Veno-arterial CO2 difference and respiratory quotient after cardiac arrest: An observational cohort study.
To characterize venous-arterial CO2 difference (ΔpCO2) and the respiratory quotient (RQ) in post cardiac arrest patients and evaluate the association between these parameters and patient outcome. Data were obtained retrospectively from post cardiac arrest patients admitted between 2007 and 2016 to a medical intensive care unit. Comatose, adult patients in whom arterial and venous blood gas analyses were concomitantly performed in the first 24 h were included. Patients were grouped according to the time-point of sampling; 0-6, 6-12 and 12-24 h after admission. 308 patients were included; 174 (56%) died before ICU discharge and 212 (69%) had an unfavorable neurologic outcome. RQ was associated with ICU mortality (OR:1.09 (95%CI: 1.04-1.14; p < 0.01)), although not with neurological outcome. ΔpCO2 was negatively associated with both ICU mortality (OR: 0.92 (95%CI: 0.86-0.99; p = 0.02)) and poor neurologic outcome (adjusted OR: 0.93 (95%CI: 0.87-0.99; p = 0.02)). ΔpCO2 predicted an elevated RQ; a ΔpCO2 above 8.5 mmHg identified a high RQ with reasonable sensitivity and specificity. RQ was associated with ICU mortality and ΔpCO2 identified elevated RQ in the early phase after cardiac arrest. However, ΔpCO2 were negatively associated with both ICU mortality and neurologic outcome.


Shotgun metagenomics of dust microbiome from flight deck and cabin in civil aviation aircraft.
Microbial exposure is related to the health of passengers on commercial aircraft, but no studies characterized the microbial composition at the species level and identified their ecological determinants. We collected vacuum dust from floor and seat surfaces in flight decks and cabins of 18 aircraft, and amplification-free shotgun metagenomics was conducted to characterize the microbial composition. In total, 7437 microbial taxa were identified. The relative abundance for bacteria, eukaryote, viruses, and archaea was 96.9%, 1.8%, 0.3%, and 0.03%, respectively. The top bacterial species mainly derived from outdoor air and human skin included Sphingomonas, Corynebacterium, Micrococcus luteus, Variovorax paradoxus, Paracoccus dentrificans, and Propionibacterium acnes. The abundance of NIAID-defined pathogens was low, accounted for only 0.23% of total microbes. The microbial species and functional composition were structured by the indoor surface type (R2 = 0.38, Adonis), followed by the manufacturer of the aircraft (R2 = 0.12) and flight duration (R2 = 0.07). Indoor surfaces affected species derived from different habitats; the abundance of dry skin and desiccated species was higher on textile surfaces, whereas the abundance of moist and oily skin species was higher on leather surfaces. The growth rates for most microbes were stopped and almost stopped.


Paroxetine in the treatment of dysthymic disorder without co-morbidities: A double-blind, placebo-controlled, flexible-dose study.
Few published studies have evaluated selective serotonin reuptake inhibitors in dysthymia without current co-morbid major depression. In this 12-week study, 40 dysthymic patients were randomly assigned to either placebo (n=19) or 20-40 mg/day of paroxetine (n=21). At endpoint, the paroxetine group showed significantly greater improvement on the Clinical Global Impression Scale, Beck Depression Inventory, and Quality of Life Enjoyment and Satisfaction Questionnaire (p<0.05), and a trend to superiority over placebo on the Hamilton Depression Rating Scale. Response and remission were significantly higher with paroxetine than placebo (p<0.05). There were no significant differences in drop out rates or frequency of adverse effects, except for excessive sweating (greater with paroxetine, p=0.04). Reporting of multiple side effects was also higher with paroxetine than with placebo (p=0.02). Paroxetine is more effective than placebo in improving symptoms and quality of life in dysthymia, and is generally tolerable.


Mobile alcohol biosensors and pharmacotherapy development research.
Recent advances in biosensor technology herald a major shift in the way alcohol use will be tracked in humans. Wearable biosensors can passively and continuously monitor wearers' alcohol consumption in real time. An important application of these biosensors is to improve the way medication for alcohol use disorder (AUD) is tested in clinical research. Both laboratory-based screening paradigms and clinical trials have methodological problems that impact their efficiency and predictive validity. Medication screening using laboratory-based methods is a resource-intensive assessment of a single episode of behavior in a non-representative setting. Clinical trials rely on participant self-report to document medication-induced changes in drinking behavior. This review describes how mobile biosensors can be leveraged to improve AUD medication development research. We first review the current state of alcohol biosensor technology with a focus on strengths and limitations of the devices. We describe how multiple biosensors can be combined to create a far more detailed record of drinking compared to single biosensor platforms. We then discuss each phase of the medication development pipeline in turn (i.e., phases 1-4) and describe how mobile biosensors can be incorporated in standard medication testing paradigms to improve efficiency and predictive validity. We conclude with discussion of challenges associated with using currently available biosensors for medication testing and recommendations for researchers wishing to incorporate alcohol biosensors into their own research.


Lactation Induction in a Transgender Woman: Macronutrient Analysis and Patient Perspectives.
Induction of lactation in a non-gestational parent has numerous potential benefits including parent-child bonding, optimal nutrition, and health benefits to the child and breast- or chest-feeding parent. For transgender women and nonbinary people on estrogen-based, gender-affirming hormone therapy, the ability to nourish their infants through production of their own milk may also be a profoundly gender-affirming experience. Two prior case studies have been published describing induced lactation in transgender women, but analysis of the nutritional quality of the milk produced has not been previously described. Here we describe the experience of a transgender woman who underwent successful induction of lactation in order to breastfeed her infant, who was gestated by her partner. Through modification of exogenous hormone therapy, use of domperidone as a galactogogue, breast pumping, and ultimately direct breastfeeding, the participant was able to co-feed her infant for the first 4 months of life. We provide a detailed description and timeline of the medications used, laboratory and electrocardiographic measurements, results of the participant's milk analysis showing robust macronutrient content, and description of the participant's experience in her own words. These findings provide reassurance about the adequacy of nutrition from human milk produced by non-gestational transgender female and nonbinary parents on estrogen-based, gender-affirming hormone therapy, and support the importance of this experience on a personal level.


Associations of water, sanitation, and hygiene with typhoid fever in case-control studies: a systematic review and meta-analysis.
Water, sanitation, and hygiene (WASH) play a pivotal role in controlling typhoid fever, as it is primarily transmitted through oral-fecal pathways. Given our constrained resources, staying current with the most recent research is crucial. This ensures we remain informed about practical insights regarding effective typhoid fever control strategies across various WASH components. We conducted a systematic review and meta-analysis of case-control studies to estimate the associations of water, sanitation, and hygiene exposures with typhoid fever. We updated the previous review conducted by Brockett et al. We included new findings published between June 2018 and October 2022 in Web of Science, Embase, and PubMed. We used the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for risk of bias (ROB) assessment. We classified WASH exposures according to the classification provided by the WHO/UNICEF Joint Monitoring Programme for Water Supply, Sanitation, and Hygiene (JMP) update in 2015. We conducted the meta-analyses by only including studies that did not have a critical ROB in both Bayesian and frequentist random-effects models. We identified 8 new studies and analyzed 27 studies in total. Our analyses showed that while the general insights on the protective (or harmful) impact of improved (or unimproved) WASH remain the same, the pooled estimates of OR differed. Pooled estimates of limited hygiene (OR = 2.26, 95% CrI: 1.38 to 3.64), untreated water (OR = 1.96, 95% CrI: 1.28 to 3.27) and surface water (OR = 2.14, 95% CrI: 1.03 to 4.06) showed 3% increase, 18% decrease, and 16% increase, respectively, from the existing estimates. On the other hand, improved WASH reduced the odds of typhoid fever with pooled estimates for improved water source (OR = 0.54, 95% CrI: 0.31 to 1.08), basic hygiene (OR = 0.6, 95% CrI: 0.38 to 0.97) and treated water (OR = 0.54, 95% CrI: 0.36 to 0.8) showing 26% decrease, 15% increase, and 8% decrease, respectively, from the existing estimates. The updated pooled estimates of ORs for the association of WASH with typhoid fever showed clear changes from the existing estimates. Our study affirms that relatively low-cost WASH strategies such as basic hygiene or water treatment can be an effective tool to provide protection against typhoid fever in addition to other resource-intensive ways to improve WASH. PROSPERO 2021 CRD42021271881.


