How health economic evaluation (HEE) contributes to decision-making in public health care: the case of Brazil.
The universal access to a health care system for the Brazilian population was established in 1990. Brazil is a country with no tradition in the production and use of health economic evaluation (HEE) to guide decision making in the public health system. It is only within the last two decades that HEEs using a microeconomic approach have appeared in the academic field. On a national level, HEE and Health Technology Assessment (HTA), in a wider sense, were first taken into account in 2003. Two policies deserve to be mentioned - (i) the regulation of medicines in the Brazilian market, and (ii) science, technology and innovation policy. The latter required the fostering of applied research to encourage the application of methods which employ systematic reviews and economic analyses of cost-effectiveness to guide the incorporation of technologies in the Brazilian health care system. The Ministry of Health has initiated the process of incorporating these new technologies on a federal level during the last ten years. In spite of the improvement of HEE methods at Brazilian universities and research institutes, these technologies have not yet reached the governmental bodies. In Brazil, the main challenge lies in the production, interpretation and application of HEE to all technologies within the access scheme(s), and there is limited capacity building. Setting priorities can be the solution for Brazil to be able to perform HEE for relevant technologies within the access scheme(s) while the universal coverage system struggles with a triple burden of disease.


The reading, writing, and arithmetic of the medical literature, part 2: critical evaluation of statistical reporting.
To offer suggestions to help improve clinicians' understanding of the statistical analyses in the literature and their use of these methods in their own medical writings. Literature searches began at the National Library of Medicine's online database and were traced to primary sources. All referenced information in this article was cited from primary sources. Physicians should be able to determine the variables studied and how they were measured, the comparisons that were made, the difference (with 95% confidence interval) between the groups, the exact P value for the difference, the statistical test used in the analysis, whether the data conformed to the assumptions of the test, whether the study had adequate statistical power, and the clinical importance of the difference. Clinicians should know how to interpret statistical results so that they can use medical science to its full extent in treating patients.


Early treatment with C1 esterase inhibitor improves weight but not memory deficits in a rat model of status epilepticus.
Status epilepticus (SE) is a prolonged and continuous seizure that lasts for at least 5 min. An episode of SE in a healthy system can lead to the development of spontaneous seizures and cognitive deficits which may be accompanied by hippocampal injury and microgliosis. Although the direct mechanisms underlying the SE-induced pathophysiology remain unknown, a candidate mechanism is hyperactivation of the classical complement pathway (C1q-C3 signaling). We recently reported that SE triggered an increase in C1q-C3 signaling in the hippocampus that closely paralleled cognitive decline. Thus, we hypothesized that blocking activation of the classical complement pathway immediately after SE may prevent the development of SE-induced hippocampal-dependent learning and memory deficits. Because C1 esterase inhibitor (C1-INH) negatively regulates activation of the classical complement pathway, we used this drug to test our hypothesis. Two groups of male rats were subjected to 1 hr of SE with pilocarpine (280-300 mg/kg, i.p.), and treated with either C1-INH (SE+C1-INH, 20 U/kg, s.c.) or vehicle (SE+veh) at 4, 24, and 48 h after SE. Control rats were treated with saline. Body weight was recorded for up to 23 days after SE. At two weeks post SE, recognition and spatial memory were determined using Novel Object Recognition (NOR) and Barnes maze (BM), respectively, as well as locomotion and anxiety-like behaviors using Open Field (OF). Histological and biochemical methods were used to measure hippocampal injury including cell death, microgliosis, and inflammation. One day after SE, both SE groups had a significant loss of body weight compared to controls (p<0.05). By day 14, the weight of SE+C1-INH rats was significantly higher than SE+veh rats (p<0.05), and was not different from controls (p>0.05). At 14 days post-SE, SE+C1-INH rats displayed higher mobility (distance travelled and average speed, p<0.05) and had reduced anxiety-like behaviors (outer duration, p<0.05) than control or SE+veh rats. In NOR, control rats spent significantly more time exploring the novel object vs. the familiar (p<0.05), while rats in both SE groups spent similar amount of time exploring both objects. During days 1-4 of BM training, the escape latency of the control group significantly decreased over time (p<0.05), whereas that of the SE groups did not improve (p>0.05). Compared to vehicle-treated SE rats, SE+C1-INH rats had increased levels of C3 and microglia in the hippocampus, but lower levels of caspase-3 and synaptic markers. These findings suggest that acute treatment with C1-INH after SE may have some protective, albeit limited, effects on the physiological recovery of rats' weight and some anxiolytic effects, but does not attenuate SE-induced deficits in hippocampal-dependent learning and memory. Reduced levels of caspase-3 suggest that treatment with C1-INH may protect against cell death, perhaps by regulating inflammatory pathways and promoting phagocytic/clearance pathways.


Intrauterine intestinal volvulus with hemoperitoneum presenting as fetal distress at 34 weeks' gestation.
A case of intrauterine intestinal volvulus and hemoperitoneum with symptoms of fetal distress at 34 weeks' gestation is presented. The mechanism of production of late decelerations in this setting is discussed.


[The adaptive possibilities and personal characteristics of boarding school inmates].
About 70% of children and adolescents entering the boarding schools came from the families problematic on the alcoholism and drug addiction where they were subject of the physical and psychological assault. The family ill-being, neglect, lack of consideration for children from the part of their hard drinking parents resulted into the development of mental pathology and pathology of other organs and systems of the body as well. The integral estimates of health of the graduates of boarding schools, their adaptive potential, physical and mental working capacity continue to be very low.


Cerebral hyperperfusion syndrome after intracranial stenting: Case report and systematic review.
Cerebral Hyperperfusion Syndrome (CHS) is an uncommon complication observed after intracranial angioplasty or stenting procedures. Given to the increasing use of new devices for intracranial angioplasty and stenting (INCS), in selected patients with high ischemic stroke risk, an equally increasing knowledge of complications related to these procedures is mandatory.Case description: a 63-year-old man was diagnosed with an hyperperfusion syndrome after percutaneous angioplasty and stenting for severe symptomatic right internal carotid artery (ICA) siphon stenosis. After treatment he complained generalized seizures and respiratory failure. While conventional imaging did not demonstrate any acute brain lesions, Pseudo-Continuous Arterial Spin Labeling (PCASL) Perfusion MRI early documented right hemisphere blood flow increase suggestive for CHS. Monitoring of perfusion changes after INCS could play an important a role in determining patients with high risk of CHS. ASL Perfusion MRI might be used for promptly, early diagnosis of CHS after treatment of severe intracranial artery stenosis.


Renal nephrometry score is associated with urine leak after partial nephrectomy.
• To determine if the RENAL nephrometry score is associated with urine leak after partial nephrectomy for tumours ≤ 7 cm. • Thirty-one patients who developed urine leak after partial nephrectomy between 1998 and 2006 were identified. Each patient was individually matched (1 : 4 by age, gender and surgery date) to 124 patients who had undergone partial nephrectomy but without urine leak. • Associations of RENAL nephrometry scores and each component of the score (Radius; Endophytic; Nearness to collecting system; and Location) with urine leak were evaluated using conditional logistic regression. • Mean tumour size for the 31 patients who developed urine leak was 3.4 cm (median 3.5; range 1.5-5.9). Mean RENAL score was 8 (median 8; range 5-11). • Each unit increase in RENAL score was associated with a 35% increased odds of urine leak (OR 1.35; 95% CI 1.08-1.69; P= 0.009). • On multivariable analysis, tumours that were <50% exophytic (OR 16.65; 95% CI 2.75-100.71; P= 0.002), completely endophytic (OR 17.02; 95% CI 2.88-100.55; P= 0.002), or located at the renal pole (OR 4.34; 95% CI 1.30-14.53; P= 0.017) were associated with urine leak. • If the score attributed to tumour location was reversed (polar location given a higher score), each unit increase in RENAL score was associated with an 89% increased odds of urine leak (OR 1.89; 95% CI 1.40-2.55; P < 0.001). • The RENAL nephrometry score is associated with risk of urine leak after partial nephrectomy. When assessing risk of urine leak, reversal of the score attributed to tumour location may improve risk prediction.


Isoginkgetin, a bioactive constituent from Ginkgo Biloba, protects against obesity-induced cardiomyopathy via enhancing Nrf2/ARE signaling.
Obesity-induced metabolic cardiomyopathy (MC), characterized by lipotoxicity and excessive oxidative stress, emerges as the leading cause of heart failure in the obese patients. Yet, its therapy remains very limited. Here, we demonstrated that isoginkgetin (IGK), a bioactive biflavonoid isolated from medicinal herb Ginkgo Biloba, protected against obesity-induced cardiac diastolic dysfunction and adverse remodeling. Transcriptomics profiling revealed that IGK activated Nrf2 signaling in the heart tissues of the obese mice. Consistent with this observation, IGK treatment increased the nuclear translocation of Nrf2, which in turn trigger the activation of its downstream target genes (e. g. HO-1 and NQO1). In addition, IGK significantly rejuvenated mitochondrial defects in obese heart tissues as evidenced by enhancing mitochondrial respiratory capacity and resisting the collapse of mitochondrial potential and oxidative stress both in vitro and in vivo. Mechanistically, IGK stabilized Nrf2 protein via inhibiting the proteasomal degradation, independent of transcription regulation. Moreover, molecular docking and dynamics simulation assessment demonstrated a good binding mode between IGK and Nrf2/Keap1. Of note, the protective effects conferred by IGK against obesity-induced mitochondrial defects and cardiac dysfunction was compromised by Nrf2 gene silencing both in vitro and in vivo, consolidating a pivotal role of Nrf2 in IGK-elicited myocardial protection against MC. Thus, the present study identifies IGK as a promising drug candidate to alleviate obesity-induced oxidative stress and cardiomyocyte damage through Nrf2 activation, highlighting the therapeutic potential of IGK in ameliorating obesity-induced cardiomyopathy.


First detection of Psittacid alphaherpesvirus 5 and coinfection with beak and feather disease virus in naturally infected captive ringneck parakeets (Psittacula krameri) in Brazil.
This study describes a case report in captive rose-ringed parakeets (Psittacula krameri) that developed clinical signs and eventually died after introducing new birds without quarantine. Bronchopneumonia and airsacculitis with syncytial cells associated with intranuclear inclusion bodies were found. Herpesvirus was detected in lungs and liver by PCR, and a nearly complete genome sequence of a Psittacid alphaherpesvirus 5 was obtained from the lung of a bird. Metagenomic analysis also identified beak and feather disease virus in the same samples. The study also highlights the importance of quarantine for avoiding the introduction of new diseases in captive aviaries.


