IgG1 (odds ratio [OR], 4.9 [95% confidence interval {CI}, 2.0-12.5]; P=.001) and IgG3 (OR 3.6 [95% CI 1.7-7.8]; P=.001), but not of anti-HSV-2 antibodies, were associated with recurrences. Levels of complement were lowest in patients. The C4* null type was negatively associated with neuralgia (OR, 0.2 [95% CI, 0.06-0.81]; P=.022). Low levels of antibody-dependent cellular cytotoxicity-mediating IgG1 and IgG3 antibodies, partly dependent of allotype, may predispose to recurrent genital herpes. Antibodies produced by T helper type 1 responses, potentially against an unknown epitope, appear to be relevant in recurrences. In patients, C4* deficiencies are associated with protection from herpetic neuralgias, possibly through reduced inflammation.


Managed care's effect on minority physicians and their patients.
Using data from a cross-sectional mail survey that ultimately included 1,215 physicians, the termination and denial rates of minority physicians' managed care contracts across all specialties were compared with nonminority physicians. The study measured termination and denial rates using several variables, including physicians who were denied managed care contracts more than three times in the previous two years. The authors found that 4.4% of the Hispanic physicians, compared with 3.3% of the Caucasian physicians, 6.4% of the African-American physicians, and 5.8% of the Asian physicians, were denied managed care contracts more than three times during this period. The authors also found patient characteristics of those physicians with the highest rates of contract denials and terminations in the state of Maryland, and concluded differences were observed in the selection of physicians by MCOs, even after considering market competition.


Choice of electrocardiographic leads for recording the earliest QRS onset in noninvasive measurements.
A significant error may be introduced in intervals measured from the onset of the QRS if an electrocardiographic lead that does not record the earliest deflection is used. To ascertain to what extent the commonly used leads can be relied on to show the earliest QRS onset, 100 normal subjects and 219 patients with heart disease were studied by means of simultaneous recording of three leads: a right precordial lead chosen to show an rS configuration, lead II, and another limb lead chosen to show a qR configuration. Lead II most frequently showed a delayed QRS onset--in 34% of normal subjects and 36% of the patients. In the other limb lead the initial QRS deflection was delayed in 24% of the normal subjects and 23% of the patients. The QRS onset in the right precordial lead was never delayed in the normal subjects; however, it was delayed in this lead in 6% of the patients. The delays in each of the leads ranged from 5-20 msec. We conclude that while a right precordial lead is by far the most reliable single lead that can be used for interval measurements, simultaneous recording of a right precordial lead and a limb lead assures that recording of the earliest QRS onset in all cases.


Inter-relations between growth hormone, insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1) and sex hormone-binding globulin in acromegaly.
Acromegaly is characterized by a hypersecretion of GH, which in turn results in an excess of IGF-I, an important mediator of its actions. IGF-I itself is intimately related to insulin both in structure and function. IGF-I circulates associated with specific binding proteins which appear to have important effects on its activity. We have examined the inter-relations between GH, prolactin, insulin, IGF-I and one of the binding proteins, IGFBP-1, in 62 patients with acromegaly of varying activity. Serum IGF-I levels were closely related to the logarithm of mean GH levels (r = 0.76; n = 62; P less than 0.001) but multiple regression analysis suggested that, after accounting for the variation due to GH, insulin accounted for some of the additional variation of IGF-I. IGF-I concentrations were independent of prolactin. Fasting insulin levels were high and unrelated to mean GH levels but correlated with those of IGF-I (r = 0.542; n = 57; P less than 0.001). This correlation coefficient was further improved by also accounting for variations in IGFBP-1 (r = 0.684; n = 57; P less than 0.001). Even in subjects whose acromegaly was well controlled or cured, as indicated by GH levels of less than 1 mU/l or IGF-I levels of less than 2 U/ml, fasting insulin levels remained significantly elevated in some individuals. The reason for this persistent abnormality is not clear. Fasting IGFBP-1 levels were low and unrelated to mean GH but were inversely related to fasting insulin levels (r = -0.593; n = 57; P less than 0.001). We propose that a cascade of events occurs in acromegaly.(ABSTRACT TRUNCATED AT 250 WORDS)


Multi-Level Comparative Framework Based on Gene Pair-Wise Expression Across Three Insulin Target Tissues for Type 2 Diabetes.
Type 2 diabetes (T2D) is known as a disease caused by gene alterations characterized by insulin resistance, thus the insulin-responsive tissues are of great interest for T2D study. It's of great relevance to systematically investigate commonalities and specificities of T2D among those tissues. Here we establish a multi-level comparative framework across three insulin target tissues (white adipose, skeletal muscle, and liver) to provide a better understanding of T2D. Starting from the ranks of gene expression, we constructed the 'disease network' through detecting diverse interactions to provide a well-characterization for disease affected tissues. Then, we applied random walk with restart algorithm to the disease network to prioritize its nodes and edges according to their association with T2D. Finally, we identified a merged core module by combining the clustering coefficient and Jaccard index, which can provide elaborate and visible illumination of the common and specific features for different tissues at network level. Taken together, our network-, gene-, and module-level characterization across different tissues of T2D hold the promise to provide a broader and deeper understanding for T2D mechanism.


On-line multi-residue analysis of fluoroquinolones and amantadine based on an integrated microfluidic chip coupled to triple quadrupole mass spectrometry.
An on-line multi-residue qualitative and quantitative analysis method for fluoroquinolones and amantadine using an integrated microfluidic chip was developed prior to directly coupling to triple quadrupole mass spectrometry (QQQ-MS). Six parallel channels consisting of sample filtration units and micro solid phase extraction (micro-SPE) columns were present in the specifically designed microfluidic device. Firstly, the impurities in the sample solution were trapped by the micropillars in the filtration units. The solution passed through the micro-SPE units packed with hydrophilic-lipophilic balanced (HLB) particles, and then the two classes of drugs were enriched. After washing, the targets were eluted and immediately electrosprayed for MS analysis. This approach allowed effective filtration, enrichment, elution, and MS detection without the introduction of an additional separation step after SPE. Direct electrospray ionization (ESI)-MS in multiple reaction monitoring (MRM) mode could not only ensure the high sensitivity of quantitative analysis, but also achieved accurate qualitative analysis towards targets using the MRM ratios, reducing the possibility of false positives. Good linear relationships were obtained by the internal standard (IS) method with a linear range of 1-200 ng mL-1 (R2 > 0.992). The mean recoveries of the eight target analytes were from 85.2% to 122% with the relative standard deviation (RSD) ranging from 5.6% to 20.3%. All this demonstrated that the developed microfluidic device could be a useful tool for rapid detection in the field of food safety.