Effect of heparin on membrane associated clathrin basketwork of cultured cells derived from the stromal-vascular fraction of mouse brown adipose tissue.
The effect of heparin treatment on clathrin basketwork of cell membranes was examined in cultured cells derived from the stromal-vascular fraction of neonatal mouse brown adipose tissue. The cytoplasmic surface of the plasma membrane of ruptured cells was examined with surface replicas. Heparin treatment significantly decreased the extent of clathrin basketwork associated with the membrane from 3.4 to 0.2%. The loss of clathrin basketwork suggests that heparin treatment of these cells affected intracellular sorting processes associated with endocytosis.


A scheme for the evaluation of methods in clinical chemistry with particular application to those measuring enzyme activities. Part I: general considerations.
A 20-point system is presented whereby commercially produced clinical chemistry procedures, i.e., in vitro diagnostic kits, may be assessed for adequacy of packaging, labelling and enclosed literature. Criteria are given for the selection of a reference method to use in the test method evaluation and the design of a patient comparison study using these two methods is described. The importance of standards and calibration materials as they relate to accuracy and specificity is discussed. A procedure for assessing accuracy by recovery studies is outlined. A method for the assessment of precision on a within-day and a day-to-day basis is described.


Legislative issues impacting on the practice of the South African nurse practitioner.
To present an overview of the impact of the nurse practitioner (NP) on the South African health care arena and describe the legislative framework for NP practice. Statutes and laws of the government of South Africa; published professional guidelines; authors' experiences. The key challenges for NPs in South Africa lie in lobbying for enabling legislation, obtaining access to education and training opportunities, and managing risks within the rapidly changing environment. Some aspects of the NP's accountability and responsibilities have as yet not been adequately addressed in the current legislative framework and will certainly increase the risk for malpractice. South African NPs will have to establish partnerships with important role players, not only in South Africa, but also internationally, to ensure that an enabling environment for quality health services is created.


Long-term exposure to air pollution and risk of SARS-CoV-2 infection and COVID-19 hospitalisation or death: Danish nationwide cohort study.
Early ecological studies have suggested links between air pollution and risk of coronavirus disease 2019 (COVID-19), but evidence from individual-level cohort studies is still sparse. We examined whether long-term exposure to air pollution is associated with risk of COVID-19 and who is most susceptible. We followed 3 721 810 Danish residents aged ≥30 years on 1 March 2020 in the National COVID-19 Surveillance System until the date of first positive test (incidence), COVID-19 hospitalisation or death until 26 April 2021. We estimated residential annual mean particulate matter with diameter ≤2.5 μm (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) in 2019 by the Danish DEHM/UBM model, and used Cox proportional hazards regression models to estimate the associations of air pollutants with COVID-19 outcomes, adjusting for age, sex, individual- and area-level socioeconomic status, and population density. 138 742 individuals were infected, 11 270 were hospitalised and 2557 died from COVID-19 during 14 months. We detected associations of PM2.5 (per 0.53 μg·m-3) and NO2 (per 3.59 μg·m-3) with COVID-19 incidence (hazard ratio (HR) 1.10 (95% CI 1.05-1.14) and HR 1.18 (95% CI 1.14-1.23), respectively), hospitalisations (HR 1.09 (95% CI 1.01-1.17) and HR 1.19 (95% CI 1.12-1.27), respectively) and death (HR 1.23 (95% CI 1.04-1.44) and HR 1.18 (95% CI 1.03-1.34), respectively), which were strongest in the lowest socioeconomic groups and among patients with chronic respiratory, cardiometabolic and neurodegenerative diseases. We found positive associations with BC and negative associations with O3. Long-term exposure to air pollution may contribute to increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection as well as developing severe COVID-19 disease requiring hospitalisation or resulting in death.


Isoconversional thermal decomposition reaction kinetics of oil palm trunk and rubberwood sawdust for thermochemical conversion processes.
Biomass as a raw material has profound implications for thermal conversion processes. It is important to study the relationship between kinetic modeling to depict significant importance in thermal processing by estimating volatile yield and reaction performance during biomass decomposition. This work aimed to determine the thermal decomposition reaction kinetics of non-woody (oil palm trunk (OPT)) and woody (rubberwood sawdust (RWS)) biomass. Devolatilization of biomass is determined by the thermogravimetric analysis (TGA) at three different heating rates (10, 20, and 30 °C/min) using nitrogen as inert gas. The kinetic analysis used isoconversion models of Friedman, Ozawa-Flynn-Wall (OFW), and Kissinger-Akahira-Sunose (KAS). The activation energy varied from 218.4 to 303.8 kJ/mol (Friedman), 235.9 to 299.1 kJ/mol (OFW), and 235.8 to 298.9 kJ/mol (KAS) for OPT; and 199.7 to 228.1 kJ/mol (Friedman), 210.6 to 225.6 kJ/mol (OFW), and 210.7 to 225.2 kJ/mol (KAS) for RWS. The kinetic analysis indicated that RWS and OPT had diverse reaction kinetics, which depend on the reaction rate and order of the reaction. Experimental and theoretical conversion data agreed reasonably well, indicating that these results can be used for future OPT and RWS process modeling. Consistency of results is validated using GC-MS equipped with a pyrolyzer.


Specific immunotherapy for non-curatively resected gastric cancer.
The prognosis of patients with advanced gastric cancer treated with non-curative resection is very poor. In order to improve patient prognosis, we have tried specific immunotherapy as an adjunct to surgery since January 1968. Sixty-two patients with gastric cancer underwent non-curative resection during the period of this study. Twenty-eight of these patients were treated with specific immunotherapy after surgery, and 34 patients received no additional therapy. The five year survival rate was 35 per cent in the former group, and zero in the latter. No significant difference in the degree of tumor extension and invasion was noted between the two patient groups. We concluded that specific immunotherapy as an adjunct to non-curative resection for advanced cancer is worthy of further study.


Sensitive detection of ferbam by coupling solid phase microextraction with surface enhanced Raman spectroscopy based on Au nano-glass capillary.
In this study, we developed an innovative approach that combines solid phase microextraction (SPME) with surface-enhanced Raman spectroscopy (SERS) to detect pesticide ferbam rapidly. An Au nano-glass capillary was fabricated by coating template-freely synthesized three-dimensional network Au nanostructures (3D-NW AuNSs) on the roughened surface of glass capillary and used for SPME and SERS respectively. Significant Raman signals were obtained by the SPME-SERS method, followed by detection of ferbam in water and orange juice samples with only 1 min SPME process. Results showed that Au nano-glass capillaries could achieve the detection of ferbam with limit of detection of 0.05 μg/L, and coefficient of determination (R2) of 0.9913. The recovery of predicted results was in the range of 88.46-103.29% and the relative standard deviation (RSD) was 3.5-8.2%. This study demonstrated potential capability of the SPME-SERS method for rapid (within 1 min) and sensitive detection of organic compounds in complex matrices. The SERS-active Au nano-glass capillary is easy to carry and operate, and is expected to play a role in the detection of trace pollutants.