Headache, menstruation and combined oral contraceptives: a diary study in 184 women with migraine.
Half of female migraineurs in childbearing age use combined oral contraceptives (COCs), but the influence of COCs on perimenstrual migraine is still unclear. We therefore aimed to analyze the risk of occurrence and persistence (i.e. presence for more than 1 day) of headache and migraine before and during menstruation in women with migraine, comparing users of COCs to non-users. We included 184 women with at least 1 day of menstruation recorded in a 90-day diary. We differentiated between (a) the 2 days before menstruation, (b) the first 3 days of menstruation and (c) the remaining days of menstruation and analyzed subgroups of women with (n=82) and without (n=102) COCs. In both groups, risk of any headache as well as that of migraine was highest during the first 3 days of menstruation with a hazard ratio of 1.9 and 2.1 for non-users and 2.1 and 2.2 for users. Although use of COCs showed no statistically significant overall effect, users were at higher risk for any headache premenstrually and non-users at higher risk for migraine on days 4+ of menstruation. In conclusion, use of COCs exerts only subtle differences on the course of perimenstrual migraine in menstruating women with migraine.


Morphological asymmetries of the tectum opticum in the pigeon.
Pigeons are visually lateralized with a dominance of the right eye. Due to the virtually complete decussation of the optic nerves in birds, a right eye superiority probably depends on a left brain hemisphere dominance. The aim of the present study was to analyze whether morphological asymmetries in the cross-sectional area of perikarya can be found within the retina and the optic tectum. With an image-analyzing system the cross-sectional areas of the somata of retinal ganglion cells and tectal neurons were measured in the left and the right side under blind conditions. The results reveal significant morphological left-right differences, with cells in superficial layers 2-12 being larger on the left side while neurons in laminae 13-15 have larger somata in the right tectum. No retinal asymmetries could be revealed. Since pigeon embryos keep their head turned to the right within the egg, such that the right eye is stimulated by light shining through the shell, it is possible that the morphological asymmetries at the tectal level are induced by left-right differences in prehatching photic stimulation. This embryonic sensory asymmetry might lead to a higher activity level of right eye ganglion cells and to a larger amount of released neurotrophins in the left tectum. This in turn could exert the morphological effects on soma sizes in the superficial retinorecipient layers.


Tumor-infiltrating lymphocytes: apparently good for melanoma patients. But why?
Tumor-infiltrating T lymphocytes (TILs) are observed in a number of human primary or metastatic tumors. Recently, gene expression profiling experiments suggested that the presence of T cells in metastatic melanomas before vaccinating the patients with tumor antigens could be a biomarker for clinical benefit from the vaccines. In this context, we review results pertaining to TILs in human melanomas, their prognostic value, and some possible reasons why their presence could help in selecting melanoma patients for vaccination against tumor-specific antigens.


Structure and action of heteronemertine polypeptide toxins. Amino acid sequence of Cerebratulus lacteus toxin B-II and revised structure of toxin B-IV.
The primary structure of Cerebratulus lacteus toxin B-II has been investigated by automated Edman degradation of the reduced, carboxymethylated protein and of tryptic peptides derived from the maleylated protein. As a result of these studies, the identity of all 55 amino acid residues in the polypeptide chain has been unambiguously determined. Hydroxyproline, an amino acid not normally found in nonfibrous proteins, occupies position 10 of toxin B-II. The sequence analysis of B-II led us to re-examine the sequence of Cerebratulus toxin B-IV. The revised structure of toxin B-IV is presented herein. Like B-II, toxin B-IV contains hydroxyproline at position 10 of its sequence. Comparison of the sequences of toxins B-II and B-IV reveals a high degree of homology between these two polypeptides, particularly within the NH2-terminal two-thirds of each chain.


Reprocessable Thermoset Soft Actuators.
Widely used traditional thermosets are good candidates for construction of 3D soft actuators because of their excellent stability; however, it is generally acknowledged that they cannot be reprocessed. The time-temperature equivalence principle enables reprocessing of traditional liquid crystalline epoxy thermosets (LCETs) into 3D soft actuators. Even though the transesterification reaction of LCETs is extremely slow, it is fast enough to induce a topology rearrangement and subsequent reprocessing when prolonging the transesterification time according to aforementioned principle. Therefore, LCETs can be aligned by a simple procedure. The alignment is quite stable at high temperature and remains after more than 1000 heating-cooling actuation cycles. The resulting 3D soft actuators are remouldable, reprogrammable, reconfigurable, weldable, self-healable, recyclable, and stable, which is impossible for any traditional thermosets and is therefore a compelling advance in terms of the applications open to 3D soft actuators.


Vasculoprotective Potential of Baicalein in Angiotensin II-Infused Abdominal Aortic Aneurysms through Inhibiting Inflammation and Oxidative Stress.
Aortic wall inflammation, abnormal oxidative stress and progressive degradation of extracellular matrix proteins are the main characteristics of abdominal aortic aneurysms (AAAs). The nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome dysregulation plays a crucial role in aortic damage and disease progression. The first aim of this study was to examine the effect of baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one) on AAA formation in apolipoprotein E-deficient (ApoE-/-) mice. The second aim was to define whether baicalein attenuates aberrant vascular smooth muscle cell (VSMC) proliferation and inflammation in VSMC culture. For male ApoE-/- mice, a clinically relevant AAA model was randomly divided into four groups: saline infusion, baicalein intraperitoneal injection, Angiotensin II (Ang II) infusion and Ang II + baicalein. Twenty-seven days of treatment with baicalein markedly decreased Ang II-infused AAA incidence and aortic diameter, reduced collagen-fiber formation, preserved elastic structure and density and prevented smooth muscle cell contractile protein degradation. Baicalein inhibited rat VSMC proliferation and migration following the stimulation of VSMC cultures with Ang II while blocking the Ang II-inducible cell cycle progression from G0/G1 to the S phase in the synchronized cells. Cal-520 AM staining showed that baicalein decreased cellular calcium in Ang II-induced VSMCs; furthermore, a Western blot assay indicated that baicalein inhibited the expression of PCNA and significantly lowered levels of phospho-Akt and phospho-ERK, along with an increase in baicalein concentration in Ang II-induced VSMCs. Immunofluorescence staining showed that baicalein pretreatment reduced NF-κB nuclear translocation in Ang II-induced VSMCs and furthered the protein expressions of NLRP3 while ASC and caspase-1 were suppressed in a dose-dependent manner. Baicalein pretreatment upregulated Nrf2/HO-1 signaling in Ang II-induced VSMCs. Thus, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining showed that its reactive oxygen species (ROS) production decreased, along with the baicalein pretreatment. Our overall results indicate that baicalein could have therapeutic potential in preventing aneurysm development.


p21WAF1/CIP1 gene transcriptional activation exerts cell growth inhibition and enhances chemosensitivity to cisplatin in lung carcinoma cell.
Non-small-cell lung carcinomas (NSCLCs) exhibit poor prognosis and are usually resistant to conventional chemotherapy. Absence of p21WAF1/CIP1, a cyclin-dependent kinase (cdk) inhibitor, has been linked to drug resistance in many in vitro cellular models. RNA activation (RNAa) is a transcriptional activation phenomena guided by double-strand RNA (dsRNA) targeting promoter region of target gene. In this study, we explored the effect of up-regulation of p21 gene expression on drug-resistance in A549 non-small-cell lung carcinoma cells by transfecting the dsRNA targeting the promoter region of p21 into A549 cells. Enhanced p21 expression was observed in A549 cells after transfection of dsRNA, which was correlated with a significant growth inhibition and enhancement of chemosensitivity to cisplatin in A549 cells in vitro. Moreover, in vivo experiment showed that saRNA targeting the promoter region of p21 could significantly inhibit A549 xenograft tumor growth. These results indicate that p21 plays a role in lung cancer drug-resistance process. In addition, this study also provides evidence for the usage of saRNA as a therapeutic option for up-regulating lower-expression genes in lung cancer.


N-hydroxy-N'-aminoguanidines as anti-cancer lead molecule: QSAR, synthesis and biological evaluation.
The intrinsic pharmacophore model (r(pred)(2) and r(m)(2) of 0.858 and 0.725) has been developed and used as a query to screen in-house built library based on N-hydroxy-N'-aminoguanidine (HAG) analogs. The pharmacophoric modeled based HITs were synthesized and evaluated for anticancer activity and cytotoxicity. One of the compounds (15) appeared as promising lead candidate with an IC(50) value of 11 μM yielded in HL-60 promyelocytic leukemia cells. Compound 15 reveals significantly lower cytotoxicity against HeLa and Vero cell with CC(50) values of more than 100 μM.


Development and verification of a discriminate algorithm for diagnosing post-neurosurgical bacterial meningitis-A multicenter observational study.
To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF)-based routine clinical examinations for post-neurosurgical bacterial meningitis (PNBM) in multicenter post-neurosurgical patients. The diagnostic accuracies of routine examinations to distinguish between PNBM and post-neurosurgical aseptic meningitis (PNAM) were evaluated by determining the values of the area under the curve (AUC) of the receiver operating characteristic curve in a retrospective analysis of post-neurosurgical patients in four centers. An algorithm was constructed using the logistic analysis as a classical method to maximize the capacity for differentiating the two classes by integrating the measurements of five variables. The AUC value of this algorithm was 0.907, which was significantly higher than those of individual routine blood/CSF examinations. The predicted value from 70 PNBM patients was greater than the cutoff value, and the diagnostic accuracy rate was 75.3%. The results of 181 patients with PNAM showed that 172 patients could be correctly identified with specificity of 95.3%, while the overall correctness rate of the algorithm was 88.6%. Routine biomarkers such as CSF/blood glucose ratio (C/B-Glu), CSF lactate (C-Lac), CSF glucose concentration (C-Glu), CSF leukocyte count (C-Leu), and blood glucose concentration (B-Glu) can be used for auxiliary diagnosis of PNBM. The multicenter retrospective research revealed that the combination of the five abovementioned biomarkers can effectively improve the efficacy of the PNBM diagnosis.