Auxofuran, a novel metabolite that stimulates the growth of fly agaric, is produced by the mycorrhiza helper bacterium Streptomyces strain AcH 505.
The mycorrhiza helper bacterium Streptomyces strain AcH 505 improves mycelial growth of ectomycorrhizal fungi and formation of ectomycorrhizas between Amanita muscaria and spruce but suppresses the growth of plant-pathogenic fungi, suggesting that it produces both fungal growth-stimulating and -suppressing compounds. The dominant fungal-growth-promoting substance produced by strain AcH 505, auxofuran, was isolated, and its effect on the levels of gene expression of A. muscaria was investigated. Auxofuran and its synthetic analogue 7-dehydroxy-auxofuran were most effective at a concentration of 15 microM, and application of these compounds led to increased lipid metabolism-related gene expression. Cocultivation of strain AcH 505 and A. muscaria stimulated auxofuran production by the streptomycete. The antifungal substances produced by strain AcH 505 were identified as the antibiotics WS-5995 B and C. WS-5995 B completely blocked mycelial growth at a concentration of 60 microM and caused a cell stress-related gene expression response in A. muscaria. Characterization of these compounds provides the foundation for molecular analysis of the fungus-bacterium interaction in the ectomycorrhizal symbiosis between fly agaric and spruce.


Bladder cancer in various population groups in the greater Durban area of KwaZulu-Natal, South Africa.
To study the incidence of different histological types of bladder cancer in various racial groups living within the same geographical region. The study included 615 new patients with bladder cancer seen at three Provincial hospitals in Durban from January 1980 to January 1990. The patients were classified as Caucasian (white people of European descent). African (indigenous black people), Asian (people originating from the Indian subcontinent) or Coloured (people of mixed race). The bladder tumours were classified according to standard histopathological criteria as transitional cell carcinoma, adenocarcinoma or sarcoma. Mixed tumours consisted of both carcinomatous and sarcomatous or undifferentiated elements. Transitional cell carcinoma constituted 95% of the cancers in Caucasians, compared with only 30% in Africans, whereas squamous cell carcinoma occurred in 53% of the African patients, but in only 2% of the Caucasians. In Asian patients, 75% of the tumours were transitional cell and 18% were squamous cell carcinoma, whereas in Coloureds 82% were transitional cell and 9% squamous cell carcinoma. Undifferentiated carcinoma occurred in 8% of African and only 1% of Caucasian patients, whereas adenocarcinoma, mixed tumours and sarcoma occurred in 9% of African patients and only 2% of Caucasian patients. Ova of Schistosoma haematobium were seen in microscopic sections of the bladder tumour in 85% of the patients with squamous cell carcinoma, in 50% of those with undifferentiated tumours and adenocarcinoma, in 17% of those with mixed tumours or sarcoma, and in only 10% of the patients with transitional cell carcinoma. At presentation, African patients were a mean of > 20 years younger than Caucasians. In African patients with squamous cell carcinoma, 90% had stage T3 or T4 disease at presentation, whereas in Caucasian patients with transitional cell carcinoma 76% had stage T1 or T2 disease at presentation. From the study group, it appears that bladder cancer is about six times more common in Caucasians than in Africans. However, the value for Caucasian patients with bladder cancer probably underestimates the true value by about five times, so that bladder cancer in the greater Durban area may be as much as 30 times more common in Caucasians than in Africans. In African patients, endemic Schistosomiasis appears to be related to a high incidence of not only squamous cell carcinoma, but also undifferentiated tumours and adenocarcinoma of the bladder. The effective management of squamous cell carcinoma of the bladder in African patients will depend on the eradication of Schistosomiasis and the early detection of bladder cancer at a stage when it may still be cured by radical treatment.


Activities of daily living and cardiovascular complications following elective, noncardiac surgery.
Algorithms for preoperative cardiac evaluation prior to noncardiac surgery use indices of the metabolic equivalent of activities of daily living (METs). We evaluated METs as a predictor of cardiac complications following elective, noncardiac surgery. A study was performed in an outpatient university preadmission center METs were estimated prospectively for 5,939 inpatients admitted for elective, noncardiac surgery who underwent a preanesthetic assessment within two months prior to surgery. Cardiac outcomes were retrieved retrospectively from relational databases. Outcomes included death, myocardial infarction, acute congestive failure, arrhythmias, cardiac arrest, acute ischemia, acute renalfailure, stroke, respiratory failure, severe hypertension, peripheral vascular occlusion, and pericardial effusion. Adverse outcomes were correlated with age, gender, surgical procedure, activities, and the American Society of Anesthesiologist's Physical Status (ASA-PS) using receiver operator characteristic curve analysis. 94 of 5,939 (1.6 percent) patients had cardiac complications; 16 died, six from their cardiac complication. 38.3 percent of complications occurred following vascular surgery. Using a multinomial logistic regression analysis, both age and physical status were highly significant predictors (p < 0.001) but METs was not (p = 0. 793). Receiver operator characteristic (ROC) curves were usedfor predictive value of variables. Area of the curves for age versus cardiac complications and death were 0.814 and 0.782; for physical status, 0.744 and 0.803; for METs, 0.664 and 0.524. METs are not a reliable index for the prediction of adverse cardiac events following elective, noncardiac surgery. Age and physical status are more predictive. Adverse cardiac outcomes are most frequent following vascular surgery.


Formal Analysis of the Security Protocol with Timestamp Using SPIN.
The verification of security protocols is an important basis for network security. Now, some security protocols add timestamps to messages to defend against replay attacks by network intruders. Therefore, verifying the security properties of protocols with timestamps is of great significance to ensure network security. However, previous formal analysis method of such protocols often extracted timestamps into random numbers in order to simplify the model before modeling and verification, which probably cause time-dependent security properties that are ignored. To solve this problem, a method for verifying security protocols with timestamps using model checking technique is proposed in this paper. To preserve the time-dependent properties of the protocol, Promela (process meta language) is utilized to define global clock representing the protocol system time, timer representing message transmission time, and the clock function representing the passage of time; in addition, a mechanism for checking timestamps in messages is built using Promela. To mitigate state space explosion in model checking, we propose a vulnerable channel priority method of using Promela to build intruder model. We take the famous WMF protocol as an example by modeling it with Promela and verifying it with model checker SPIN (Simple Promela Interpreter), and we have successfully found two attacks in the protocol. The results of our work can make some security schemes based on WMF protocol used in the Internet of things or other fields get security alerts. The results also show that our method is effective, and it can provide a direction for the analysis of other security protocols with timestamp in many fields.