The role of transcription factors in shaping regulatory T cell identity.
Forkhead box protein 3-expressing (FOXP3+) regulatory T cells (Treg cells) suppress conventional T cells and are essential for immunological tolerance. FOXP3, the master transcription factor of Treg cells, controls the expression of multiples genes to guide Treg cell differentiation and function. However, only a small fraction (<10%) of Treg cell-associated genes are directly bound by FOXP3, and FOXP3 alone is insufficient to fully specify the Treg cell programme, indicating a role for other accessory transcription factors operating upstream, downstream and/or concurrently with FOXP3 to direct Treg cell specification and specialized functions. Indeed, the heterogeneity of Treg cells can be at least partially attributed to differential expression of transcription factors that fine-tune their trafficking, survival and functional properties, some of which are niche-specific. In this Review, we discuss the emerging roles of accessory transcription factors in controlling Treg cell identity. We specifically focus on members of the basic helix-loop-helix family (AHR), basic leucine zipper family (BACH2, NFIL3 and BATF), CUT homeobox family (SATB1), zinc-finger domain family (BLIMP1, Ikaros and BCL-11B) and interferon regulatory factor family (IRF4), as well as lineage-defining transcription factors (T-bet, GATA3, RORγt and BCL-6). Understanding the imprinting of Treg cell identity and specialized function will be key to unravelling basic mechanisms of autoimmunity and identifying novel targets for drug development.


Technical Capabilities and Limitations of Optical Spectroscopy and Calorimetry Using Water-Miscible Solvents: The Case of Dimethyl Sulfoxide, Acetonitrile, and 1,4-Dioxane.
In drug development, water-miscible solvents are commonly used to dissolve drug substances. Typical routine procedures in drug development include dilution of the stock drug solution into an aqueous solution containing target macromolecules for drug binding assays. However, water-miscible solvents impose some technical limitations on the assays on account of their light absorption and heat capacity. Here, we examined the effects of the dilution of 3 water-miscible solvents, that is, dimethyl sulfoxide, acetonitrile, and 1,4-dioxane, on the baseline stability and signal/noise ratio in circular dichroism spectroscopy, isothermal titration calorimetry, and differential scanning calorimetry. Dimethyl sulfoxide and 1,4-dioxane affect the signal/noise ratio of circular dichroism spectra at typically used concentrations due to their light absorbance. The water-miscible solvents generate interfering signals in the isothermal titration calorimetry due to their mixing heat. They show negative or positive slope in the differential scanning calorimetry. Such interfering effects of the solvents are reduced by appropriate dilution according to the analytical techniques. Because the water-miscible solvents have solubilization capacity for alkyl chain moieties and aromatic moieties of chemicals, drug substances containing these moieties can be dissolved into the solvents and then subjected to the analyses to examine their interactions with target proteins after appropriate dilution of the drug solutions.


Focused microbiological surveillance and gram-negative beta-lactamase--mediated resistance in an intensive care unit.
To evaluate the use of focused surveillance in following resistance patterns within an intensive care unit (ICU). Antibiograms of 167 gram-negative isolates from ICU patients were compared to the hospitalwide antibiograms. ICU isolates were examined for the newer forms of beta-lactamase resistance. An outbreak of multiresistant Pseudomonas aeruginosa during the survey illustrated the usefulness of focused surveillance in early intervention and containment. A 700-bed adult tertiary care hospital with a 16-bed medical and surgical ICU. Hospitalwide and ICU antibiograms of the Enterobacteriaceae were similar. However, resistance of P aeruginosa in the ICU was underestimated by hospitalwide rates. Susceptibility of ICU isolates to ceftazidime, ciprofloxacin, and piperacillin was 54%, 54%, and 42%, compared with 81%, 77%, and 85%, respectively, in the hospital at large. Thirty-five percent of isolates exhibited one of the newer forms of beta-lactamase-mediated resistance, with 17% of isolates exhibiting Class I cephalosporinase production. Targeted survey of high antibiotic-use hospital units should be used to study bacterial epidemiology, rather than relying on general hospital data to evaluate patterns of antimicrobial resistance. Monitoring of potential problem areas leads to prompt identification of changes in resistance and allows early intervention.


Prognostic Factors of Rectal Cancer in Southern Iran.
Rectal cancer accounts for one-third of all colorectal cancer (CRC) cases. Due to physiological and anatomical differences, some researchers consider rectal cancer as a separate organ malignancy during the recent decades. However, limited studies have been conducted in this regard in Iran. Therefore, the aim of this study is to determine survival of rectal cancer and its, affecting factors in Fars province, southern Iran. In this cohort study, we used the data of 387 patients with rectal cancer gathered by the Colorectal Research Center of Shiraz University of Medical Sciences between 2007 and 2015. The impact of 35 explanatory factors including demographic information, medical history, pathologic data, and imaging findings was evaluated using Cox regression analysis. Out of all patients, 111 ones (29%) died. The median follow-up period was 36 months. The patients' mean age at diagnosis was 56.72 ± 13.89 years. Their 5-year survival was 65% (95% CI: 58-69%). The results of multiple Cox regression analysis showed that sex (male/female; HR = 1.73, 95% CI: 1.15-2.67), vascular invasion (yes/no; HR = 2.40, 95% CI: 1.45-3.99), and lymph node ratio (> 0.2 vs ≤ 0.2; HR = 2.19, 95% CI: 1.41-3.40) were significantly correlated to survival. Various geographical parts of Iran show different rates regarding rectal cancer survival. A better 5-year survival rate was detected by this study for the patients with rectal cancer in Fars province, southern Iran, compared to many parts of the country. Moreover, gender, vascular invasion, and nodal status played an important role in survival of rectal cancer.


The value of high-dose chemotherapy in patients with first relapsed Ewing sarcoma.
Prognosis of patients with relapsed Ewing sarcoma (ES) is poor. The 5-year overall survival (OS) is 13%. We analyzed high-dose chemotherapy (HDtx) versus conventional chemotherapy (CHtx) in patients with relapsed ES. Data from 239 patients with first relapse, registered during 2000-2011 in the ES relapse registry of the Cooperative Ewing Sarcoma Study Group (CESS) were analyzed. Of 239 patients, 200 received various non-HDtx second-line CHtx regimens. Seventy-three patients had additional HDtx followed by autologous stem cell rescue. The 2-year event-free survival (EFS) was 10% (SE = 0.02) in patients treated without HDtx and 45% (SE = 0.09) in patients treated with HDtx. In a second step, we focused on those patients who achieved complete remission (CR) or partial remission (PR) after four to six cycles of conventional second-line CHtx. Here, the 2-year EFS was 31% (SE = 0.08) without additional HDtx and 44% (SE = 0.09) with additional HDtx. In addition, multivariate regression analysis indicates absence of HDtx treatment, with a Hazard ratio (HR) of 2.90 (95% CI 1.41-6.0), and early relapse, with a HR of 4.76 (95% CI 2.31-9.78), as independent prognostic factors for EFS. Additional HDtx may contribute to further reduce the risk of further events in patients who respond to conventional second-line CHtx.


Comparison of prekeratin and keratin polypeptides in normal and psoriatic human epidermis.
High-resolution electrophoresis has been used to extend previous observations on the polypeptide composition of keratins in psoriatic epidermis. We have compared psoriatic scale keratins with normal and with scale extracts from several different epidermal disorders. Uninvolved psoriatic epidermis contained prekeratin and keratin of normal profile (68, 60, 58, 52 kDa and 66, 58, 55 kDa, respectively). Prekeratin from involved psoriatic epidermis showed a variable quantitative reduction in the 68-kDa polypeptide and an altered expression of smaller polypeptides (Mr 40 000-55 000). Keratin from the psoriatic lesion was abnormal and appeared 'prekeratin-like'. Keratin from the involved stratum corneum of patients with seborrhoeic eczema. Darier's disease and common dandruff were also similar to prekeratin, but that from ichthyosis and toxic epidermal necrolysis was normal. These results suggest that psoriatic keratinocytes have a defective but variable expression of prekeratin polypeptides. Furthermore, the differentiation-linked modification of prekeratin to keratin is defective in psoriasis, a phenomenon found in other hyperkeratotic epidermal disorders.