Naturally occurring layered mineral franckeite with anisotropic Raman scattering and third-harmonic generation responses.
Vertically stacked van der Waals (vdW) heterostructures have introduced a unique way to engineer optical and electronic responses in multifunctional photonic and quantum devices. However, the technical challenges associated with the artificially fabricated vertical heterostructures have emerged as a bottleneck to restrict their proficient utilization, which emphasizes the necessity of exploring naturally occurring vdW heterostructures. As one type of naturally occurring vdW heterostructures, franckeite has recently attracted significant interest in optoelectronic applications, but the understanding of light-matter interactions in such layered mineral is still very limited especially in the nonlinear optical regime. Herein, the anisotropic Raman scattering and third-harmonic generation (THG) from mechanically exfoliated franckeite thin flakes are investigated. The observed highly anisotropic Raman modes and THG emission patterns originate from the low-symmetry crystal structure of franckeite induced by the lattice incommensurability between two constituent stacked layers. The thickness-dependent anisotropic THG response is further analyzed to retrieve the third-order nonlinear susceptibility for franckeite crystal. The results discussed herein not only provide new insights in engineering the nonlinear light-matter interactions in natural vdW heterostructures, but also develop a testbed for designing future miniaturized quantum photonics devices and circuits based on such heterostructures.


An altered microbiome in urban coyotes mediates relationships between anthropogenic diet and poor health.
Generalist species able to exploit anthropogenic food sources are becoming increasingly common in urban environments. Coyotes (Canis latrans) are one such urban generalist that now resides in cities across North America, where diseased or unhealthy coyotes are frequently reported in cases of human-wildlife conflict. Coyote health and fitness may be related to habitat use and diet via the gut microbiome, which has far-reaching effects on animal nutrition and physiology. In this study, we used stomach contents, stable isotope analysis, 16S rRNA gene amplicon sequencing, and measures of body condition to identify relationships among habitat use, diet, fecal microbiome composition, and health in urban and rural coyotes. Three distinct relationships emerged: (1) Urban coyotes consumed more anthropogenic food, which was associated with increased microbiome diversity, higher abundances of Streptococcus and Enterococcus, and poorer average body condition. (2) Conversely, rural coyotes harbored microbiomes rich in Fusobacteria, Sutterella, and Anaerobiospirillum, which were associated with protein-rich diets and improved body condition. (3) Diets rich in anthropogenic food were associated with increased abundances of Erysipelotrichiaceae, Lachnospiraceae, and Coriobacteriaceae, which correlated with larger spleens in urban coyotes. Urban coyotes also had an increased prevalence of the zoonotic parasite Echinococcus multilocularis, but there were no detectable connections between parasite infection and microbiome composition. Our results demonstrate how the consumption of carbohydrate-rich anthropogenic food by urban coyotes alters the microbiome to negatively affect body condition, with potential relationships to parasite susceptibility and conflict-prone behavior.


Factors Influencing Discussion of Cancer Genetic Testing with Health-Care Providers in a Population-Based Survey.
Discussion of cancer genetic testing with health-care providers (HCPs) is necessary to undergo testing to inform cancer risk assessment and prevention. Given the rapid evolution in genetic testing practice in oncology, we describe the current landscape of population-level cancer genetic testing behaviors. A questionnaire including items regarding discussion of cancer genetic testing with HCPs was administered to a nonprobability sample (N = 2,029) of the Texas population. Overall, 11% of respondents discussed cancer genetic testing with HCPs. In multivariable analysis, discussion was significantly related to having a personal history of breast/ovarian/colon cancer (OR = 11.57, 95% CI = 5.34-25.03), personal history of other cancer (OR = 3.18, 95% CI = 1.69-5.97), and health information-seeking behaviors (OR = 1.73, 95% CI = 1.12-2.66). Surprisingly, respondents who believed that inherited predispositions in addition to other modifiable risk factors cause cancer were less likely to discuss genetic testing compared to those who did not believe that inherited cancer predispositions cause cancer (OR = 0.54, 95% CI = 0.36-0.79). The high discussion rate may be attributed to increased public awareness of genetic testing and adoption of more inclusive clinical genetic testing guidelines. The findings suggest that efforts to increase public awareness of the utility of genetic testing on personalized cancer risk assessment and cancer prevention are needed.


Chronic vascular diseases in cuba: strategies for 2015.
Chronic diseases are Cuba's number one health problem, causing 90% of all deaths. The top three killers (in order) are: heart disease, cancer and cerebrovascular diseases, which together account for nearly 60% of all deaths.


The permeability barrier in the epidermis of the grass snake during the resting stage of the sloughing cycle.
Tracer and freeze-fracture replication techniques show that there are two morphologically and topographically distinct permeability barriers in the epidermis of the grass snake. Tight junctions interconnect the apico-lateral plasma membranes of the uppermost living cells, establishing an ionic or osmotic gradient between the stratum germinativum and alpha layer. The second barrier is formed by intercellular lipid sheets in the overlying mesos layer, which are very similar to the barrier found in the stratum corneum of mammals.


Appendicorectal fistula with a novel solution: First case report and review of the literature.
Appendicorectal fistula can be a cause of chronic abdominal pain, forming years after an occult episode of appendicitis. It can be diagnosed with Colonoscopy and Magnetic Resonance Imaging, and successfully treated surgically with laparoscopic appendicectomy and stapled segmental cuff resection of the rectum.


Unusual presentation of central nervous system cryptococcal infection in an immunocompetent patient.
The imaging findings of cryptococcosis affecting the brain in immunocompetent patients can be different from the more commonly described findings in immunocompromised patients. We report a case of an extremely unusual MR appearance of central nervous system cryptococcosis in a 49-year-old immunocompetent man.


Chronic cold exposure modulates genes related to feeding and immune system in Nile tilapia (Oreochromis niloticus).
Nile tilapia is the fourth most produced species in the global aquiculture panorama. This species requires water temperatures higher than 16 °C to grow and survive, and so, little is known about the effects of low temperatures on genes related to food intake and inflammatory responses. This study brought insights about the modulation of genes in different tissues of Nile tilapia chronically exposed to low temperatures. Thus, sixty animals were divided in two experimental groups: a control group in which the animals remained at the optimum temperature of 24 °C; and an exposed to cold group, in which a decrease in the water temperature was applied until reaching 15 °C. These conditions were maintained for 28 days. Blood samples were collected for flow cytometry analysis, while brain, spleen, liver, and kidney tissues were collected for total RNA extraction, followed by quantitative PCR (RT-qPCR). For genes related to feeding process pathway, it was observed an upregulation in pyy and a downregulation of npy and cart gene expression. Also, pro-inflammatory cytokine genes were modulated in the spleen, kidney and liver with a higher expression of il-1b and tnfα and a reduction in the il-8 and nf-κβ gene expressions in the group exposed to 15 °C. The fish exposed to cold presented higher serum cortisol levels than the ones from control group. The blood cell analysis showed a lower level of membrane fluidity and a higher DNA fragmentation and cell disruption in the group exposed to cold. These findings suggest an important effect of a stressful situation in the tilapia organism due to cold exposure. This study brings insights on tilapia wellbeing under low temperature stress. It can be a first step to understanding the appropriate way to cope with cold impacts on aquaculture.


Bile-Based Cell-Free DNA Analysis Is a Reliable Diagnostic Tool in Pancreatobiliary Cancer.
Currently available serum biomarkers for pancreatobiliary cancers lack sensitivity and specificity and ultimate diagnosis still requires invasive procedures for histological confirmation. The detection of tumor-specific genetic aberrations with utilization of cell free DNA (cfDNA) is a less invasive approach than traditional tissue biopsies; however, it has not been implemented into clinical routine. In this study, we investigated bile as a liquid biopsy source in pancreatobiliary cancers and compared its potential as cell-free DNA source to plasma. Blood (n = 37) and bile (n = 21) samples were collected from patients affected by pancreatic ductal adenocarcinoma (PDAC) and extrahepatic cholangiocarcinoma (CCA) or with non-malignant biliary obstructions (blood n = 16; bile n = 21). Panel-based next generation sequencing (NGS) and digital droplet PCR (ddPCR) were applied for tumor mutation profiling. NGS results from matched tumor tissues (n = 29) served as comparison. Sequencing of cfDNA from bile resulted in detection of 96.2% of the pathogenic tumor mutations found in matched tissue samples. On the other hand, only 31.6% of pathogenic tumor mutations found in tissue could be detected in plasma. In a direct comparison, only half of the mutations detected in bile cfDNA were concordantly detected in plasma from the same patients. Panel NGS and ddPCR displayed comparable sensitivity. In conclusion, bile is a suitable source of cfDNA for the diagnosis of pancreatobiliary cancer and performs more reliably than plasma. Although primary diagnosis still requires histologic confirmation, bile-derived cfDNA could offer an alternative if tissue sampling is not feasible and might allow less invasive disease monitoring.


Elevation of 11β-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: evidence for an intergenerational effect of maternal trauma exposure.
Adult offspring of Holocaust survivors comprise an informative cohort in which to study intergenerational transmission of the effects of trauma exposure. Lower cortisol and enhanced glucocorticoid sensitivity have been previously demonstrated in Holocaust survivors with PTSD, and in offspring of Holocaust survivors in association with maternal PTSD. In other work, reduction in the activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), which inactivates cortisol, was identified in Holocaust survivors in comparison to age-matched, unexposed Jewish controls. Therefore, we investigated glucocorticoid metabolism in offspring of Holocaust survivors to evaluate if similar enzymatic decrements would be observed that might help to explain glucocorticoid alterations previously shown for Holocaust offspring. Holocaust offspring (n=85) and comparison subjects (n=27) were evaluated with clinical diagnostic interview and self-rating scales, and asked to collect a 24-h urine sample from which concentrations of cortisol and glucocorticoid metabolites were assayed by GCMS. 11β-HSD-2 activity was determined as the ratio of urinary cortisone to cortisol. Significantly reduced cortisol excretion was observed in Holocaust offspring compared to controls (p=.046), as had been shown for Holocaust survivors. However, 11β-HSD-2 activity was elevated for offspring compared to controls (p=.008), particularly among those whose mothers had been children, rather than adolescents or adults, during World War II (p=.032). The effect of paternal Holocaust exposure could not be reliably investigated in the current sample. The inverse association of offspring 11β-HSD-2 activity with maternal age at Holocaust exposure is consistent with the influence of glucocorticoid programming. Whereas a long standing reduction in 11β-HSD-2 activity among survivors is readily interpreted in the context of Holocaust related deprivation, understanding the directional effect on offspring will require replication and further exploration.