DNA topoisomerases: structure, function, and mechanism.
DNA topoisomerases solve the topological problems associated with DNA replication, transcription, recombination, and chromatin remodeling by introducing temporary single- or double-strand breaks in the DNA. In addition, these enzymes fine-tune the steady-state level of DNA supercoiling both to facilitate protein interactions with the DNA and to prevent excessive supercoiling that is deleterious. In recent years, the crystal structures of a number of topoisomerase fragments, representing nearly all the known classes of enzymes, have been solved. These structures provide remarkable insights into the mechanisms of these enzymes and complement previous conclusions based on biochemical analyses. Surprisingly, despite little or no sequence homology, both type IA and type IIA topoisomerases from prokaryotes and the type IIA enzymes from eukaryotes share structural folds that appear to reflect functional motifs within critical regions of the enzymes. The type IB enzymes are structurally distinct from all other known topoisomerases but are similar to a class of enzymes referred to as tyrosine recombinases. The structural themes common to all topoisomerases include hinged clamps that open and close to bind DNA, the presence of DNA binding cavities for temporary storage of DNA segments, and the coupling of protein conformational changes to DNA rotation or DNA movement. For the type II topoisomerases, the binding and hydrolysis of ATP further modulate conformational changes in the enzymes to effect changes in DNA topology.


From genetics to biotechnology: Synthetic biology as a flexible course-embedded research experience.
The need for changing how science is taught and the expansion of undergraduate research experiences is essential to foster critical thinking in the Natural Sciences. Most faculty research programs only involve a small number of upper-level undergraduate students each semester. The course-based undergraduate research experience (CURE) model enables more students to take ownership over an independent project and experience authentic research. Further, by creating projects that fit into a curriculum's learning goals and student-oriented outcomes, departments help strengthen critical thinking skills in the classroom. Here, we report on the incorporation of a synthetic biology CURE into a mid-level cellular biology course and two advanced level genetics/molecular biology courses. Synthetic biology involves systematic engineering of novel organisms, such as bacteria and plants, to work as functional devices to solve problems in medicine, agriculture, and manufacturing. The value of synthetic biology and its ultimate utility as a teaching tool relies on reusable, standard genetic parts that can be interchanged using common genetic engineering principles. This Synthetic biology CURE effectively achieves five essential goals: (1) a sense of project ownership; (2) self-efficacy: mastery of a manageable number of techniques; (3) increased tolerance for obstacles through challenging research; (4) increased communication skills; and (5) a sense of belonging in a larger scientific community. Based upon our student assessment data, we demonstrate that this course-based synthetic biology laboratory engages students directly in an authentic research experience and models important elements of collaboration, discovery, iteration, and critical thinking.


Searching for prevention.
The pitfalls of prevention are how we commonly think of high-risk groups, multideterminate causation, social change, community psychiatry and mental health. All of these pitfalls stem from a common trap in our thinking about living in terms of a cleavage between normality and abnormality. An alternative view of effective living is presented called The Vital Process. Vitality is seen as the key to prevention. Vitality emerges out of the challenge of facing our inner desperation. Living is making vitality out of desperation. We turn craziness into creativity, rage into courage, panic into initiative, violence into dynamism, hopelessness into achievement and self waste into self fulfillment. When we refuse to face our inner desperation we are at risk for its overwhelming us. Psychiatric diagnoses make this worse. They describe static pictures assumed to be abnormalities foreign to normal people. They make us more fearful and more blocked. The key to effecting prevention is making this idea of vitality central to our work roles. Doing this should replace the bureaucratic in our social institutions with a vital energy. The place for a vital psychiatry should be working directly in such social institutions and sharing responsibility for them. The path for changing these institutions is through leadership imbued with vitality. This in the end resolves into an issue of political leadership. The gain to be derived from such a rethinking of society is a greatly more effective mobilization of our human creativity resources. This is identical with preventing the psychiatric.


Identification of essential filovirion-associated host factors by serial proteomic analysis and RNAi screen.
An assessment of the total protein composition of filovirus (ebolavirus and marburgvirus) virions is currently lacking. In this study, liquid chromatography-linked tandem mass spectrometry of purified ebola and marburg virions was performed to identify associated cellular proteins. Host proteins involved in cell adhesion, cytoskeleton, cell signaling, intracellular trafficking, membrane organization, and chaperones were identified. Significant overlap exists between this data set and proteomic studies of disparate viruses, including HIV-1 and influenza A, generated in multiple cell types. However, the great majority of proteins identified here have not been previously described to be incorporated within filovirus particles. Host proteins identified by liquid chromatography-linked tandem mass spectrometry could lack biological relevance because they represent protein contaminants in the virus preparation, or because they are incorporated within virions by chance. These issues were addressed using siRNA library-mediated gene knockdown (targeting each identified virion-associated host protein), followed by filovirus infection. Knockdown of several host proteins (e.g. HSPA5 and RPL18) significantly interfered with ebolavirus and marburgvirus infection, suggesting specific and relevant virion incorporation. Notably, select siRNAs inhibited ebolavirus, but enhanced marburgvirus infection, suggesting important differences between the two viruses. The proteomic analysis presented here contributes to a greater understanding of filovirus biology and potentially identifies host factors that can be targeted for antiviral drug development.


Clinically significant carbamazepine drug interactions: an overview.
Knowledge of the principles of drug action and distribution contributes to an understanding of the occurrence of drug interactions. The pharmacologic action of most drugs is postulated to occur by the formation of a drug-receptor complex at the site of action that is capable of altering the physiologic response of the target system. The therapeutic response observed depends on the sum of the numerous factors that can affect the disposition pattern of a drug. In an individual, the response to a given drug dose remains relatively constant, but in a large population, a fixed dose can produce a range of plasma concentrations and therefore varied clinical responses. For most drugs, there is a linear relationship between the total dose and the plasma concentration achieved at steady state. Saturation, or zero-order, kinetics accounts for nonlinear increases in drug concentration with dosage increase. Drug-drug interactions with carbamazepine include several types. (1) Autoinduction of carbamazepine metabolism increases the carbamazepine clearance rate, decreases the half-life, and decreases serum concentrations; the clinician must reevaluate a patient's serum levels at 4 to 6 weeks after initiation of therapy. (2) Carbamazepine induces the metabolism of other antiepileptic drugs, enhancing the clearance of phenytoin, primidone, valproic acid, clonazepam, and ethosuximide. (3) Other drugs added to the epileptic patient's drug regimen may induce the metabolism of carbamazepine, causing increased serum concentrations. (4) Inhibition of carbamazepine metabolism by other drugs can also occur; symptoms of drug intoxication rapidly follow. Interactions occur between carbamazepine and macrolide antibiotics, cimetidine, propoxyphene, and isoniazid. Drug-drug interactions are preventable.(ABSTRACT TRUNCATED AT 250 WORDS)


Virtual Reality in the Neurosciences: Current Practice and Future Directions.
Virtual reality has made numerous advancements in recent years and is used with increasing frequency for education, diversion, and distraction. Beginning several years ago as a device that produced an image with only a few pixels, virtual reality is now able to generate detailed, three-dimensional, and interactive images. Furthermore, these images can be used to provide quantitative data when acting as a simulator or a rehabilitation device. In this article, we aim to draw attention to these areas, as well as highlight the current settings in which virtual reality (VR) is being actively studied and implemented within the field of neurosurgery and the neurosciences. Additionally, we discuss the current limitations of the applications of virtual reality within various settings. This article includes areas in which virtual reality has been used in applications both inside and outside of the operating room, such as pain control, patient education and counseling, and rehabilitation. Virtual reality's utility in neurosurgery and the neurosciences is widely growing, and its use is quickly becoming an integral part of patient care, surgical training, operative planning, navigation, and rehabilitation.