Cell-mediated immune functions, interleukin 2 and interferon production by high leukemia incidence mutant (hr/hr) mice of the HRS/J strain.
Homozygous hr/hr mice of the HRS/J strain have a high incidence of lymphoma not seen in congenic hr/+ littermates. The suggestion has been made that a helper T cell defect in the immune system of the homozygotes may account for this. To further examine the immune status of these mice, we compared the ability of spleen cells of mice of both types to stimulate, as well as to generate, allogeneic cell-mediated cytolytic responses and to produce a soluble mediator of such responses. In addition, both types of mice were tested for their ability to produce interferon (IFN) or to have their splenic natural killer cell (NK) levels augmented by polyriboinosinic-polyribocytidylic acid (poly rI-rC). We found that the spleen cells of young or aging mice of either type were able to stimulate the generation of alloreactive cytotoxic cells, but they did not inappropriately stimulate the generation of syngeneic cytotoxic cells. Similarly, spleen cells of both types of mice produced a T helper cell-derived growth factor (interleukin 2) involved in the proliferation of cytolytic cells and generated a classical cell-mediated lympholysis (CML) response to alloantigen-bearing cells. Finally, spontaneous NK cell levels, as well as poly rI-rC augmented IFN and NK cell levels, were similar in both types of mice. Thus, it appears that if defects in the immune system are solely responsible for the high incidence of lymphoma in hr/hr mice, the defects involve components or regulatory aspects of that system that have yet to be defined.


Early-onset malignant phyllodes breast tumor in a patient with germline pathogenic variants in NF1 and BRCA1 genes.
We present a 24-year-old female patient affected by neurofibromatosis type 1 (NF1) who developed a malignant phyllodes tumor of the breast. The molecular studies showed that the patient carried a heterozygous inactivating deleterious variant in BRCA1 inherited from the father associated with a germline de novo pathogenic alteration in NF1; the tumor presented a biallelic inactivation of both genes. Therefore, tumor analyses helped to establish that the germline NF1 and BRCA1 variants were in cis on the paternal chromosome. This last information is important to provide adequate genetic counselling regarding the risk of recurrence in the offspring, as well as opportunity for early intervention. In conclusion, we present the first case of a malignant phyllodes tumor of the breast in patient carrying pathogenic variants in NF1 and BRCA1. Further studies will be necessary to understand if the phyllodes histotype represents a very rare component of NF1-associated breast cancer.


A comparison between the prostaglandin releasing effects of angiotensin II and angiotensin III.
Angiotensin II and its natural fragment (des-aspartic acid)1-angiotensin II (angiotensin III) induced a dose-dependent contraction in the isolated rat stomach fundus strip and rat colon. 1-Acetyl-2-(8-chloro-10,11-dihydrodibenz(b,f)(1,4)oxazepine-10, carbonyl) hydrazine (SC 19220), a widely used competitive-blocker of prostaglandins and acetyl salicylic acid, a well-known inhibitor of prostaglandin biosynthesis, partially abolished the contraction induced by both peptides in the rat stomach fundus but not in the rat colon. The inhibition induced by SC 19220 and acetyl salicylic acid was found to be higher for angiotensin III than angiotensin II when the dose-response curves and equipotent concentrations of the peptides were compared before and after the drugs. These results were taken as evidence that some component of the contractile effects of angiotensin II and angiotensin III on the isolated rat stomach fundus involves the release of prostaglandins by the peptides and in this respect angiotensin III has higher potency than angiotensin II.


Vegetation and arthropod responses to wastewater enrichment of a pine forset.
The effects of spraying secondary-treated wastewater on a young pine forest were studied in South Carolina, U.S.A. Soil, herb-shrub layer vegetation and arthropods were analyzed in control, low-spray and high-spray areas to determine the overall impact of four years of chronic nutrient and water enrichment. Spraying had no significant effect on soil organic matter and cation exchange capacity. Soil cation buildups did not occur and cation leaching was evident.Wastewater application produced a more mesic environment and the herb-shrub layer vegetation shifted to an earlier stage in succession. Plant diversity decreased significantly as a few rapidly-growing opportunistic species (e.g., Erechtites hieracifolia, Polygonum pensylvanicum) replaced the more diverse perennial herbshrub layer vegetation of the pine forest. Peak vegetation biomass levels doubled and net primary production rates were 10 times greater in high spray areas. Litter biomass levels, however, did not change significantly. Litter decomposition rates were significantly greater in treated areas which apparently offset the added litter resulting from increased plant production.Arthropod production increased 3-fold in treated areas. All herbivore guilds had higher biomasses that reflected seasonal changes in producer phenology. Total arthropod diversity increased despite the lower vegetation diversity in spray areas. Arthropod diversity apparently increased because of greater resource availability in treated areas.


Determination and uptake of abamectin and difenoconazole in the stingless bee Melipona scutellaris Latreille, 1811 via oral and topic acute exposure.
Bees are considered as important providers of ecosystem services, acting via pollination process in crops and native plants, and contributing significantly to the maintenance of biodiversity. However, the decrease of bee's population has been observed worldwide and besides other factors, this collapse is also related to the extensive use of pesticides. In this sense, studies involving the assessment of adverse effects and the uptake of pesticides by bees are of great concern. This work presents an analytical method for the determination of the insecticide abamectin and the fungicide difenoconazole in the stingless bee Melipona scutellaris exposed via oral and topic to endpoints concentrations of active ingredients (a.i.) alone and in commercial formulations and the discussion about its mortality and uptake. For this purpose, QuEChERS (Quick, Easy, Cheap, Efficient, Rugged and Safe) acetate modified method was used for extraction and pesticides were determined by LC-MS/MS. The validation parameters have included: a linear range between 0.01 and 1.00 μg mL-1; and LOD and LOQ of 0.038 and 0.076 μg g-1 for abamectin and difenoconazole, respectively. The uptake of tested pesticides via oral and topic was verified by the accumulation in adult forager bees, mainly when the commercial product was tested. Mortality was observed to be higher in oral exposure than in topic tests for both pesticides. For abamectin in a commercial formulation (a.i.) no differences were observed for oral or topic exposure. On the other hand, for difenoconazole, topic exposure had demonstrated higher accumulation in bees, according to the increase of received dose. Through the results, uptake and the possible consequences of bioaccumulated pesticides are also discussed and can contribute to the knowledge about the risks involving the exposure of bees to these compounds.


Hip anatomic variants that may mimic pathologic entities on MRI: nonlabral variants.
The hip has several anatomic variants that may be mistaken for pathologic abnormalities. The radiologist needs to be able to distinguish these variants from true abnormalities. In this review, we present nonlabral variants of the hip that can be seen on MRI. The hip has multiple anatomic variants that may mimic disease on hip MRI. Like labral variants, nonlabral variants can be confused for true abnormalities.


A day in the life of a G protein-coupled receptor: the contribution to function of G protein-coupled receptor dimerization.
G protein-coupled receptors are one of the most actively studied families of proteins. However, despite the ubiquity of protein dimerization and oligomerization as a structural and functional motif in biology, until the last decade they were generally considered as monomeric, non-interacting polypeptides. For the metabotropic glutamate-like group of G protein-coupled receptors, it is now firmly established that they exist and function as dimers or, potentially, even within higher-order structures. Despite some evidence continuing to support the view that rhodopsin-like G protein-coupled receptors are predominantly monomers, many recent studies are consistent with the dimerization/oligomerization of such receptors. Key roles suggested for dimerization of G protein-coupled receptors include control of protein maturation and cell surface delivery and providing the correct framework for interactions with both hetero-trimeric G proteins and arrestins to allow signal generation and its termination. As G protein-coupled receptors are the most targeted group of proteins for the development of therapeutic small molecule medicines, recent indications that hetero-dimerization between co-expressed G protein-coupled receptors may be a common process offers the potential for the development of more selective and tissue restricted medicines. However, many of the key experiments have, so far, been limited to model cell systems. Priorities for the future include the generation of tools and reagents able to identify unequivocally potential G protein-coupled receptor hetero-dimers in native tissues and detailed analyses of the influence of hetero-dimerization on receptor function and pharmacology.