A fermented formula in pre-term infants: clinical tolerance, gut microbiota, down-regulation of faecal calprotectin and up-regulation of faecal secretory IgA.
Intestinal bacterial colonisation in pre-term infants is delayed compared with full-term infants, leading to an increased risk of gastrointestinal disease. Modulation of colonisation through dietary supplementation with probiotics or prebiotics could decrease such a risk. The present study evaluated clinical tolerance, the effects on gut microbiota, and inflammatory and immunological mucosal responses to an infant formula adapted for pre-term infants that included in its manufacturing process a fermentation step with two probiotic strains, Bifidobacterium breve C50 and Streptococcus thermophilus 065, inactivated by heat at the end of the process. A total of fifty-eight infants (gestational age: 30-35 weeks), fed either the fermented pre-term formula or a standard pre-term formula, were followed up during their hospital stay. Clinical tolerance, faecal microbiota using a culture and a culture-independent method (temporal temperature gel electrophoresis), faecal calprotectin and secretory IgA were analysed weekly. No difference was observed regarding anthropometric data and digestive tolerance, except for abdominal distension, the incidence of which was lower in infants fed the fermented formula for 2 weeks. Bacterial colonisation was not modified by the type of feeding, particularly for bifidobacteria. Faecal calprotectin was significantly lower in infants fed the fermented formula for 2 weeks, and secretory IgA increased with both mother's milk and the fermented formula. The fermented formula was well tolerated and did not significantly modulate the bacterial colonisation but had benefits on inflammatory and immune markers, which might be related to some features of gastrointestinal tolerance.


Characterization of complement C3 as a marker of alpha-amanitin toxicity by comparative secretome profiling.
In the human body, proteins secreted into peripheral blood vessels are known as the secretome, and they represent the physiological or pathological status of cells. The unique response of cells to toxin exposure can be confirmed via secretome analysis, which can be used to discover toxic mechanisms or exposure markers. Alpha-amanitin (α-AMA) is the most widely studied amatoxin and inhibits transcription and protein synthesis by directly interacting with RNA polymerase II. However, secretory proteins released during hepatic failure caused by α-AMA have not been fully characterized. In this study, we analyzed the secretome of α-AMA-treated Huh-7 cells and mice using a comparative proteomics technique. Overall, 1440 and 208 proteins were quantified in cell media and mouse serum, respectively. Based on the bioinformatics results for the commonly downregulated proteins in cell media and mouse serum, we identified complement component 3 (C3) as a marker for α-AMA-induced hepatotoxicity. Through western blot in cell secretome and C3 ELISA assays in mouse serum, we validated α-AMA-induced downregulation of C3. In conclusion, using comparative proteomics and molecular biology techniques, we found that α-AMA-induced hepatotoxicity reduced C3 levels in the secretome. We expect that this study will aid in identifying new toxic mechanisms, therapeutic targets, and exposure markers of α-AMA-induced hepatotoxicity. The online version contains supplementary material available at 10.1007/s43188-022-00163-z.


Coenzyme Q10 and niacin mitigate streptozotocin- induced diabetic encephalopathy in a rat model.
Diabetic encephalopathy is an important complication of diabetes characterized by cognitive impairment, neurochemical and structural abnormalities. This study aimed to investigate the effect of coenzyme Q10 (CoQ10) and niacin as well as their combination in the treatment of encephalopathy associated with streptozotocin (STZ)- induced diabetes in rats. Glibenclamide (reference diabetic drug) and donepezil hydrochloride (acetylcholinesterase inhibitor) were also evaluated. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). One month after STZ injection, diabetic rats were treated with the aforementioned drugs for two weeks. The evaluation was done through measuring glucose level, total antioxidant capacity (TAC), interleukin 6 (IL6), DNA degradation as well as serotonin and noradrenaline as neurotransmitters. The present data illustrated that combining CoQ10 and niacin exhibiting the most potent effect in improving the measured parameters and ameliorating some of diabetes complications.


Brain natriuretic peptide in hemodialysis patients: predictive value for hemodynamic change during hemodialysis and cardiac function.
Though brain natriuretic peptide (BNP) is widely used as a clinical marker of cardiac function, there is considerable confusion in the interpretation of its value in hemodialysis (HD) patients whose BNPs are often elevated without cardiac diseases. The aim of the present study is to examine the predictive value of BNP for blood pressure (BP) fall during HD and cardiac function. Subjects consisted of 205 (160 males, 45 females; age 66.5 +/- 10.5 years) consecutive uremic patients requiring maintenance HD who were admitted to our hospital during 2001-2004. One hundred and eleven cases had a history of ischemic heart disease. We measured BNP in all cases and collected clinical data including age, sex, duration of HD, blood examination and echocardiography. BNP of all 205 cases ranged from 6 to 16,097 pg/ml (median 831). During HD, the average BP change was -24.5 +/- 20.5 mm Hg, and 111 cases showed a systolic BP reduction >20 mm Hg. BNP did not predict the degree of BP fall. After adjusting confounding factors, the presence of ischemic heart disease, ultrafiltration rate, systolic BP before HD and serum sodium concentration showed a significant correlation with BP change (t = -2.84, -2.76, -4.68 and 2.90; p = 0.005, <0.01, <0.0001 and <0.005, respectively). In relation to echocardiographic indices, BNP >785 pg/ml could predict left ventricular dysfunction (fractional shortening of the left ventricle <30%, sensitivity 73%, specificity 65%). The level of BNP could not predict BP fall during HD. However, BNP is a good indicator of cardiac function even in uremic patients.


Mapping ecological space quality changes for ecological management: A case study in the Pearl River Delta urban agglomeration, China.
Compiling information concerning changes in ecological space quality (ESQ) is imperative for urban management and restoration, as proper management promotes sustainable development. Most previous studies have lacked a comprehensive model for evaluating ESQ and are thus unable to provide effective support for decision-makers. Based on the purpose of policy and needs of the public, this paper constructs a comprehensive adaptive evaluation model for mapping ESQ using the Pearl River Delta (PRD) urban agglomeration as an example, and the analysis uncovers the driving forces of urbanization indicators of ESQ change. From 2000 to 2017, the overall ESQ was considered as good, but the overall value decreased slightly, from 52.8 to 51.5. ESQ in the central PRD exhibited a notable downward trend, while coastal cities exhibited an upward trend. There was an approximate negative correlation between ESQ and the urbanization indexes, except for education level and the proportion of primary industry. In the PRD, rural population density, the proportion of primary industry, and education level were the important drivers of magnitude and direction in most cities, but their impacts differed across cities. The ecological management lacked control of in areas good and moderate ESQ, and this was the main factor resulting in the decline of regional ESQ. By quantifying ESQ and the spatially explicit urbanization drivers, the potential for ecological management in the urban agglomeration is also discussed.


Digital innovations for retinal care in diabetic retinopathy.
The purpose of this review is to examine the applications of novel digital technology domains for the screening and management of patients with diabetic retinopathy (DR). A PubMed engine search was performed, using the terms "Telemedicine", "Digital health", "Telehealth", "Telescreening", "Artificial intelligence", "Deep learning", "Smartphone", "Triage", "Screening", "Home-based", "Monitoring", "Ophthalmology", "Diabetes", "Diabetic Retinopathy", "Retinal imaging". Full-text English language studies from January 1, 2010, to February 1, 2022, and reference lists were considered for the conceptual framework of this review. Diabetes mellitus and its eye complications, including DR, are particularly well suited to digital technologies, providing an ideal model for telehealth initiatives and real-world applications. The current development in the adoption of telemedicine, artificial intelligence and remote monitoring as an alternative to or in addition to traditional forms of care will be discussed. Advances in digital health have created an ecosystem ripe for telemedicine in the field of DR to thrive. Stakeholders and policymakers should adopt a participatory approach to ensure sustained implementation of these technologies after the COVID-19 pandemic. This article belongs to the Topical Collection "Diabetic Eye Disease", managed by Giuseppe Querques.


Safety of a prehospital emergency medical services protocol for an alternative destination for pediatric behavioral emergencies in Alameda County.
Pediatric patients with behavioral health emergencies (BHEs) are often transported to an emergency department (ED) by emergency medical services (EMS), despite having no physical medical complaints, to await psychiatric evaluation and treatment. This process leads to significant delays in their care. We examined the safety of directly transporting pediatric patients with BHEs from the field to an alternative destination of a psychiatric emergency service (PES) facility using an EMS protocol. A retrospective review from November 1, 2011, to November 1, 2016, was conducted for pediatric EMS encounters using EMS data from Alameda County, California. Our primary outcome was the safety of a prehospital alternative destination protocol. We identified the proportion of patients who required retransport to an ED within 24 h after arriving at PES (defined as a failed diversion). We also describe the mortality of all patients being transported for a BHE. There were 38,241 total pediatric encounters, with 20.1% for BHEs. A total of 3122 (41%) BHE encounters met protocol criteria and were transported directly to the PES. Only 16 (0.5%) patients had a secondary transport (failed diversion) to an ED within 24 h of arrival. No patients with a BHE transported to the PES died within 30 days of the EMS encounter. Death and adverse clinical outcomes are extremely rare in pediatric patients using a prehospital alternative destination protocol. This information could significantly improve the care of children with BHEs.


Microdissection of peripheral nerve: collagen and lipid distribution with morphological correlation.
Peripheral nerve is a complex tissue composed of endoneurial fascicles surrounded by perineurium and epineurium. We separated endoneurium from peri- and epineurium in human sural nerves by "endoneurial plucking", a method of microdissection. Endoneurial contents (axons, myelin sheaths, Schwann cells, vessels, and interstitial collagen) were cleanly separated in high yield from enveloping connective tissue, by both microscopic and biochemical criteria. Most of the nerve sulfatide and unesterified sterol was found in the endoneurial fraction while most of the collagen was in the peri-epineurial fraction. This microdissection method should prove useful in biochemical investigations of peripheral nerve.