Autoantibody-associated cross-reactive idiotype-bearing human B lymphocytes: distribution and characterization, including Ig VH gene and CD5 antigen expression.
Monoclonal antibodies (MoAbs) specific for autoantibody associated cross-reactive idiotypes (CRIs) frequently recognize the Igs of neoplastic B cells in patients with chronic lymphocytic leukemia (CLL) and/or Waldenstrom's macroglobulinemia. Very little is known regarding the normal B cells expressing CRIs (CRI-positive B cells). Using a variety of MoAbs against CRIs we investigated the distribution and topographic localization of CRI-positive B cells in normal adult human lymphoid tissues. We found that CRI-positive B cells represent a significant B-cell subpopulation expressing surface IgM (greater than 90%), IgG (approximately 5%), or IgA (approximately 2%). CRI-positive B cells are homogeneously distributed throughout all lymphoid tissues, accounting for 10% to 15% of all B lymphocytes, with the exception of the thymus, in which they represent the predominant B cell population. Immunophenotypic studies showed (1) that a small subpopulation (3.7% +/- 0.8%) of CRI-positive B cells are activated in vivo, based on CD25 and CD38 antigen expression; and (2) that approximately 50% of CRI-positive B cells express the 67-Kd pan-T-lymphocyte CD5 antigen, suggesting that the CRI-positive B-cell subset and the recently described CD5-positive B-cell subset are closely related. This hypothesis is supported by the fact that CRI-positive B cells produce oligo or polyreactive Igs, which are a characteristic feature of CD5-positive B cells, and also by the fact that both B-cell subpopulations appear to use similar and restricted Ig VH gene family members.


Role of smooth muscle cells in Cardiovascular Disease.
Normally, smooth muscle cells (SMCs) are localized in the tunica media of the vasculature, where they take responsibility for vascular contraction and extracellular matrix (ECM) generation. SMCs also play a significant role in obedience and elastic rebound of the artery in response to the haemodynamic condition. However, under pathological or stressed conditions, phenotype switching from contractile to synthetic state or other cell types will occur in SMCs to positively or negatively contribute to disease progression. Various studies demonstrated that functional changes of SMCs are implicated in several cardiovascular diseases. In this review, we present the function of vascular SMCs (VSMCs) and the involved molecular mechanisms about phenotype switching, and summarize the roles of SMCs in atherosclerosis, hypertension, arterial aneurysms and myocardial infarction, hoping to obtain potential therapeutic targets against cardiovascular disease in the clinical practices.


Aberration-corrected aspheric grating designs for the Lyman/Far-Ultraviolet Spectroscopic Explorer high-resolution spectrograph: a comparison.
Two approaches to reducing the optical aberrations of concave diffraction gratings have been studied to obtain candidate grating designs for the Lyman/Far-Ultraviolet Spectroscopic Explorer mission. The first approach involves shaping the grating substrate while using straight and equally spaced grooves. The second approach involves using a gating substrate with a relatively simple figure and holographically controlling the groove curvature and spacing. We analyze and compare specific designs derived from both approaches.


Blade atrial septostomy: experience with the first 50 procedures.
We have performed 50 blade and balloon atrial septostomies in 46 patients with diagnoses of transposition of the great arteries--32 patients; mitral atresia or stenosis--10 patients; total anomalous pulmonary venous drainage--2 patients; tricuspid atresia--1 patient; and pulmonary valve atresia with hypoplastic right ventricle--1 patient. The patients' age ranged from 1 day to 72 months (median = 8 months) and weights ranged from 2.7 to 14.5 kg. In patients with transposition the systemic saturation increased from an average of 62% to 74.6% (p less than 0.001) and the inter-atrial mean pressure gradient was reduced from 7.74 +/- 5.3 to 1.4 +/- 2.04 mm Hg. Patients with mitral atresia had no significant increase in systemic arterial saturation but a significant decrease in the mean inter-atrial gradient from 19.6 +/- 12.4 to 3.8 +/- 5.3 mm Hg. In three patients the blade septostomy was unsuccessful for technical reasons and the condition of the patient. Complications included one death due to atrial laceration, blood loss requiring transfusion in 5 patients, transient CVA in one patient, and failure of the blade to close in one patient. We have found the palliative use of the blade catheter in conjunction with balloon atrial septostomy to be an effective and safe procedure.


Insertional mutagenesis: neoplasia arising from retroviral integration.
The integration of retroviral proviruses near cellular genes can profoundly affect their expression. Painstaking analysis of insertion sites from a large number of tumors has revealed a number of previously unknown proto-oncogenes, and has elucidated new mechanisms whereby known proto-oncogenes can be activated. A number of these genes have been implicated in tumors of clinical relevance. At the time of writing a great deal remains to be learned of the normal function of these genes in the cell. While it has yet to be demonstrated that retroviral insertion mechanisms play some role in naturally occurring human neoplasms, they must be considered in the context of retroviral gene therapy protocols now being contemplated.


Spatial and temporal expression pattern of Bombyx fork head/SGF-1 gene in embryogenesis.
The embryonic expression of Bombyx fkh/SGF-1 gene has been analysed using in situ hybridization and immunohistochemistry. Both transcripts and protein were first detected in the most anterior and posterior regions at the time of germ anlage formation, and were successively expressed in the foregut and hindgut at later stages. A weaker expression was also detected in the elongated midgut. By the time embryo retraction was finished transcripts and protein were also detectable in the invaginated whole silk glands, and after the blastokinesis stage the products were restricted to the middle and posterior silk glands achieving a state required for the SGF-1 distribution for later stages. Expression could also be detected in the central and peripheral nervous systems. From these observations, we propose that Bombyx Fkh/SGF-1 may play a role in organogenesis processes such as those of the gut, silk glands, and nervous systems, act as a region specific homeotic gene, and in spite of clear embryonic developmental differences between Drosophila and Bombyx, two terminals may be determined by region specific genes such as Bombyx fkh/SGF-1 as opposed to segmental development.