Introducing the thin and ultrathin submental artery perforator flaps for precise reconstruction following T1-2 oral cavity cancer resection.
We reported a case series of thin (n = 32) and ultrathin (n = 4) submental artery perforator flaps (SMAPF) for precise reconstruction following T1-2 oral cavity cancer resection. The former is indicated for tongue reconstruction involving the tongue tip, and buccal lining replacement involving the mouth corner, while the latter is specifically tailored to restore superficial buccal defects after resection of small early cancer originating from oral submucous fibrosis. All flaps survived. Most flap reconstructions reached satisfactory cosmetic results. Based on this series, we discussed the indications of thin and ultrathin SMAPFs in intaoral reconstruction, and surgical tips for flap thinning.


Effects of metabolic inhibitors on activity of Cry1Ab toxin to inhibit growth of Ephestia kuehniella larvae.
Although the toxins of Bacillus thuringiensis Berliner (Bt) are frequently used to control lepidopteran pests, the tolerance or resistance of some lepidopteran moth strains may limit Bt applications. In this study, insecticidal cocktails consisting of sublethal doses of Cry1Ab toxin and additive compounds were tested for their suppressive effect on larval relative growth rate (RGR) in Ephestia kuehniella Zeller under laboratory conditions. In the first step, the suppressive effect of diflubenzuron, soybean trypsin inhibitor (STI) and chitinase on RGR was confirmed. In the second step, these compounds were incorporated into a mixture of crushed kernels of Bt maize hybrid MON 810-YieldGard and its isoline with concentrations of Cry1Ab toxin ranging from 0.011 to 0.091 microg g(-1) diet. An additive effect on the suppression of larval RGR in E. kuehniella was found in a combination of diflubenzuron, STI and STI + chitinase as secondary compounds in insecticidal cocktails. Chitinase showed no additive effect on RGR. The highest suppression level was found in cocktails with STI + chitinase as a secondary compound. It is hypothesized that the protease inhibitor (STI) protects both chitinase and Cry1Ab proteins from endogenous proteases in the larval midgut and prolongs their insecticidal activities. The possible application of insecticidal cocktails in the control of E. kuehniella is discussed.


Patient-based low dose cone beam CT acquisition settings for prostate image-guided radiotherapy treatments on a Varian TrueBeam linear accelerator.
To evaluate the performance of low dose cone beam CT (CBCT) acquisition protocols for image-guided radiotherapy of prostate cancer. CBCT images of patients undergoing prostate cancer radiotherapy were acquired with the settings currently used in our department and two low dose settings at 50% and 63% lower exposure. Four experienced radiation oncologists and two radiation therapy technologists graded the images on five image quality characteristics. The scores were analysed through Visual Grading Regression, using the acquisition settings and the patient size as covariates. The low dose acquisition settings have no impact on the image quality for patients with body profile length at hip level below 100 cm. A reduction of about 60% of the dose is feasible for patients with size below 100 cm. The visibility of low contrast features can be compromised if using the low dose acquisition settings for patients with hip size above 100 cm. Low dose CBCT acquisition protocols for the pelvis, based on subjective evaluation of patient images.


Enantioselective semireduction of allenes.
Rh-hydride catalysis solves a synthetic challenge by affording the enantioselective reduction of allenes, thereby yielding access to motifs commonly used in medicinal chemistry. A designer Josiphos ligand promotes the generation of chiral benzylic isomers, when combined with a Hantzsch ester as the reductant. This semireduction proceeds chemoselectively in the presence of other functional groups, which are typically reduced using conventional hydrogenations. Isotopic labelling studies support a mechanism where the hydride is delivered to the branched position of a Rh-allyl intermediate.Reduction of allenes poses several challenges in terms of chemo-, regio- and enantio-selectivity. Here, the authors report a rhodium-Josiphos catalytic system that reduces a variety of aryl allenes to chiral benzylic compounds with excellent selectivity and functional group tolerance.


Covalent Immobilization of Polypeptides on Polylactic Acid Films and Their Application to Fresh Beef Preservation.
To enhance the advantage of a long-term stability and low-toxicity active packaging system, two biodegradable covalent immobilized antibacterial packaging films were developed and applied to fresh beef preservation in this study. A polylactic acid (PLA) film was prepared by the extrusion-casting method. The surface of the PLA film was modified with plasma treatment to generate carboxylic acid groups, and then antibacterial agent nisin or ε-poly lysine (ε-PL) was covalently attached to the modified film surface. Physical, chemical, and antimicrobial properties of films were then characterized. Scanning electron microscopy and water contact angle images confirmed that nisin or ε-PL was successfully grafted onto the film surface. The values of protein loading on the nisin-g-PLA film and ε-PL-g-PLA film were 5.34 ± 0.26 and 3.04 ± 0.25 μg of protein/cm2 on the surface. Microbial analysis indicated that the grafted films effectively inhibit the growth of bacteria. Finally, the effects of the nisin-g-PLA film or ε-PL-g-PLA film on physicochemical changes and microbiological counts of fresh beef during cold storage at 4 °C were investigated. The total viable count of the control sample exceeded 7 logarithms of the number of colony forming units per gram (log CFU/g) after 11 days of cold storage (7.01 ± 0.14 log CFU/g) versus 15 days for the ε-PL-g-PLA film (7.37 ± 0.06 log CFU/g) and the nisin-g-PLA film (6.83 ± 0.10 log CFU/g). The results showed that covalent immobilized antibacterial packaging films had positive impacts on the shelf life and quality of fresh beef. Therefore, a covalent immobilized antibacterial packaging system could be a novel preservative method for foods.


Detection of Amyloid-β(1-42) Aggregation With a Nanostructured Electrochemical Sandwich Immunoassay Biosensor.
Amyloid-β(1-42) [Aβ(1-42)] oligomer accumulations are associated with physiologic alterations in the brains of individuals with Alzheimer's disease. In this study, we demonstrate that a nanostructured gold electrode with deposited gold nanoparticles, induced via electrochemical impedance spectroscopy (EIS), may be used as an Aβ(1-42) conformation biosensor for the detection of Alzheimer's disease. Monoclonal antibodies (12F4) were immobilized on self-assembled monolayers of the electrochemical sandwich immunoassay biosensor to capture Aβ(1-42) monomers and oligomers. Western blot and fluorescence microscopy analyses were performed to confirm the presence of Aβ(1-42) monomers and oligomers. EIS analysis with an equivalent circuit model was used to determine the concentrations of different Aβ(1-42) conformations in this study. We identified conformations of Aβ(1-42) monomers and Aβ(1-42) oligomers using probe antibodies (12F4) by employing EIS. R Aβ ( 1 - 42 ) indicates the sum resistance of impedance measured during Aβ(1-42) immobilization. Δ R 12 F 4 refers to the concentration of probe antibody (12F4) binding with Aβ(1-42). The concentration of Aβ(1-42) oligomer was defined as the percentage of Aβ(1-42) aggregation R 12 F 4 / R Aβ ( 1 - 42 ) . The experimental results show that the biosensor has high selectivity to differentiate Aβ(1-40) and Aβ(1-42) monomers and Aβ(1-42) oligomers and that it can detect Aβ(1-42) oligomer accurately. The linear detection range for Aβ(1-42) oligomers was between 10 pg/ml and 100 ng/ml. The limit of detection was estimated to be 113 fg/ml.