Development and validation of the smartphone addiction risk children questionnaire (SARCQ).
Smartphone abuse interferes with all activities in daily life. Young people who tend to have a smartphone addiction (SA) also have social, familiar and academic problems. Furthermore, smartphone provides immediate access to communication as well as avoids experiencing social anxiety. This research aims to evaluate the factorial structure of Smartphone Addiction Risk Children Questionnaire (SARCQ), a specific questionnaire created to assess the risk of SA in primary school children (8-11 years). An exploratory factor analysis before and a confirmatory factor analysis after were performed in order to establish the factorial structure of the questionnaire. Results showed a two-factor structure explaining 49.30% of total variance. The outstanding dimensions are: "I'm not afraid with you" (INAWY) and "Linus blanket" (LB). SARCQ will be useful to assess the risk of SA in childhood in order to operate early effective therapeutic interventions.


Enteral feeding in the critically ill: are nursing practices contributing to hypocaloric feeding?
Enteral feeding is the preferred method of nutritional support for the critically ill; however, a significant number of these patients are under-fed. It is possible that common nursing practices associated with the delivery of enteral feeding may contribute to under-feeding although there is little data available describing nursing practice in this area. A descriptive survey-based design was used to explore the enteral feeding practices of 376 critical care nurses (response rate 50.5%). Participants completed a 57-item survey that focused on general enteral feeding practice and the management of feeding intolerance and complications. The enteral feeding practice of critical care nurses varied widely and included some practices that could contribute to under-feeding in the critically ill. Practices associated with the measurement of gastric residual volumes (GRV) were identified as the most significant potential contributor to under-feeding. GRV measurements were commonly used to assess feeding tolerance (n = 338; 89.9%) and identified as a reason to delay feeding (n = 246; 65.4%). Delayed gastric emptying was frequently managed by prokinetic agents (n = 237; 63%) and decreasing the rate of feeding (n = 247; 65.7%) while nursing measures, such as changing patient position (n = 81; 21.5%) or checking tube placement (n = 94; 25%) were less frequently reported. The findings of this survey support the contention that nursing practices associated with the delivery of enteral feeds may contribute to under-feeding in the critically ill patient population.


Invasive potential of tropical fruit flies in temperate regions under climate change.
Tropical fruit flies are considered among the most economically important invasive species detected in temperate areas of the United States and the European Union. Detections often trigger quarantine and eradication programs that are conducted without a holistic understanding of the threat posed. Weather-driven physiologically-based demographic models are used to estimate the geographic range, relative abundance, and threat posed by four tropical tephritid fruit flies (Mediterranean fruit fly, melon fly, oriental fruit fly, and Mexican fruit fly) in North and Central America, and the European-Mediterranean region under extant and climate change weather (RCP8.5 and A1B scenarios). Most temperate areas under tropical fruit fly propagule pressure have not been suitable for establishment, but suitability is predicted to increase in some areas with climate change. To meet this ongoing challenge, investments are needed to collect sound biological data to develop mechanistic models to predict the geographic range and relative abundance of these and other invasive species, and to put eradication policies on a scientific basis.


Minor Papillary Relief in a Type IA Choledochal Cyst: A Case Report and Review of the Literature.
Choledochal cysts are an anatomical conundrum as they present with nonspecific symptoms generally delaying diagnosis and treatment. Its lag time remains critical, as cholangiocarcinoma, a fatal sequelae, contributes to its morbidity and mortality. Herein, we present a case of a type 1A choledochal cyst. We hope that its review on presentation, classification system, diagnosis, and management prevent complications and cataclysmic results.


Antibodies to A19 and Bw35 complexes of human leukocyte antigens are present in infertile subjects with sperm antibodies.
Sera and secretions from 100 couples with unexplained infertility were tested for sperm antibodies by cytotoxicity and passive hemagglutination and also for antibodies to human leukocyte antigen (HLA) by cytotoxicity assays. Lymphocytes of the study subjects were typed for 61 HLA-A and B alleles. Thirteen of 30 (43%) men with sperm autoimmunity also had HLA antibodies in their serum and/or seminal plasma samples, in contrast to 2 of 35 (6%) nonautoimmune males (P = 0.0003). Twenty-five of 35 (71%) sperm antibody-positive infertile women had HLA antibodies in their sera and/or secretions, while only 7 of 31 (23%) women without sperm antibodies were positive (P = 0.00007). Antibodies to HLA-A19 (A26, A29, AW30, AW31, AW32, AW33, and AW34) and Bw35 (B5, B15, B17, and B18) complexes were present in 19 of 22 (86%) infertile men and 44 of 48 (92%) infertile women positive for HLA antibodies (P less than 0.01). The presence of antibodies to HLA-A19 and/or Bw35 in the infertile subjects did not correlate with the presence of HLA-A19 and/or Bw35 in the husbands. The presence of antibodies to HLA-A19 and/or Bw35 in the cervical mucus of the infertile women correlated with their presence in the seminal plasma of their husbands. It is suggested that antibodies to sperm antigens cross-reactive with HLA-A19 and/or Bw35 may be relevant to infertility.


Sensitive biosensor array using surface plasmon resonance on metallic nanoslits.
Chip-based biosensor arrays for label-free and high-throughput detection were fabricated and tested. The sensor array was composed of a 150-nm-thick, 50-nm-gap, and 600-nm-period gold nanoslits. Each array size was 100 mumx100 mum. A transverse-magnetic polarized wave in these metallic nanostructures generated resonant surface plasmons at a wavelength of about 800 nm in a water environment. Using the resonant wavelength shift in the nanoslit array, we achieved detection sensitivity up to 668 nm per refractive index unit, about 1.7 times larger than that reported on an array of nanoholes. An antigen-antibody interaction experiment in an aqueous environment verified the sensitivity in a surface binding event.


Induction of spheroid cytoplasmic bodies in a rat muscle by local tetanus.
The term "cytoplasmic body" or "spheroid body" myopathy refers to a heterogeneous group of familial or sporadic diseases characterized primarily by the presence of abundant spheroid or cytoplasmic bodies in the muscles. The morphogenesis of these inclusions remains unclear. This article describes the induction and evolution of spheroid cytoplasmic bodies (SCBs) in the rat plantaris muscle (PL) with local tetanus, which was induced in rats by the injection of a minute amount of tetanus toxin. In contrast to the tetanized soleus muscle (SOL), which developed core fibers (central cores, minicore, target fiber, targetoid fiber, and rods), the tetanized PL produced numerous SCBs with a predictable time course. They were induced in both type 1 and 2 fibers of PL, which is composed predominantly (95%) of type 2 fibers, in contrast to SOL (85% type 1 fibers). Factors inducing SCBs may include immobilization, shortening, intact innervation, and disuse atrophy.


Resolution of glpA and glpT loci into separate operons in Escherichia coli K-12 strains.
The independent insertion of bacteriophage Mu into the gene coding for anaerobic sn-glycerol 3-phosphate dehydrogenase (glpA) or into the genes coding for sn-glycerol 3-phosphate transport (glpT) suggested that these two closely linked loci are in separate operons.


Secondhand smoke policies at state and county fairs.
We sought to assess the smoking policies at state and county fairs in North Carolina. We contacted North Carolina fair managers by telephone to solicit participation in a survey that assessed the extent to which fairs have written policies about smoking and secondhand smoke (SHS) exposure, managers' beliefs concerning the health risks associated with SHS exposure, and specific reasons that might prompt managers to adopt smoke-free policies. Attempts were made to contact 47 fair managers, and 37 (66.0%) participated in the study. We found that although almost two-thirds of fairs prohibited smoking indoors, the vast majority (83.9%) had no limits on outdoor smoking. Most fair managers (84.6%) acknowledged that SHS may cause lung cancer, and a majority (51.6%) reported a belief that their patrons would largely be supportive of a more restrictive policy. Fair managers' responses were primarily based on their own opinions, estimates, and attitudes. Because of the high number and density of fair patrons, unrestricted outdoor smoking likely exposes most patrons to SHS. Action to eliminate all exposure to SHS at state and county fairs is needed.


Crystallization and preliminary X-ray investigation of factor D of human complement.
Human factor D, an essential enzyme of the alternative pathway of complement activation, has been crystallized. Crystals were grown by vapor diffusion using polyethylene glycol 6000 and NaCl as precipitants. The factor D crystals are triclinic and the space group is P1 with unit cell dimensions a = 40.8 A, b = 64.7 A, c = 40.3 A, alpha = 101.0 degrees, beta = 109.7 degrees, gamma = 74.3 degrees. The unit cell contains two molecules of factor D related by a non-crystallographic 2-fold axis. The crystals grow to dimensions of 0.8 mm x 0.5 mm x 0.2 mm within five days, are stable in the X-ray beam and diffract beyond 2.5 A.


Intracerebral fibroma: light and electron microscopic study.
The light and electron microscopic findings of a surgically excised intracerebral mass is presented. The ultrastructural study led to definitely exclude both meningioma (that was the original diagnosis at surgery) and intracerebral schwannoma, while substantiating the uncommon final diagnosis of fibroma. The true intracerebral fibroma has exceptionally been described in the past. The seven so far reported cases are shortly reviewed.


Experimental Investigation of Supercritical CO2-Rock-Water Interactions in a Tight Formation with the Pore Scale during CO2-EOR and Sequestration.
In recent years, gas injection, especially CO2 injection, has been acknowledged as a promising approach for enhanced oil recovery (EOR) and CO2 capture and storage (CCS), especially for tight reservoirs. However, when CO2 is injected into the oil reservoirs, it can disturb the equilibrium of the system and lead to chemical reactions between CO2, formation water, and reservoir rocks. The reactions will alter some geochemical and physicochemical characteristics of the target reservoirs. However, the reactions still lack quantitative characterization at the pore scale, especially under reservoir conditions. Herein, we conducted an experimental study of the interactions between CO2, brine, and rocks in the Mahu oilfield at 20 MPa and 70 °C. The low-field nuclear magnetic resonance (LF-NMR) measurements showed that the incremental amplitude for tight cores of CO2-rock-water tests was larger than that for CO2-rock tests, and the amplitude alteration presented significant differences corresponding to different types of minerals and pores. Furthermore, the interplanar spacing of the core samples was increased with the increase of reaction time in the CO2-rock experiments but still lower than that in CO2-rock-water tests. This research demonstrated evident changes in the geochemistry in tight reservoirs caused by CO2, brine, and rock reactions. The results of this study may provide a significant reference for the exploration of similar reservoirs in the field of CO2-EOR and CO2 sequestration.