Identification of anaplastic lymphoma kinase fusion in clear cell renal carcinoma (ALK-tRCC): a precision oncology medicine case report.
Translocation-associated renal cell carcinoma involving ALK (ALK-tRCC) is a rare subtype of adult renal cell carcinoma (RCC) reported in recent years. A new Italian case of ALK-tRCC was reported. The patient was a female 44-year-old with a metastatic and pretreated RCC. The tumor showed a rearrangement of ALK gene in tumor cells detected by targeted next-generation sequencing panel. The patient received oral alectinib therapy and achieved a partial response. ALK-tRCC is a rare subtype of adult RCC. Its diagnosis is very difficult because the genomic alteration spectrum is very wide. We suggested that metastatic RCCs should be screened for uncommon genomic alterations expecially in good performance status pretreated resistant/refractory patients.


Nucleic acid duplexes incorporating a dissociable covalent base pair.
We have used molecular modeling techniques to design a dissociable covalently bonded base pair that can replace a Watson-Crick base pair in a nucleic acid with minimal distortion of the structure of the double helix. We introduced this base pair into a potential precursor of a nucleic acid double helix by chemical synthesis and have demonstrated efficient nonenzymatic template-directed ligation of the free hydroxyl groups of the base pair with appropriate short oligonucleotides. The nonenzymatic ligation reactions, which are characteristic of base paired nucleic acid structures, are abolished when the covalent base pair is reduced and becomes noncoplanar. This suggests that the covalent base pair linking the two strands in the duplex is compatible with a minimally distorted nucleic acid double-helical structure.


Risk and asset-based strategies in health: priorities in biomedical, life and environmental science literature since the early twentieth century. A rapid review.
In biomedical, life or environmental science research, two different strategies exist depending on the starting point of the researchers: "what makes us ill? " or "what makes us healthy?". Indeed, a risk-based strategy (RBS) attempts to minimize risk factors increasing the likelihood of developing a disease, while an asset-based strategy (ABS) attempts to promote and strengthen the factors that support good health and wellbeing. We provided an up-to-date overview of both research strategies in peer-reviewed scientific literature, in the fields of human health, animal and plant health and ecosystem health, to fit with the One Health framework. More particularly, we focused on human health by studying publications related to the COVID-19 at the beginning of the pandemic. A rapid review of research science literature was carried out to identify in the PubMed/MEDLINE database the proportion of peer-reviewed articles adopting either a RBS or an ABS, in the main global environment fields from January 01, 1900 to December 31, 2019 and, related to COVID-19, from December 1, 2019 to May 31, 2020. The number of published articles resulting from our search was 1,957,905, including 91.3% with an RBS and 8.7% with an ABS. When examining each field, we found that only 10.5% of human health articles deal with ABS, 5.5% for animal health, 2.2% for ecosystem health, 1.0% for plant health and 2.7% for environmental media. We noted that articles adopting both strategies were published in all health fields. Among the articles concerning COVID-19, 5,854 (55.9%), 542 articles (5.2%) adopted RBS and ABS, respectively, while 4069 (38.9%) simultaneously presenting both strategies. Our results have allowed us to take stock of the biomedical research strategies prioritized during the twentieth century. It seems highly likely that the two strategies we have analyzed can now be chosen in such a way as to promote a balance in public health measures, at every level to guide One Health interventions aimed at helping people, animals, and plants to lead healthier lives.


Plastome structure and adaptive evolution of Calanthe s.l. species.
Calanthe s.l. is the most diverse group in the tribe Collabieae (Orchidaceae), which are pantropical in distribution. Illumina sequencing followed by de novo assembly was used in this study, and the plastid genetic information of Calanthe s.l. was used to investigate the adaptive evolution of this taxon. Herein, the complete plastome of five Calanthe s.l. species (Calanthe davidii, Styloglossum lyroglossa, Preptanthe rubens, Cephalantheropsis obcordata, and Phaius tankervilliae) were determined, and the two other published plastome sequences of Calanthe s.l. were added for comparative analyses to examine the evolutionary pattern of the plastome in the alliance. The seven plastomes ranged from 150,181 bp (C. delavayi) to 159,014 bp (C. davidii) in length and were all mapped as circular structures. Except for the three ndh genes (ndhC, ndhF, and ndhK) lost in C. delavayi, the remaining six species contain identical gene orders and numbers (115 gene). Nucleotide diversity was detected across the plastomes, and we screened 14 mutational hotspot regions, including 12 non-coding regions and two gene regions. For the adaptive evolution investigation, three species showed positive selected genes compared with others, C. obcordata (cemA), S. lyroglossa (infA, ycf1 and ycf2) and C. delavayi (nad6 and ndhB). Six genes were under site-specific positive selection in Calanthe s.l., namely, accD, ndhB, ndhD, rpoC2, ycf1, and ycf2, most of which are involved in photosynthesis. These results, including the new plastomes, provide resources for the comparative plastome, breeding, and plastid genetic engineering of orchids and flowering plants.


IgG4-related Diaphragmatic Inflammatory Pseudotumor.
A 71-year-old man underwent surgery for a pancreatic neuroendocrine tumor. Follow-up imaging showed swelling of the remnant pancreas, and he was histologically diagnosed with autoimmune pancreatitis based on endoscopic ultrasonography-guided fine-needle aspiration specimens. After two years, a tumor appeared on the liver surface. Although we planned to perform laparoscopic partial hepatectomy, the intraoperative findings showed that the tumor was located in the diaphragm. Partial resection of the diaphragm was performed, and the final diagnosis was an immunoglobulin G4-related inflammatory pseudotumor in the diaphragm. To our knowledge, this is the first reported case of an immunoglobulin G4-related diaphragmatic inflammatory pseudotumor.


Mechanism of synergy between TATA and initiator: synergistic binding of TFIID following a putative TFIIA-induced isomerization.
The TFIID complex interacts with at least three types of core promoter elements within protein-coding genes, including TATA, initiator (Inr), and downstream promoter elements. We have begun to explore the mechanism by which the TFIID-Inr interaction leads to functional synergy between TATA and Inr elements during both basal and activated transcription. In DNase I footprinting assays, GAL4-VP16 recruited TFIID-TFIIA to core promoters containing either a TATA box, an Inr, or both TATA and Inr elements, with synergistic interactions apparent on the TATA-Inr promoter. Appropriate spacing between the two elements was essential for the synergistic binding. Despite the sequence-specific TFIID-Inr interactions, gel shift experiments revealed that TFIID alone possesses similar affinities for the TATA-Inr and TATA promoters. Interestingly, however, recombinant TFIIA strongly and selectively enhanced TFIID binding to the TATA-Inr promoter, with little effect on binding to the TATA promoter. Studies of the natural adenovirus major late promoter confirmed these findings, despite the existence of specific but nonfunctional TFIID interactions downstream of the Inr in that promoter. These results suggest that a TFIIA-induced conformational change is essential for the sequence-specific TFIID-Inr interaction to occur with sufficient affinity to support the functional synergism between TATA and Inr elements.