Effects of hospital-to-home transitional care on health outcomes of elderly patients in Islamic Republic of Iran.
Hospitalization has a negative effect on the functional and clinical outcomes of elderly patients. To evaluate the effect of a care transition intervention on functional and clinical outcomes and quality-of-life of elderly patients in the Islamic Republic of Iran after hospital discharge during a 3-month follow-up. We conducted a randomized controlled trial of 304 elderly hospitalized patients in Tehran from December 2018 to January 2020. The intervention group (n = 152) received care transition intervention and the control group (n = 152) received routine hospital discharge. All patients were assessed during hospital stay and at 30, 60 and 90 days after hospital discharge. Participants were evaluated using the Minimum Data Set-Home Care form, which assesses daily living activity, instrumental daily living activity, cognitive performance, cognition, pain, and depression. Rehospitalization and qualityof- life were evaluated, and differences between the groups and trends in quality-of-life were assessed. Only instrumental daily living activity in the functional outcomes and quality-of-life were greater in the intervention group than the controls. The intervention (odds ratio (OR): 0.11; 95% confidence intervals (CI): 0.01-0.97), age (OR: 1.16; 95% CI: 1.01-1.33), and cognition (OR: 1.24; 95% CI: 1.02-1.51) predicted instrumental daily living activity. Age (coefficient: -0.009, P = 0.001), depression (coefficient: -0.157; P < 0.001), cognition (coefficient: -0.023, P < 0.001) and pain (coefficient: -0.106, P = 0.007) predicted quality-of-life. Care transition interventions can help maintain the independence of older adults after hospital discharge and improve their quality-of-life.


In utero diagnosis of intrapericardial teratoma: a case for in utero open fetal surgery.
We present a case of intrapericardial teratoma diagnosed by ultrasound at 26 weeks of gestation presenting as a large tumour mass and rapid development of hydrops fetalis. The fetus died in utero one day before scheduled open fetal surgery.


"Only a manic depressive!": the zone of the untouchable and exceeding limits in acute psychiatric care.
This article addresses psychotic patients' fragile boundaries and need for professional help to restore their personal untouchable zone. We examine how nurses move into this inviolable zone and re-establish limits. Empirical data are drawn from an acute psychiatric setting and focus on one patient in different situations and on her relationships with nurses. Data from nurses' discussions and the researcher's experience are also included. The concept of the zone of the untouchable, by the Danish theologian and philosopher K. E. Løgstrup, guides interpretation. Analysis shows how and with which critical and constructive consequences the diagnosis-oriented understanding affects the patient-nurse relationship. Conclusions include premises that can guide nurses moving into the patient's untouchable zone.


Long-term in vitro suspension culture of Toxoplasma and HeLa cells.
To establish a method of mass and long-term propagation of Toxoplasma in suspension cultures and to find a technique for separating the organisms from host cells, basic investigations were carried out in a microcomputer controlled system. By using an arbitrary unit "the medium index" host HeLa cells were continuously supplied to Toxoplasma organisms for about 30 days, at cycles of 4 days. HeLa cells were well infected with Toxoplasma in the suspension cultures by leaving the medium unstirred for 15 min intervals. The separation of Toxoplasma organisms from cells was improved by treating toxoplasmas and HeLa cells mixtures with 0.4% trypsin. The total number of separated organisms obtained from 29 days cultivation period was 4.9 X 10(9). The mean generation time of Toxoplasma organisms on the 0, 10, 20 and 30 day's cultivation was calculated approximately 7.4, 9.4, 9.3 and 7.8 h, respectively.


Self-Preservation in Both Sides: Pathology of Spiritual Care in Iran.
The aim of this study was to create a deeper understanding of the variables that may restrain or progress spiritual care in Iran. This manuscript provides an in-depth description of barriers to delivering spiritual care by nurses as well as patients' compensatory mechanisms against deprivation from spiritual care termed "self-preservation in both sides" emerged from an empirical study. It brings issues such as structural, hierarchical, social and personal concerns, which may prevent advancing spirituality within health care, to light. Thirty-five participants, nurses (n = 10), patients (n = 22) and their relatives (n = 3), took part in this study, and data were analyzed using qualitative content analysis method. Being aware of these results may help nurses and healthcare professionals to engage with and overcome some of the structural, hierarchical and social variables affecting spiritual care.


Biotin uptake: influx, efflux and countertransport in Escherichia coli K12.
Biotin uptake by Escherichia coli K12 has been reinvestigated. The vitamin uptake is an active process depending on energy and inhibited by uncouplers. The kinetic parameters (Km = 0.27 microM, Vmax = 6.8 pmol/min per mg dry cells) are close to those previously determined for a biotin-dependent strain E. coli C162 (Piffeteau, A., Zamboni, M. and Gaudry, M. (1982) Biochim. Biophys. Acta 688, 29-36). By use of biotin p-nitrophenyl ester, an affinity label of the biotin transport system, it was shown, under conditions of steady state, that the efflux of biotin is not energy dependent and is mainly mediated by a diffusion mechanism. Reexamination of the regulation of the biotin transport by biotin, revealed that only 50% of the biotin uptake system is under control by the vitamin.


Effects of prednisolone on behavioral and inflammatory profile in animal model of PTZ-induced seizure.
Epilepsy is a chronic neurological condition that affects 1%-2% of the world population. Although research about the disease is advancing and a wide variety of drugs is available, about 30 % of patients have refractory epilepsy which cannot be controlled with the most common drugs. This highlights the need for a better understanding of the disorder and new types of treatment for it. Against this backdrop, a growing body of evidence has reported that inflammation may play a role both in the origin and in the progression of seizures. It has shown a tendency to be both the root and the result of epilepsy. This investigation aimed to assess the impact of prednisolone, a steroidal anti-inflammatory drug, in an animal model of pentylenetetrazole (PTZ)-induced seizures, at 1 mg/kg and 5 mg/kg doses. We also examined the degree of seizure severity and the modulation of pro-inflammatory cytokines in the treated animals. Four treatment groups were used (saline, diazepam, prednisolone 1 mg/kg, and prednisolone 5 mg/kg) and, in addition to their own daily treatments, subconvulsant doses of pentylenetetrazole (25 mg/kg) were administered every other day during a test protocol that lasted 14 days. After treatment, the cytokines interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured in the animals' sera, hippocampi, and prefrontal cortices. Animals treated with prednisolone presented less severe seizures than the animals in the saline group, and there was a decrease in pro-inflammatory cytokine levels in central structures, but not peripheral ones. In short, an animal model of chemically-induced epileptic seizures was used, in which the animals were treated with doses of prednisolone, and these animals presented less severe seizures than the negative control group (saline), in addition to showing decreased levels of pro-inflammatory cytokines IL-6, IL-1β and TNF-α, in the hippocampi and prefrontal cortices, but not the sera.


[Endoscopic full-thickness resection].
Conventional endoscopic resection techniques such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) are powerful tools for the treatment of gastrointestinal (GI) neoplasms. However, those techniques are limited to the superficial layers of the GI wall (mucosa and submucosa). Lesions without lifting sign (usually arising from deeper layers) or lesions in difficult anatomic positions (appendix, diverticulum) are difficult - if not impossible - to resect using conventional techniques, due to the increased risk of complications. For larger lesions (>2 cm), ESD appears to be superior to the conventional techniques because of the en bloc resection, but the procedure is technically challenging, time consuming, and associated with complications even in experienced hands. Since the development of the over-the-scope clips (OTSC), complications like bleeding or perforation can be endoscopically better managed. In recent years, different endoscopic full-thickness resection techniques came to the focus of interventional endoscopy. Since September 2014, the full-thickness resection device (FTRD) has the CE marking in Europe for full-thickness resection in the lower GI tract. Technically the device is based on the OTSC system and combines OTSC application and snare polypectomy in one step. This study shows all full-thickness resection techniques currently available, but clearly focuses on the experience with the FTRD in the lower GI tract.