[Pacemaker and implantable defibrillators with telemedical support].
Recent developments in pacemaker and ICD therapy can be characterized by a rising number of implantations (especially in the field of ICD and CRT systems) and an increasing complexity of the units involved. Problems evolving from this trend are the soaring numbers of necessary follow-up examinations, issues of patient safety and the necessity of device management by specialized physicians. Telemonitoring offers various possibilities of improvement in these areas. The manufacturers of the devices have developed applicable solutions for concepts of care including telemedical monitoring of patients with pacemakers, ICD and CRT systems. The systems commonly include an implant capable of either automatic or manual data transmission, a device for transmitting the implant's data (mobile communication or fixed line network), a server managing the information and a front-end (internet-based) platform for the physician. Multiple clinical trials have verified the stability and the security of this method of data transmission. Telemedical monitoring can be used in order to improve the monitoring of the patients' state of health (e. g., patients with CRT systems because of their CHF) and the management of arrhythmias (e. g., patients suffering from paroxysmal atrial fibrillation). Telemonitoring allows the intervals between follow-up check-ups to be individualized, thus, leading to financial savings. The telemedical monitoring of patients with ICD and CRT systems facilitates new opportunities for networked follow-up care and comprehensive medical treatment.


Emission and its back-reaction accompanying electron motion in relativistically strong and QED-strong pulsed laser fields.
The emission from an electron in the field of a relativistically strong laser pulse is analyzed. At pulse intensities of J>or=2x10(22) W/cm(2) the emission from counterpropagating electrons is modified by the effects of quantum electrodynamics (QED), as long as the electron energy is sufficiently high: E>or=1 GeV . The radiation force experienced by an electron is for the first time derived from the QED principles and its applicability range is extended toward the QED-strong fields.


Effects of the 5-HT(7) receptor antagonist SB-269970 microinjected into the dorsal raphe nucleus on REM sleep in the rat.
The effects of SB-269970, a selective 5-HT(7) receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. SB-269970 was infused directly into the dorsal raphe nucleus (DRN) during the light phase. The 5-HT(7) receptor antagonist (0.25-1.0 mM) induced a significant reduction of REM sleep and of the number of REM periods whereas REM sleep latency was augmented. Pretreatment with the GABA(A) receptor agonist muscimol (1.0-2.0 mM), which by itself did not affect sleep variables, prevented the decrease of REM sleep induced by SB-269970 (1.0 mM). Our results indicate that the 5-HT(7) receptor is involved in the effect of DRN serotonergic (5-HT) neurons on brainstem structures that act to promote and induce REM sleep. We propose that the SB-269970-induced suppression of REM sleep is dependent upon the inhibition of GABA release in the DRN.


Lichen planus of the esophagus: what dermatologists need to know.
Esophageal lichen planus (ELP) is a rare manifestation of mucocutaneous lichen planus (LP). We aimed to report our experience and review all cases of ELP reported in the English-language literature. We report our experience with 4 cases and reviewed PubMed for reports of ELP. Cases were evaluated for age of onset, sex, location of LP, relationship of the onset of ELP to extra-ELP, endoscopic findings, whether biopsy was performed, histopathology of esophageal biopsy specimens, medical history (including gastrointestinal history), development of esophageal squamous cell carcinoma, therapies tried, and response to treatment. A total of 72 cases of ELP were studied. In all, 87% of patients were female, with a median age of 61.9 years at time of diagnosis. Dysphagia was present in 81% and odynophagia was present in 24%. Oral LP was present in 89%, anogenital/vulvar LP in 42%, and cutaneous LP in 38%. Fourteen patients developed ELP as the sole or first manifestation of LP. Proximal esophageal lesions were present in 64%, distal in 11%, and both proximal and distal in 26%. Histology was "consistent with" LP in 71%. Four patients developed squamous cell carcinoma in association with ELP. This is a review of our cases and others reported in the literature. ELP is underrecognized and underreported. There is often a significant delay between the onset of symptoms and the diagnosis. Malignant transformation of ELP to squamous cell carcinoma has been reported.


Electrochemical analysis of endosulfan using a C18-modified carbon-paste electrode.
Successful applications of different analytical procedures to determine quantitatively endosulfan and its metabolites in aqueous media can be found in recent literature. Fundamentally, they have made use of solid-phase extraction (SPE) and gas (GC) or liquid chromatography (LC), sometimes coupled to mass spectrometry (MS). In this paper, a new and alternative methodology to determine quantitatively endosulfan in aqueous media is reported. A C18-modified carbon-paste electrode has been used to determine voltammetrically endosulfan, despite its unfavourable electrochemical properties and behaviour. The methodology proposed is based on the decrease experienced by the peak intensity corresponding to voltammetric signals of Cu(II) when successive and constant additions of endosulfan are carried out. This decrease is directly proportional to the concentration of endosulfan what allows to perform an indirect quantification of the pesticide. The detection limit obtained is 40 ng l(-1), this value being under the limits specified by European norms and EPA reports.


Proteome changes in platelets activated by arachidonic acid, collagen, and thrombin.
Platelets are small anucleated blood particles that play a key role in the control of bleeding. Platelets need to be activated to perform their functions and participate in hemostasis. The process of activation is accompanied by vast protein reorganization and posttranslational modifications. The goal of this study was to identify changes in proteins in platelets activated by different agonists. Platelets were activated by three different agonists - arachidonic acid, collagen, and thrombin. 2D SDS-PAGE (pI 4-7) was used to separate platelet proteins. Proteomes of activated and resting platelets were compared with each other by Progenesis SameSpots statistical software; and proteins were identified by nanoLC-MS/MS. 190 spots were found to be significantly different. Of these, 180 spots were successfully identified and correspond to 144 different proteins. Five proteins were found that had not previously been identified in platelets: protein CDV3 homolog, protein ETHE1, protein LZIC, FGFR1 oncogene partner 2, and guanine nucleotide-binding protein subunit beta-5. Using spot expression profile analysis, we found two proteins (WD repeat-containing protein 1 and mitochondrial glycerol-3-phosphate dehydrogenase) that may be part of thrombin specific activation or signal transduction pathway(s). Our results, characterizing the differences within proteins in both activated (by various agonists) and resting platelets, can thus contribute to the basic knowledge of platelets and to the understanding of the function and development of new antiplatelet drugs.


Histamine in brain may have no role for histaminergic control of food-related drinking in the rat.
Adult male Sprague-Dawley rats surgically fitted with a cannula positioned in the third cerebral ventricle were tested for drinking after exogenous histamine or after eating with or without antagonism of H1 and/or H2 receptors for histamine using intracerebroventricular (ICV) dexbrompheniramine (DXB; 12.5-50 micrograms) or cimetidine (C; 25-100 micrograms). Histamine (0.06-16 micrograms) given ICV failed to elicit drinking. For rats drinking in response to subcutaneous (SC) histamine, ICV DXB alone did not affect drinking, whereas ICV DXB plus C, and ICV C given alone inhibited drinking. Such inhibition appeared to be relatively selective for drinking elicited by SC histamine, because ICV 50 micrograms DXB plus 100 micrograms C abolished drinking elicited by SC histamine, but failed to inhibit drinking after 12-hr water deprivation. When rats ate and drank after food deprivation, ICV DXB alone and ICV DXB plus C did not significantly inhibit food-related water intake. The inhibition of food-related drinking by ICV 100 micrograms C given alone was accompanied by inhibition of eating. In summary, histamine had unimpressive dipsogenic effects when given ICV, ICV DXB and C inhibited drinking elicited by SC histamine, but ICV DXB and C failed to inhibit food-related drinking in a manner parallel to the selective effects of intraperitoneal injection of these drugs on drinking elicited by eating. This suggests that it is histamine and histamine receptors in the periphery rather than in brain that have the predominant role for a histaminergic mechanism for drinking elicited by eating in the rat, but our findings do not rule out a role(s) for histamine in brain in the control of ingestive behavior.


Autophagy in adipogenesis: Molecular mechanisms and regulation by bioactive compounds.
White adipose tissue expands rapidly due to increased adipocyte number (hyperplasia) and size (hypertrophy), which results in obesity. Adipogenesis is a process of the formation of mature adipocytes from precursor cells. Additionally, obesity-related metabolic complications, such as fatty liver and insulin resistance, are linked to adipogenesis. On the contrary, autophagy is a catabolic process; essential to maintain cellular homeostasis via the degradation or recycling of unnecessary or damaged components. Importantly, autophagy dictates obesity and adipogenesis. Hence, a clear understanding of how autophagy regulates adipogenesis is crucial for drug development and the prevention and treatment of obesity and its associated disorders, such as type 2 diabetes, cardiovascular disease, and cancer. In this review, we highlighted recent findings regarding the crosstalk between adipogenesis and autophagy, as well as the molecules involved. Furthermore, the review discussed how bioactive compounds regulate adipogenesis by manipulating autophagy and underlying molecular mechanisms. Based on in vitro and animal studies, we summarized the effects of bioactive compounds on adipogenesis and autophagy. Hence, human studies are necessary to validate the effectiveness and optimal dosage of these bioactive compounds.


The Endangered State of Medicare Reimbursement for Cardiothoracic Surgery: A Call to Action.
Reimbursement for cardiothoracic surgery continues to be threatened with enormous financial cuts ranging from 5% to 10% in recent years. In this policy perspective, we describe the history of reimbursement for cardiothoracic surgery, highlight areas in need of urgent reform, propose possible solutions that Congress and the Executive Branch may enact, and call cardiothoracic surgeons to action on this critical issue. Meaningful engagement of members of The Society of Thoracic Surgeons with their elected representatives is the only way to prevent these cuts.


Brain MRI findings in COVID-19 patients with PRES: A systematic review.
Numerous case reports and case series have described brain Magnetic Resonance Imaging (MRI) findings in Coronavirus disease 2019 (COVID-19) patients with concurrent posterior reversible encephalopathy syndrome (PRES). We aim to compile and analyze brain MRI findings in patients with COVID-19 disease and PRES. PubMed and Embase were searched on April 5th, 2021 using the terms "COVID-19", "PRES", "SARS-CoV-2" for peer-reviewed publications describing brain MRI findings in patients 21 years of age or older with evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and PRES. Twenty manuscripts were included in the analysis, which included descriptions of 30 patients. The average age was 57 years old. Twenty-four patients (80%) required mechanical ventilation. On brain MRI examinations, 15 (50%) and 7 (23%) of patients exhibited superimposed foci of hemorrhage and restricted diffusion respectively. PRES is a potential neurological complication of COVID-19 related disease. COVID-19 patients with PRES may exhibit similar to mildly greater rates of superimposed hemorrhage compared to non-COVID-19 PRES patients.