Development and Assessment of Machine Learning Models for Individualized Risk Assessment of Mastectomy Skin Flap Necrosis.
To develop, validate, and evaluate ML algorithms for predicting MSFN. MSFN is a devastating complication that causes significant distress to patients and physicians by prolonging recovery time, compromising surgical outcomes, and delaying adjuvant therapy. We conducted comprehensive review of all consecutive patients who underwent mastectomy and immediate implant-based reconstruction from January 2018 to December 2019. Nine supervised ML algorithms were developed to predict MSFN. Patient data were partitioned into training (80%) and testing (20%) sets. We identified 694 mastectomies with immediate implant-based reconstruction in 481 patients. The patients had a mean age of 50 ± 11.5 years, years, a mean body mass index of 26.7 ± 4.8 kg/m 2 , and a median follow-up time of 16.1 (range, 11.9-23.2) months. MSFN developed in 6% (n = 40) of patients. The random forest model demonstrated the best discriminatory performance (area under curve, 0.70), achieved a mean accuracy of 89% (95% confidence interval, 83-94), and identified 10 predictors of MSFN. Decision curve analysis demonstrated that ML models have a superior net benefit regardless of the probability threshold. Higher body mass index, older age, hypertension, subpectoral device placement, nipple-sparing mastectomy, axillary nodal dissection, and no acellular dermal matrix use were all independently associated with a higher risk of MSFN. ML algorithms trained on readily available perioperative clinical data can accurately predict the occurrence of MSFN and aid in individualized patient counseling, preoperative optimization, and surgical planning to reduce the risk of this devastating complication.


Association of HLA-DR4 (DRB1*0404) with human papillomavirus infection in patients with focal epithelial hyperplasia.
To determine gene frequencies of HLA-DR alleles in 22 Mexican patients with focal epithelial hyperplasia and compare them with those present in ethnically matched healthy subjects, as well as to determine the types of human papillomavirus present in the lesions. Prospective and retrospective observational study. Dermatology outpatient clinic in a general hospital. Twenty-two patients with clinically and histologically confirmed focal epithelial hyperplasia seen within a 10-year period. None. Results of high-resolution DNA typing for HLA-DR alleles and biopsy for viral typing. HLA-DR4 (DRB1*0404) was significantly increased (P<.001; odds ratio, 3.9; 95% confidence interval, 1.86-8.03). Seventeen (85%) of 20 patients had human papillomavirus subtype 13. The data on human papillomavirus differed from reports elsewhere that described association with human papillomavirus type 32. The HLA-DRB1*0404 allele suggests that Amerindian populations are at risk, and in this group, the Mexican population studied was affected only by human papillomavirus type 13.


Influence of stereotyping in smoking cessation counseling by primary care residents.
This study examined racial differences in primary care residents' rates of addressing smoking cessation. We expected residents to have higher rates of addressing cessation with White female patients as compared with African-American or Hispanic female patients, due, in part, to residents having higher outcome expectancies, self-efficacy, lower barriers, and less reliance on stereotypes. Residents (N = 90) were an average of 31 years old; two-thirds were White internal medicine residents. Residents viewed a video of a lower-middle class White, African-American, or Hispanic female interacting with her physician about stomach pain. Results indicate that residents were very likely to address smoking cessation, regardless of patients' race. Compared to residents assigned to an ethnic minority patient, residents assigned to the White patient were less likely to believe the patient would follow their advice (P < .03) and also perceived more barriers to address smoking cessation (P < .04). Reliance on the stereotype of Whites mediated the racial difference in outcome expectancies. Implications are that residents may be relying on stereotypes when they assess lower-middle class White female patients' receptivity to smoking cessation advice. Future research on the role of stereotyping in medical settings is warranted.


Genetic and physiological analysis of germination efficiency in maize in relation to nitrogen metabolism reveals the importance of cytosolic glutamine synthetase.
We have developed an approach combining physiology and quantitative genetics to enhance our understanding of nitrogen (N) metabolism during kernel germination. The physiological study highlighted the central role of glutamine (Gln) synthetase (GS) and Gln synthesis during this developmental process because a concomitant increase of both the enzyme activity and the amino acid content was observed. This result suggests that Gln is acting either as a sink for ammonium released during both storage protein degradation and amino acid deamination or as a source for amino acid de novo synthesis by transamination. In the two parental lines used for the quantitative genetics approach, we found that the increase in Gln occurred earlier in Io compared with F(2), a result consistent with its faster germinating capacity. The genetic study was carried out on 140 F6 recombinant inbred lines derived from the cross between F(2) and Io. Quantitative trait locus mapping identified three quantitative trait loci (QTLs) related to germination trait (T50, time at which 50% of the kernels germinated) that explain 18.2% of the phenotypic variance; three QTLs related to a trait linked to germination performance, kernel size/weight (thousand kernels weight), that explain 17% of the phenotypic variance; two QTLs related to GS activity at early stages of germination that explain 17.7% of the phenotypic variance; and one QTL related to GS activity at late stages of germination that explains 7.3% of the phenotypic variance. Coincidences of QTL for germination efficiency and its components with genes encoding cytosolic GS (GS1) and the corresponding enzyme activity were detected, confirming the important role of the enzyme during the germination process. A triple colocalization on chromosome 4 between gln3 (a structural gene encoding GS1) and a QTL for GS activity and T50 was found; whereas on chromosome 5, a QTL for GS activity and thousand kernels weight colocalized with gln4, another structural gene encoding GS1. This observation suggests that for each gene, the corresponding enzyme activity is of major importance for germination efficiency either through the size of the grain or through its faster germinating capacity. Consistent with the possible nonoverlapping function of the two GS1 genes, we found that in the parental line Io, the expression of Gln3 was transiently enhanced during the first hours of germination, whereas that of gln4 was constitutive.


Increased mitochondrial DNA and RNA polymerase activity in ethylene-treated potato tubers.
A purified mitochondrial fraction was isolated from potato (Solanum tuberosum L.) tubers respiring normally at 23 degrees C or at an accelerated rate in response to treatment with ethylene (10 microliters per liter).A pronounced increase in various mitochondrial enzymic activities was observed in response to exposure of the whole tubers to ethylene. Cytochrome c oxidase activity increased more than 50%, DNA polymerase activity increased about 2-fold, and RNA polymerase activity increased 2.5-fold. Moreover, DNA or RNA polymerase activities of mitochondria isolated from tubers not treated with ethylene were not affected by ethylene treatment in vitro. Respiratory control ratios decreased from 2.84 to 1.50 with increasing periods of ethylene treatment from 0 to 15 hours. None of these changes were observed in untreated tubers. It is concluded that the stimulation of respiration by ethylene in potato tubers is accompanied in vivo by an enhancement of mitochondrial enzymic activity of both membrane-associated enzymes which participate in the mitochondrial oxidative electron transport as well as soluble enzymes which are not directly involved in respiration.