Effects of chronic vanadate administration in the STZ-induced diabetic rat. The antihyperglycemic action of vanadate is attributable entirely to its suppression of feeding.
Vanadate treatment can lower glycemia in diabetic rats. This action is generally attributed to vanadate's insulinomimetic properties, but vanadate also inhibits feeding, which could lower blood glucose. We therefore assessed the contribution of hypophagia to vanadate's antihyperglycemic action in a 3-week study of streptozocin-induced (STZ) diabetic rats. Untreated diabetic rats (n = 8) ate 54% more food than nondiabetic control rats (P < 0.001). Diabetic rats given sodium metavanadate (0.5 mg in 0.5 ml of water by gavage twice daily; n = 8) had significantly lower food intakes (P < 0.001) than untreated diabetic rats. In vanadate-treated diabetic rats, blood glucose levels were significantly lower than in untreated diabetic rats (P < 0.001). Untreated diabetic rats pair-fed to the food intake of the vanadate-treated diabetic rats (n = 8) showed virtually identical blood glucose falls (P > 0.05 vs. vanadate-treated diabetic rats). Vanadate treatment did not affect plasma insulin concentrations in diabetic rats. In nondiabetic rats (n = 8), vanadate treatment significantly reduced food intake (P < 0.05) and also lowered plasma insulin concentrations (P < 0.05) without significantly affecting glycemia. To investigate the mechanism of vanadate's hypophagic effect, we also measured regional hypothalamic levels of neuropeptide Y (NPY), a potent central appetite stimulant that is thought to drive hyperphagia in STZ-induced diabetes. Hypothalamic NPY concentrations rise markedly in diabetes and are normalized by insulin replacement. Unlike insulin, vanadate treatment did not normalize regional hypothalamic NPY concentrations in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Nonmelanoma skin cancer in the setting of erosive pustular dermatosis of the scalp: A case series and comment on management implications.
Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory cutaneous disorder typically affecting sun-damaged skin of mature individuals. Clinical features of EPDS include sterile pustules and chronic crusted erosions that can be hyperkeratotic and lead to scarring alopecia, atrophy, and telangiectasia. While the condition occurs on sun-damaged skin, a relationship with non-melanoma skin cancer (NMSC) has not been investigated. Here we attempted to identify cases of NMSC developing in the setting of EPDS. Retrospective review of EPDS cases in a dermatology practice. Six patients with mean (range) age 82 (65-92) years that developed NMSC in the setting of EPDS are reported. Five patients had skin phototype I or II associated with substantial solar elastosis. Four patients had history of NMSC. Four patients developed squamous cell carcinoma and two patients basal cell carcinoma on the scalp in the setting of EPDS. A morphologic change in an EPDS lesion, such as a crusted plaque becoming nodular and/or growing significantly within a relatively short period of time, prompted a biopsy that revealed NMSC. NMSC may develop in the setting of EPDS. Possible mechanisms underlying this association include the chronic inflammation associated with EPDS and ultraviolet light exposure. It is crucial to promptly obtain a biopsy in EPDS cases showing signs suspicious for NMSC. Further studies are required to confirm whether NMSC shows a higher prevalence in the setting of EPDS.


5-HTTLPR and BDNF Val66Met polymorphisms and response to rTMS treatment in drug resistant depression.
Repetitive transcranial magnetic stimulation (rTMS) is a painless and safe brain stimulation technique that has been found to be effective in treating depression symptoms. The potential usefulness of rTMS, in particular to treat drug resistant patients, might be increased by identifying genetic predictors of efficacy. According to this rationale, we investigated the role of two functional polymorphisms in the genes coding for the serotonin transporter (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF Val66Met), and rTMS response in a group of 36 drug resistant patients affected by mood disorders. rTMS treatment significantly improved depression symptomatology (p<0.0001) and the response was significantly greater in 5-HTTLPR LL homozygotes compared to S allele carriers (p=0.007) and in BDNF Val/Val homozygotes compared to Met allele carriers (p=0.024). These findings provide evidences about the involvement of both polymorphisms in rTMS antidepressant response. Further investigations in larger samples are needed to clarify the usefulness of 5-HTTLPR and BDNF Val66Met genotyping in the optimization of non-pharmacological treatments in mood disorders.


Tension pneumopericardium in blunt thoracic trauma.
Pneumopericardium, defined as the presence of gas in the pericardial sac, is a rare condition caused mostly by trauma. Tension pneumopericardium is a cause of hemodynamic instability; hence, it consists in a life-threatening situation and should be regarded in blunt chest trauma. A 51-year-old male was victim of a 4m fall and burial. He was stable upon admission and presented a simple pneumopericardium and pneumomediastinum on CT. While being submitted to an upper digestive endoscopy he presented respiratory failure and had to be intubated, suddenly evolving to shock. He was promptly referred to the operating room; a pericardial window confirmed tension pneumopericardium and immediately hemodynamic stability was restored. A pericardial drain was placed and kept for 15days. He was discharged at the 18th day post-trauma after a satisfactory recovery at the trauma ICU. Blunt thoracic trauma causes pneumopericardium by various mechanisms. Tension pneumopericardium is a possible outcome, probably related to positive-pressure ventilation. It leads to hemodynamic instability and requires immediate decompression and placement of a pericardial drain.


Postmenopausal women with carotid atherosclerosis: potential role of the serum calcium levels.
Studies on the association between serum calcium levels and cardiovascular diseases suggested a causative role for hypercalcemia but other studies showed that even serum calcium levels within normal range could be involved in atherosclerosis. However, while dietary calcium intake does not seem to be related to adverse cardiovascular effects, the association between calcium supplementation and the cardiovascular events has not been fully proven. Our aim was to determine the relation between serum calcium levels, within normal range, and the presence of carotid atherosclerosis in a population in whom investigations on this topic are lacking, the postmenopausal women. In this retrospective study, participants were recruited from women aged 49-65 years who underwent an ultrasonography evaluation of the carotid arteries between years 2008-2012. The study included 413 subjects with serum calcium level available, without symptomatic cardiovascular disease. A physical examination, including the evaluation of body mass index, waist and hip circumferences and the blood pressure, as well as, a collection of a venous blood sample was performed. The mean age was 56 ± 7 years. The prevalence of the carotid atherosclerosis was 50.8%. The comparison between women with and without carotid atherosclerosis showed differences for the classical risk factors and for serum calcium levels (p = 0.001). The logistic regression analysis, adjusting for these risk factors, confirmed the association between serum calcium levels and carotid atherosclerosis (p = 0.011). Furthermore, we showed an increasing prevalence of carotid atherosclerosis from lower to higher calcium quartiles (p = 0.016). We found a positive relation between serum calcium levels and the carotid atherosclerosis in postmenopausal women. This study may suggest a redetermination of the reference range of calcemia, at least in menopause.


Six-month treatment with atypical antipsychotic drugs decreased frontal-lobe levels of glutamate plus glutamine in early-stage first-episode schizophrenia.
To study the effects of treatment with atypical antipsychotic drugs on brain levels of glutamate plus glutamine in early-stage first-episode schizophrenia. Sixteen patients (eight males, eight females; aged 30 ± 11 years) completed the study. We used administered 6 months of atypical antipsychotic drugs and used proton magnetic resonance spectroscopy to evaluate the results. We found that the administration of atypical antipsychotic drugs for 6 months decreased the glutamate plus glutamine/creatine ratio in the frontal lobe. These results suggest that the administration of atypical antipsychotic drugs for at least 6 months decreased glutamatergic neurotransmissions in the frontal lobe in early-stage first-episode schizophrenia, but there was no difference in frontal-lobe levels between patients and control subjects before administration. Taking these findings into account, the glutamatergic and GABAergic neurons are implicated in early-stage first-episode schizophrenia, but in complex ways.