Nucleotide and deduced amino acid sequence of human ribosomal protein L18.
Ribosomal protein L18 mRNA is overexpressed in human colorectal cancer compared to normal colon tissue. We report the nucleotide sequence of human L18 cDNA derived from a normal colon source. There were no mutational changes in segments of L18 cDNA derived from two tumor sources. The L18 cDNA was 690 base pairs long and predicts a single open reading frame of 564 nucleotides, encoding 188 amino acids with a M(r) = 21,621, it is homologous to rat L18 and Xenopus laevis L14.


Synergetic loss of heavy metal and phosphorus: Evidence from geochemical fraction and estuary sedimentation.
The synergetic loss mechanism of heavy metals (HMs) and phosphorus (P), as well as the relationships between their different geochemical fractions remain unclear. This study employs field research, source identification and sedimentary geochemistry in Yellow River basin to investigate the internal mechanisms of the different geochemical fractions, terrestrial source signatures, and synergetic loss fluxes. The average contents of As, Cd, Cr, Cu, Pb, Zn and P in the basin were 8.29 mg/kg, 0.15 mg/kg, 47.52 mg/kg, 11.78 mg/kg, 10.65 mg/kg, 46.56 mg/kg and 578.78 mg/kg, respectively. Based on Pearson's correlation and redundancy analyses, the impact factors on the transport of HMs and P, and the internal relationships between different geochemical fractions were analyzed. According to the constant rate of supply (CRS) model, the terrestrial losses of As, Cd, Cr and Cu showed significant positive relationships with the TP flux, with r2 value of 0.981, 0.991, 0.996 and for 0.984, respectively. It has been proven that the extensive fine particles in the Yellow River basin carry a large amount of diffuse pollutants, thus ultimately increasing the estuarine pollutant load. This research provides new insights from the level of microscopic fractions to macroscopic fluxes to investigate the impacts of anthropogenic activity on regional environmental changes.


Chronic exertional compartment syndrome in adductor pollicis muscle: case report.
We report a case of chronic exertional compartment syndrome in the adductor pollicis that was confirmed by measuring elevated compartment pressure. Specific finding of magnetic resonance imaging, increased T2 signal intensity in the involved compartment, was also useful for the diagnosis. Pain was relieved by fasciotomy through a volar approach.


Borneol in cardio-cerebrovascular diseases: Pharmacological actions, mechanisms, and therapeutics.
With the coming acceleration of global population aging, the incidence rate of cardio-cerebrovascular diseases (CVDs) is increasing. It has become the leading cause of human mortality. As a natural drug, borneol (BO) not only has anti-inflammatory, anti-oxidant, anti-apoptotic, anti-coagulant activities and improves energy metabolism but can also promote drugs to enter the target organs or tissues through various physiological barriers, such as the blood-brain barrier (BBB), mucous membrane, skin. Thus, it has a significant therapeutic effect on various CVDs, which has been confirmed in a large number of studies. However, the pharmacological actions and mechanisms of BO on CVDs have not been fully investigated. Hence, this review summarizes the pharmacological actions and possible mechanisms of BO, which provides novel ideas for the treatment of CVDs.


Lithium carbonate response in depression. Prediction by unipolar/bipolar illness, average-evoked response, catechol-O-methyl transferase, and family history.
The antidepressant efficacy of lithium carbonate was assessed in a double-blind trial in 23 hospitalized depressed patients. Unequivocal response was significantly more frequent in bipolar than in unipolar depressed patients. Lithium carbonate responders had a greater visual average-evoked response amplitude increase in response to increased stimulus intensity, termed "augmenting". No correlation could be demonstrated between lithium carbonate efficacy and either erythrocyte catechol-O-methyl transferase activity, age of symptom onset, number of hospitalizations, or family history of affective disorders.


Two Plasmodium falciparum merozoite proteins binding to erythrocyte band 3 form a direct complex.
Erythrocyte invasion by malaria parasites requires multiple protein interactions. Our earlier studies showed that erythrocyte band 3 is an invasion receptor binding Plasmodium falciparum merozoite surface protein 1 and 9 (MSP1, MSP9) existing as a co-ligand complex. In this study, we have used biochemical approaches to identify the binding sites within MSP1 and MSP9 involved in the co-ligand complex formation. A major MSP9-binding site is located within the 19kDa C-terminal domain of MSP1 (MSP1(19)). Two specific regions of MSP9 defined as Delta1a and Delta2 interacted with native MSP1(19). The 42 kDa domain of MSP1 (MSP1(42)) bearing MSP1(19) in the C-terminus bound directly to both MSP9/Delta1a and Delta2. Thus, the regions of MSP1 and MSP9 interacting with the erythrocyte band 3 receptor are also responsible for assembling the co-ligand complex. Our evidence suggests a ternary complex is formed between MSP1, MSP9, and band 3 during erythrocyte invasion by P. falciparum.


A study on the development of a filing system for funduscopic images with a personal computer for Twin AMHTS.
A filing system for ocular funduscopic image data was developed by using a personal computer for the Twin AMHTS. The development of the system was tried as one of the data transfer system including image data between two similar AMHTSs named the Twin AMHTS through the information network system. The filing system is capable of storing 26782 data of ophthalmoscopic pictures with a data compression mode by using a magneto-optical disk (MOD) whose storage capacity of both sides is 616 MB. It takes no long time for retrieval and display of the image data in the filing system. Good quality of compression and decompression obtained and reproducibility of the ocular fundus picture is favorable regardless of normal or abnormal cases. As a result, it is suggested that the developed system has practical utility although it requires more improvement.


Prevalence of Third-party Tracking on Medical Journal Websites.
This cross-sectional study investigates web tracking prevalence and characteristics on medical journal websites.


Predictive value of serum carbohydrate antigen 19-9 in malignant intraductal papillary mucinous neoplasms.
The goal of the present study was to evaluate the predictive value of serum carbohydrate antigen 19-9 (CA 19-9) in the diagnosis of malignant intraductal papillary mucinous neoplasms of pancreas (IPMNs). Eighty-six patients with pathological diagnosis of IPMNs in Zhongshan Hospital between March 1999 and November 2008 were retrospectively reviewed. Data reflecting clinical characteristics, tumor marker level, and prognosis were collected. The potential predictive value of CA 19-9 was analyzed by receiver operating characteristic (ROC) curve. Eighty-six consecutive patients with IPMNs all underwent surgical intervention. A high level of CA 19-9 or carcinoembryonic antigen (CEA) was associated with more advanced stage of malignant IPMNs. Carbohydrate antigen 19-9 was significant for judging malignant IPMNs in the binary logistic regression model (p=0.047). The hazard ratio was 1.014, whose 95.0% confidence interval was 0.91-1.028. Receiver operating characteristic analysis showed that the serum CA 19-9 level had good predictive value for malignant or invasive IPMNs, postoperative survival, and disease-specific recurrence. The area under the curve (AUC) was 0.856, 0.893, 0.815, and 0.857 (p<0.05), respectively. According to the follow-up, mean survival time for groups with CA 19-9>63.60 U/ml was dramatically shorter than that for groups with CA 19-9≤63.60 U/ml (57.38±2.85 versus 29.24±5.82 [months]; p<0.01). Serum CA 19-9 level has good predictive value for malignant or invasive IPMNs. Patients with CA 19-9 > 63.60 U/ml had poor postoperative prognosis in IPMNs. Preoperative abnormal serum CA 19-9 might be predictive for an aggressive surgical intervention in IPMNs.


Influence of the hip on patients with patellofemoral pain syndrome: a systematic review.
Patellofemoral pain syndrome (PFPS) is one of the most common conditions limiting athletes. There is a growing body of evidence suggesting that dysfunction at the hip may be a contributing factor in PFPS. MEDLINE (1950-September 2010), CINAHL (1982-September 2010), and SPORTDiscus (1830-September 2010) were searched to identify relevant research to this report. Studies were included assessing hip strength, lower extremity kinematics, or both in relation to PFPS were included. Studies included randomized controlled trials, quasi-experimental designs, prospective epidemiology, case-control epidemiology, and cross-sectional descriptive epidemiology in a scientific peer-reviewed journal. PFPS is associated with decreased hip strength, specifically at the abductors and external rotators. There is a correlation between PFPS and faulty hip mechanics (adduction and internal rotation). There is a link between the strength and position of the hip and PFPS. These patients have a common deficit once symptomatic. Hip strengthening and a coordination program may be useful in a conservative treatment plan for PFPS.


Permeability of the bladder mucosa to thiotepa, adriamycin, and daunomycin in men and rabbits.
The permeability of the bladder mucosa to thiotepa and to the anthraquinonic antibiotics, adriamycin and daunomycin, was investigated both in humans and in experimental animals. Instillations in rabbits were performed either in intact males or in animals with ligated ureters. Absorption of thiotepa was significantly higher than that of the antibiotics both in men and in rabbits. Furthermore, a qualitative difference was observed in rabbits in relation to time and with regard to fixation to vesical tissues. In man, absorption was highest after transurethral surgery. It was also increased in cases with extensive anaplastic tumours or in the presence of acute inflammatory reactions.


The Influence of Unemployment and Disability Status on Clinical Outcomes in Patients Receiving Surgery for Low Back-Related Disorders: An Observational Study.
Employment status plays an essential role as a social determinant of health. Unemployed are more likely to have a longer length of hospital stay and a nearly twofold greater rate of 30 day readmission than those who were well employed at the time of back surgery. This study aimed to investigate whether employment status influenced post-surgery outcomes and if so, the differences were clinically meaningful among groups. This retrospective observational study used data from the Quality Outcomes Database Lumbar Registry. Data refinement was used to isolate individuals 18 to 64 who received primary spine surgeries and had a designation of employed, unemployed, or disabled. Outcomes included 12 and 24 month back and leg pain, disability, patient satisfaction, and quality of life. Differences in descriptive variables, comorbidities, and outcomes measures (at 12 and 24 months) were analyzed using chi-square and linear mixed-effects modeling. When differences were present among groups, we evaluated whether they were clinically significant or not. Differences (between employed, unemployed, and disabled) among baseline characteristics and comorbidities were present in nearly every category (p<0.01). In all cases, those who were disabled represented the least healthy, followed by unemployed, and then employed. Clinically meaningful differences for all outcomes were present at 12 and 24 months (p<0.01). In post hoc analyses, differences between each group at nearly all periods were found. The findings support that the health-related characteristics are markedly different among employment status groups. Group designation strongly differentiated outcomes. These findings suggest that disability and unemployment should be considered when determining prognosis of the individual.