How Ancestral Trauma Informs Patients' Health Decision Making.
This article considers intergenerational trauma by drawing on the experience of a 37-year-old Black woman whose great-grandfather died as a result of involuntary involvement in the US Public Health Service Syphilis Study at Tuskegee. Although she never met her great-grandfather, the abuse, exploitation, and human rights violations he suffered at the hands of the US government profoundly influenced her health experiences. This article contextualizes her experiences in light of past medical abuse and microethics.


The reorganization of mine labor recruitment in Southern Africa: evidence from Botswana.
"The past decade has been one of unprecedented change in the pattern and organization of mine labor recruitment in Southern Africa. Using detailed data on recruitment patterns in Botswana, this article supports the view that recent changes have initiated a self-sustaining trend whereby certain flows of foreign labor into South Africa will decline unabated into the foreseeable future. This results from a shift in general recruiting policy from one of encouraging external migrant labor flows--by expanding recruitment networks and employing a variable and transient workforce--to one of retrenchment and labor stabilization biased in favor of internalized labor supplies."


The pathophysiology of venous thromboembolism: implications with compression garments.
The highest risk of venous thromboembolism lies with abdominoplasty and liposuction and deaths increase when combined with other procedures. The objective of this study was to evaluate physiologic changes in the deep venous system with compression-garments and asses whether there is a correlation between these procedures, rectus plication, and garments. Part 1 of this article is a retrospective review of all office surgical incidents that resulted in an abdominoplasty and/or liposuction death in the state of Florida over the past 8 years. Part 2 is a clinical study, evaluating the effect compression garments have on the pathophysiology of venous thromboembolism. Duplex ultrasounds were performed with and without garments to evaluate venous changes. Literature was reviewed related to intraabdominal pressure and high-tension abdominal closures and surgeons were polled about their use of rectus plication and garments/binders. In 8 years, 13 patients died related to abdominoplasty, liposuction, or the combination of the 2. In 100% of subjects, ultrasounds showed a decrease in venous flow, proximal vessel dilation, and loss of normal biphasic flow within the popliteal vein. Multiple publications have reported an increased morbidity and mortality related to liposuction and abdominoplasty procedures. The most frequent cause of death with these types of procedures was thromboembolism, and we discuss possible reasons for this increased rate. The exact cause of deep venous thrombosis in these procedures remains unknown, but postoperative garments may affect the physiology of venous flow, and may be involved in the formation of deep venous thrombosis and should be considered along with other patient safety procedures.


Computational aspects in mechanical modeling of the articular cartilage tissue.
This review focuses on the modeling of articular cartilage (at the tissue level), chondrocyte mechanobiology (at the cell level) and a combination of both in a multiscale computation scheme. The primary objective is to evaluate the advantages and disadvantages of conventional models implemented to study the mechanics of the articular cartilage tissue and chondrocytes. From monophasic material models as the simplest form to more complicated multiscale theories, these approaches have been frequently used to model articular cartilage and have contributed significantly to modeling joint mechanics, addressing and resolving numerous issues regarding cartilage mechanics and function. It should be noted that attentiveness is important when using different modeling approaches, as the choice of the model limits the applications available. In this review, we discuss the conventional models applicable to some of the mechanical aspects of articular cartilage such as lubrication, swelling pressure and chondrocyte mechanics and address some of the issues associated with the current modeling approaches. We then suggest future pathways for a more realistic modeling strategy as applied for the simulation of the mechanics of the cartilage tissue using multiscale and parallelized finite element method.


The eminent need for an academic program in universities to teach nanomedicine.
Nanomedicine is on the cutting edge of technology applied to medical and biological sciences. Nanodevices, nanomaterials, nanoinstruments, nanotechnologies, and nanotechniques (laboratory methods and procedures) are important for the modern practice of medicine and essential for research that could stimulate the discovery of new medical advances. Accordingly, there is an eminent need for implementing an academic program in universities to teach this indispensable and pragmatic discipline, especially in the departments of graduate studies and research in the areas of pharmacology, genetic engineering, proteomics, and molecular and cellular biology.


An Arabidopsis introgression zone studied at high spatio-temporal resolution: interglacial and multiple genetic contact exemplified using whole nuclear and plastid genomes.
Gene flow between species, across ploidal levels, and even between evolutionary lineages is a common phenomenon in the genus Arabidopsis. However, apart from two genetically fully stabilized allotetraploid species that have been investigated in detail, the extent and temporal dynamics of hybridization are not well understood. An introgression zone, with tetraploid A. arenosa introgressing into A. lyrata subsp. petraea in the Eastern Austrian Forealps and subsequent expansion towards pannonical lowlands, was described previously based on morphological observations as well as molecular data using microsatellite and plastid DNA markers. Here we investigate the spatio-temporal context of this suture zone, making use of the potential of next-generation sequencing and whole-genome data. By utilizing a combination of nuclear and plastid genomic data, the extent, direction and temporal dynamics of gene flow are elucidated in detail and Late Pleistocene evolutionary processes are resolved. Analysis of nuclear genomic data significantly recognizes the clinal structure of the introgression zone, but also reveals that hybridization and introgression is more common and substantial than previously thought. Also tetraploid A. lyrata and A. arenosa subsp. borbasii from outside the previously defined suture zone show genomic signals of past introgression. A. lyrata is shown to serve usually as the maternal parent in these hybridizations, but one exception is identified from plastome-based phylogenetic reconstruction. Using plastid phylogenomics with secondary time calibration, the origin of A. lyrata and A. arenosa lineages is pre-dating the last three glaciation complexes (approx. 550,000 years ago). Hybridization and introgression followed during the last two glacial-interglacial periods (since approx. 300,000 years ago) with later secondary contact at the northern and southern border of the introgression zone during the Holocene. Footprints of adaptive introgression in the Northeastern Forealps are older than expected and predate the Last Glaciation Maximum. This correlates well with high genetic diversity found within areas that served as refuge area multiple times. Our data also provide some first hints that early introgressed and presumably preadapted populations account for successful and rapid postglacial re-colonization and range expansion.