Anergy and suppression in B-cell responses.
Two main ideas have been put forward to explain the unexpectedly low anti-hapten antibody titres which can result from pre-priming a mouse with carrier before hapten-carrier immunization. The first involves the interaction of a network of idiotype-specific suppressor T cells, the second instead arguing for the role of intrinsic B-cell anergy. This paper proposes that the data available can equally be interpreted as reflecting the suboptimal interaction between T and B cells at differing stages of maturity, provided that memory B cells can be divided into two subsets. Further, it is suggested that these considerations must be taken into account in the analysis of B-cell anergy in receptor transgenic mice.


Percutaneous cystostomy in paraplegia--a follow-up of 41 patients.
Percutaneous cystostomy using a fine calibre (9 Charriere) plastic trocar and cannula has been used in 51 male patients in the early weeks following spinal cord injury. The results are satisfactory. Of the last ten patients none has been catheterised per urethram; eight of these patients are now passing urine satisfactorily using a condom urinal.


Papillary muscle resection as a treatment for midventricular obstruction.
We have experienced a surgically treated case of midventricular obstruction. A simple mitral valve replacement was effective to relieve the obstruction and to increase the cavity of the left ventricular outflow tract without a myectomy through the aortic valve.


Putting the heat on sex determination.
Sex determination and differentiation are inherently fascinating to both layperson and geneticist. Major advances have accelerated interest in the molecular genetic events mediating these processes in nematodes, flies, mice and humans. Far less attention has been paid to those organisms, particularly reptiles, where sex is determined by environmental cues. However, recent experimental evidence suggests that the two modes of sex determination may not only share common genetic elements, but may also be regulated by similar mechanisms. We argue that the ability to manipulate sex by temperature provides a particularly suitable model for exploring the molecular basis of this fundamental biological process.


Synaptic excitation and inhibition resulting from direct action of acetylcholine on two types of chemoreceptors on individual amphibian parasympathetic neurones.
1. Synaptic transmission was studied in visually identified parasympathetic ganglion cells that modulate the heart beat of the mudpuppy Necturus maculosus).2. The brief pulse of acetylcholine (ACh) released from terminals of the vagus nerve after each impulse can produce two distinct post-synaptic responses in individual principal cells of the ganglion: (i) within a milli-second of release, ACh generates a rapid and strong excitatory post-synaptic potential (e.p.s.p.) that normally initiates a post-synaptic impulse; (ii) this excitation is usually followed by a slow hyperpolarizing inhibitory post-synaptic potential (i.p.s.p.) that lasts for several seconds. The magnitude and time course of the i.p.s.p. depends on the frequency and number of vagal stimuli. When the hydrolysis of ACh is inhibited by prostigmine, a train of nerve stimuli may be followed by an i.p.s.p. lasting half a minute or longer.3. The rapid e.p.s.p. and slow i.p.s.p. result from the direct action of ACh on two different types of chemoreceptors in the post-synaptic membrane of the principal cell. The e.p.s.p. can be preferentially blocked by the nicotinic antagonist dihydro-beta-erythroidine (5 x 10(-7)M), while the i.p.s.p. is selectively blocked by the muscarinic antagonist atropine (5 x 10(-9)M).4. Potentials resembling nerve-evoked e.p.s.p.s and i.p.s.p.s can be produced by iontophoretic release of ACh from micropipettes onto the post-synaptic membrane. Application of the muscarinic agonist bethanechol generates exclusively inhibitory responses.5. The reversal potential for the i.p.s.p. is about -105 mV, which is approximately the equilibrium potential for potassium (E(K)). When the external K(+) concentration is altered, the reversal potential for inhibition is shifted to the new value of E(K) as expected from the Nernst equation. Changes in the external Na(+) and Cl(-) concentrations have no appreciable effect on the reversal potential. Thus, the i.p.s.p. is the result of a conductance increase for K(+).6. The conductance change producing the i.p.s.p. is voltage sensitive. When the membrane potential is shifted from -40 to -60 mV, the i.p.s.p becomes larger and longer. Beyond -60 mV the inhibitory response decreases in proportion to the driving force on K(+) without any further change in time course.7. The inhibitory response produced by an iontophoretically applied pulse of bethanechol has a delayed onset of about 150 msec at 24 degrees C. The early portion of this response, including the delay, is proportional to t(3), where t is time. The proportionality factor (the apparent rate constant) decreases elevenfold when the temperature is lowered by 10 degrees C. This suggests that a multi-step process is involved in the activation of the conductance increase that leads to the inhibitory response. Inhibitory responses with similar kinetics were produced in heart muscles of the mudpuppy upon application of ACh.


Mycotic aneurysm of the carotid artery. A case report and review of the literature.
A patient with a mycotic aneurysm of the common carotid artery caused by septic cervical lymph node disease is discussed. In view of the preexistent occlusion of the internal and external carotid artery, a ligation of the carotid artery was performed.


Influence of anisotropy on peri-implant stress and strain in complete mandible model from CT.
This paper reveals the influence of elastic anisotropy for the peri-implant stress and strain in personalized mandible. First, from CT data, the individual geometry of the complete range of mandible was well reproduced, also the separation between cortical and cancellous bone. Then, by an ad hoc automatic mesh generator integrated with anisotropic material assignment function, high quality anisotropic finite element model of the complete mandible was created, with two standard threaded implants embedded in posterior zone. The values of principal stress and strain in surrounding bone were evaluated under buccolingual oblique loading, and compared to that of the same FE model with equivalent isotropic material. Results of the analyses demonstrated that the percentage increase of stress and strain in anisotropic case reached up to 70%. It is concluded that anisotropy has significant effects on peri-implant stress and strain and careful consideration should be given to its use in biomechanical FE studies.


Effect of selenium supplementation on HIV-1 RNA detection in breast milk of Tanzanian women.
Selenium supplementation for women infected with HIV may increase genital shedding of HIV-1, however, to our knowledge, no studies have examined the effect on viral shedding in breast milk. The aim of this study was to determine the effect of selenium supplementation on HIV-1 RNA detection in breast milk of HIV-infected women. HIV-infected pregnant women enrolled at 12 to 27 wk gestation in a randomized, double-blind, placebo-controlled trial of daily selenium (200 μg as selenomethionine) had cell-free HIV-1 RNA quantified in breast milk at 4 to 9 wk postpartum. All participants received high-dose multivitamins containing vitamin B complex, C, and E as standard of care. The proportion of women with detectable (>50 copies/mL) HIV-1 RNA in breast milk appeared to be increased in the selenium group (36.4%) compared with those in the placebo group (27.5%) among the total cohort (N = 420), but results were borderline statistically significant (relative risk [RR], 1.32; 95% confidence interval [CI], 1.00-1.76; P = 0.05). In secondary analyses, the proportion of women with detectable HIV-1 RNA in breast milk was significantly greater in the selenium group (37.8%) compared with placebo group (27.5%) among women who did not receive highly active antiretroviral therapy (HAART; RR, 1.37; 95% CI, 1.03-1.82; P = 0.03). This relationship was primarily due to a significant effect of selenium among primiparous women (RR, 2.24; 95% CI, 1.30-3.86; P < 0.01), but not multiparous women (RR, 1.14; 95% CI, 0.81-1.59; P = 0.54) (P-value for interaction = 0.02). Too few women received HAART in this study (n = 12) to establish the effect of selenium supplementation. Selenium supplementation appears to increase HIV-1 RNA detection in breast milk among primiparous women not receiving HAART. Safety studies among pregnant women on HAART need to be conducted before administering selenium-containing supplements.


Cardiac Toxicity: Using Angiotensin-Converting Enzyme Inhibitors to Prevent Anthracycline-Induced Left Ventricular Dysfunction and Cardiomyopathy.
Anthracycline chemotherapies are effective in many different types of cancer. However, cumulative doses are associated with irreversible cardiac toxicity, most frequently manifested in the development of left ventricular dysfunction, cardiomyopathy, and congestive heart failure. The onset of cardiomyopathy and subsequent heart failure can result in the interruption or discontinuation of therapy. Cardioprotective agents, particularly angiotensin- converting enzyme inhibitors, have been shown to slow the progression of left ventricular dysfunction and prevent heart failure. This review assesses the efficacy of angiotensin-converting enzyme inhibitors in the prevention of anthracycline-induced left ventricular dysfunction. A literature search was performed using four electronic databases. Evidence from this review suggests that angiotensin-converting enzyme inhibitors may be effective in preventing or reducing anthracycline- induced left ventricular dysfunction and subsequent cardiomyopathy and heart failure.


The feasibility of a pragmatic randomised controlled trial to compare usual care with usual care plus individualised homeopathy, in children requiring secondary care for asthma.
To test the feasibility of a pragmatic trial design with economic evaluation and nested qualitative study, comparing usual care (UC) with UC plus individualised homeopathy, in children requiring secondary care for asthma. This included recruitment and retention, acceptability of outcome measures patients' and health professionals' views and experiences and a power calculation for a definitive trial. In a pragmatic parallel group randomised controlled trial (RCT) design, children on step 2 or above of the British Thoracic Society Asthma Guidelines (BTG) were randomly allocated to UC or UC plus a five visit package of homeopathic care (HC). Outcome measures included the Juniper Asthma Control Questionnaire, Quality of Life Questionnaire and a resource use questionnaire. Qualitative interviews were used to gain families' and health professionals' views and experiences. 226 children were identified from hospital clinics and related patient databases. 67 showed an interest in participating, 39 children were randomised, 18 to HC and 21 to UC. Evidence in favour of adjunctive homeopathic treatment was lacking. Economic evaluation suggests that the cost of additional consultations was not offset by the reduced cost of homeopathic remedies and the lower use of primary care by children in the homeopathic group. Qualitative data gave insights into the differing perspectives of families and health care professionals within the research process. A future study using this design is not feasible, further investigation of a potential role for homeopathy in asthma management might be better conducted in primary care with children with less severe asthma.