Multi-Morbidity in the Older Person: An Examination of Polypharmacy and Socioeconomic Status.
There has been increased focus on clinically managing multi-morbidity in the older population, but it can be challenging to find appropriate paradigm that addresses the socio-economic burden and risk for polypharmacy. The Commission on Social Determinants of Health (CSDH) has examined the need for institutional change and the parallel need to address the social causes of poor health. This study explored three potential interventions namely, meaningful information from electronic health records (EHR), social prescribing, and redistributive welfare policies from a person-centered perspective using the CARE (connecting, assessing, responding, and empowering) approach. Economic instruments that immediately redistribute state welfare and reduce income disparity such as direct taxation and conditional cash transfers could be adopted to enable older people with long-term conditions have access to healthcare services. Decreased socioeconomic inequality and unorthodox prescriptive interventions that reduce polypharmacy could mitigate barriers to effectively manage the complexities of multi-morbidity.


Effect of intravenous morphine comedication on bile duct visualization, diameter and volume applying intravenous CT cholangiography in a porcine liver model.
To determine whether intravenous morphine comedication improves bile duct visualization, diameter and/or volume applying intravenous CT cholangiography in a porcine liver model. 12 Landrace pigs underwent intravenous CT cholangiography. Eight minutes after initiation of the contrast material infusion, either morphine sulfate (n = 6 animals) or normal saline (n = 6 animals) was administered. Eighteen consecutive CT scans of the liver were acquired with 2-min intervals starting with initiation of the contrast material infusion. Maximum bile duct visualization scores, diameters and volumes and time to maximum bile duct visualization scores, diameters and volumes were determined. Maximum bile duct visualization scores, diameters and volumes and time to maximum bile duct visualization scores, diameters and volumes were not significantly different when the morphine group was compared to the normal saline group. Maximum bile duct visualization scores ranged between 4.00 ± 0.00 and 2.83 ± 1.47. Maximum bile duct diameters ranged between 6.77 ± 0.40 and 2.10 ± 1.35 mm. Maximum bile duct volume was 16.41 ± 7.33 ml in the morphine group and 16.79 ± 5.65 ml in the normal saline group. Intravenous morphine comedication failed to improve bile duct visualization and to increase bile duct diameter and volume applying CT cholangiography.


[Reproducing and evaluating a rabbit model of multiple organ dysfunction syndrome after cardiopulmonary resuscitation resulted from asphyxia].
To evaluate the reproduction of a model of post resuscitation multiple organ dysfunction syndrome (PR-MODS) after cardiac arrest (CA) in rabbit, in order to provide new methods for post-CA treatment. Thirty-five rabbits were randomly divided into three groups, the sham group (n=5), the 7-minute asphyxia group (n=15), and the 8-minute asphyxia group (n=15). The asphyxia CA model was reproduced with tracheal occlusion. After cardiopulmonary resuscitation (CPR), the ratio of recovery of spontaneous circulation (ROSC), the mortality at different time points and the incidence of systemic inflammatory response syndrome (SIRS) were observed in two asphyxia groups. Creatine kinase isoenzyme (CK-MB), alanine aminotransferase (ALT), creatinine (Cr), glucose (Glu) and arterial partial pressure of oxygen (PaO2) levels in blood were measured in the two asphyxia groups before CPR and 12, 24 and 48 hours after ROSC. The survived rabbits were euthanized at 48 hours after ROSC, and heart, brain, lung, kidney, liver, and intestine were harvested for pathological examination using light microscope. PR-MODS after CA was defined based on the function of main organs and their pathological changes. (1) The incidence of ROSC was 100.0% in 7-minute asphyxia group and 86.7% in 8-minute asphyxia group respectively (P>0.05). The 6-hour mortality in 8-minute asphyxia group was significantly higher than that in 7-minute asphyxia group (46.7% vs. 6.7%, P<0.05), and the mortality of 8-minute asphyxia group at 12 - 48 hours was slightly higher compared with that of 7-minute asphyxia group (all P>0.05). (2) There was a variety of organ dysfunctions in survived rabbits after ROSC, including chemosis, respiratory distress, hypotension, abdominal distension, weakened or disappearance of bowel peristalsis and oliguria. (3) There was no SIRS or associated changes in major organ function in the sham group. SIRS was observed at 12 - 24 hours after ROSC in the two asphyxia groups. CK-MB was increased significantly at 12 hours after ROSC compared with that before asphyxia (7-minute asphyxia group: 786.88±211.84 U/L vs. 468.20±149.45 U/L, 8-minute asphyxia group: 894.88±248.80 U/L vs. 462.11±115.15 U/L, both P<0.05), ALT, Cr and Glu were elevated obviously at 24 hours after ROSC (7-minute asphyxia group ALT: 174.25±36.28 U/L vs. 50.27±9.37 U/L, Cr: 144.25±41.64 μmol/L vs. 67.71±16.47 μmol/L, Glu: 11.21±1.14 mmol/L vs. 5.59±1.10 mmol/L; 8-minute asphyxia group ALT: 205.50±10.61 U/L vs. 51.13±10.37 U/L, Cr: 230.50±88.39 μmol/L vs. 65.93±13.81 μmol/L, Glu: 11.55±0.35 mmol/L vs. 6.41±1.23 mmol/L, all P<0.05), and PaO2 was lowered significantly at 48 hours after ROSC (7-minute asphyxia group: 5.03±0.73 kPa vs. 9.07±1.03 kPa, P<0.05). (4) There were pathological changes in major organ in the survived rabbits at 48 hours after ROSC (only 4 rabbits survived in 7-minute asphyxia group), including infiltration of inflammatory cells, partial cellular degeneration, edema, necrosis and tissue bleeding in major organs. If the SIRS and dysfunction of two or more organ were defined in animals after ROSC, the signs, biochemical markers and nonspecific pathological changes could be accepted to evaluate the PR-MODS.


Transient Obstructive Hydrocephalus due to Intraventricular Hemorrhage: A Case Report and Review of Literature.
Acute transient obstructive hydrocephalus is rare in adults. We describe a patient with intraventricular hemorrhage (IVH) who experienced the delayed development of acute transient hydrocephalus. A 33-year-old man with a previously diagnosed Spetzler-Martin Grade 5 arteriovenous malformation presented with severe headache, which was found to be due to IVH. Forty hours after presentation he developed significant obstructive hydrocephalus due to the thrombus migrating to the cerebral aqueduct, and a ventriculostomy placement was planned. However, shortly thereafter his headache began to improve spontaneously. Within 4 hours after onset the headache had completely resolved, and an interval head CT scan revealed resolution of hydrocephalus. In patients with IVH, acute obstructive hydrocephalus can develop at any time after the ictus. Though a delayed presentation of acute but transient obstructive hydrocephalus is unusual, it is important to be aware of this scenario and ensure that deterioration secondary to thrombus migration and subsequent obstructive hydrocephalus do not occur.