Search of the human proteome for endomorphin-1 and endomorphin-2 precursor proteins.
Based on the promising opioid pharmacological profile of the peptide, Tyr-Pro-Trp-Gly-NH(2) (Tyr-W-MIF), Zadina et al. [Zadina, J.E., Hackler, L., Ge, L.-J., Kastin, A.J., 1997. A potent and selective endogenous agonist for the mu-opiate receptor. Nature 386, 499-5502] synthesized and screened other Gly(4)-substituted peptides, culminating in the synthesis of Tyr-Pro-Trp-Phe-NH(2) (endomorphin-1), which displayed high affinity and selectivity for the mu-opioid receptor. The amidated peptide was then isolated from bovine brain frontal cortex, as was a related peptide, Tyr-Pro-Phe-Phe-NH(2) (endomorphin-2), that displayed similar high affinity and selectivity for the mu-opioid receptor. The biosynthesis of the endomorphins in the brain remains obscure, since the putative precursor proteins for the peptides have not been identified. With the completion of the human genome sequencing project, we hypothesized that we should uncover the biological precursors of the peptides using a bioinformatic approach to search the current human proteome for proteins that contained the endomorphin peptide sequences followed by Gly-Lys/Arg, the consensus sequence for peptide alpha-amidation and precursor cleavage. Twelve proteins were identified that contained the endomorphin-1 Tyr-Pro-Trp-Phe sequence, however none contained the Tyr-Pro-Trp-Phe-Gly sequence necessary for alpha-amidation. Twenty-two distinct proteins contained the endomorphin-2 tetrapeptide sequence, and two of those contained the sequence, Tyr-Pro-Phe-Phe-Gly, however, none contained the requisite peptide-Gly-Lys/Arg sequence. Western blot analysis using an endomorphin-2 antibody detected 4 prominent proteins in mouse brain, necessitating reinterpretation of previous immunocytolocalization studies in the brain. Screening of the current human proteome yielded no evidence for endomorphin precursor proteins based on accepted biochemical criteria.


Regional with urban-rural variation in low birth weight and its determinants of Indian children: findings from National Family Health Survey 5 data.
Low birth weight is a key indicator for child health, especially a concern in low-middle-income countries. However, health and medically-related reforms are being actively implemented in some middle-income countries like India. Identifying low birth weight (LBW) babies with their determinants across the whole country is essential to formulate regional and area-specific interventions. The objective of this study was to find out the burden and determinants of LBW on the regional and residential (rural-urban) divisions of India. The present study was based on the NFHS-5 dataset (2019-21), a nationally representative survey in India. A total of 209,223 births were included in this study. A newborn weighing less than 2500 g was considered as LBW. According to the objectives, we used frequency distribution, chi-square test and binary logistic regression analysis for analysing the data. About 18.24% of the babies were LBW in India, significantly higher in rural areas than in urban areas (18.58% vs 17.36%). Regionally prevalence was more frequent in western (20.63%) and central (20.16%) rural areas. Regarding maternal concerns, in the eastern and southern regions of India, mothers aged 25-34 were less likely to have LBW children than mothers aged 35-49 years. It was found that the risk of LBW was more likely among the children born out of unintended pregnancies in almost all regions except for eastern part. In rural India, women who delivered children at home were more likely to have LBW children in India (AOR = 1.19, CI: 1.12-1.28, p < 0.001) and its central, northern, and southern regions than those who gave birth in institutions. The study indicates that LBW coexists with lower maternal education levels and poor household wealth index across all regions. About 58% and 57% of cumulative effects of independent variables on LBW can be distinguished in urban and rural India, respectively. Targeted-specific strategies need to be undertaken as per region and geographical variations. Then only India should be able to decline LBW as proposed by National Health Policy.


Allosteric Regulation of 3CL Protease of SARS-CoV-2 and SARS-CoV Observed in the Crystal Structure Ensemble.
The 3C-like protease (3CLpro) of SARS-CoV-2 is a potential therapeutic target for COVID-19. Importantly, it has an abundance of structural information solved as a complex with various drug candidate compounds. Collecting these crystal structures (83 Protein Data Bank (PDB) entries) together with those of the highly homologous 3CLpro of SARS-CoV (101 PDB entries), we constructed the crystal structure ensemble of 3CLpro to analyze the dynamic regulation of its catalytic function. The structural dynamics of the 3CLpro dimer observed in the ensemble were characterized by the motions of four separate loops (the C-loop, E-loop, H-loop, and Linker) and the C-terminal domain III on the rigid core of the chymotrypsin fold. Among the four moving loops, the C-loop (also known as the oxyanion binding loop) causes the order (active)-disorder (collapsed) transition, which is regulated cooperatively by five hydrogen bonds made with the surrounding residues. The C-loop, E-loop, and Linker constitute the major ligand binding sites, which consist of a limited variety of binding residues including the substrate binding subsites. Ligand binding causes a ligand size dependent conformational change to the E-loop and Linker, which further stabilize the C-loop via the hydrogen bond between the C-loop and E-loop. The T285A mutation from SARS-CoV 3CLpro to SARS-CoV-2 3CLpro significantly closes the interface of the domain III dimer and allosterically stabilizes the active conformation of the C-loop via hydrogen bonds with Ser1 and Gly2; thus, SARS-CoV-2 3CLpro seems to have increased activity relative to that of SARS-CoV 3CLpro.


Endoscopic Endonasal Management of Craniopharyngioma.
Craniopharyngioma is a rare clinical entity that poses a significant management challenge given their location and propensity to recur. As part of a minimally disruptive treatment paradigm, the expanded endonasal approach has the potential to improve rates of resection, improve postoperative visual recovery, and minimize surgical morbidity. This article updates the otolaryngologic community on the basic principles and techniques regarding the incorporation of the endoscopic, endonasal approach in the management paradigm of craniopharyngioma.


A study of degradation behaviour and biocompatibility of Zn-Fe alloy prepared by electrodeposition.
Zinc is a biodegradable metal, which exhibits more moderate biodegradability than magnesium and iron, so that it has great application potential in the field of biomedical materials. Alloying of zinc and iron may lead to producing a new type of implant material Zn-Fe alloy, which might be able to meet the requirements for a moderate degradation rate. However, due to the huge difference in the melting point between zinc and iron, the preparation of Zn-Fe alloy is quite challenging and hence rarely reported. In this study, we show that Zn-Fe alloys can be successfully prepared by electrodeposition technology. The microstructures, composition, degradation properties and biocompatibility of the Zn-Fe alloys were systematically studied. The results showed that the content of iron in the alloys ranged from 0 to 8 wt%, depending on the concentration of Fe ions and the current density. In the alloys, the major's phases were η, δ and Г1, and they were mainly affected by the ion concentration in the electrolyte. In the in vitro immersion tests, the Zn-Fe alloy ZF2-1 showed the highest immersion corrosion rate, while ZF3-1 showed the highest electrochemical corrosion rate. Moreover, we found that the corrosion rates of the alloys were significantly higher than that of the pure Fe. In the in vivo experiments, we confirmed that the Zn-Fe alloy possessed good biocompatibility. These results demonstrate that the electrodeposition technology is a good method to prepare Zn-Fe alloys, and the Zn-Fe alloys prepared by this method are potentially promising materials for biomedical applications.


Risk factors for recurrent falls in older adults: A systematic review with meta-analysis.
Older adults who fall recurrently (i.e., 2 or more falls/year) are at risk of functional decline and mortality. Understanding which risk factors for recurrent falls are most important will inform secondary fall prevention strategies that can reduce recurrent falls risk. Thus, we conducted a systematic review with meta-analysis to determine the relative risk of recurrent falls for different types of falls risk factors. MEDLINE, EMBASE, PsycINFO, and CINAHL databases were searched on April 25, 2019 (Prospero Registration: CRD42019118888). We included peer-reviewed prospective studies which examined risk factors that contributed to recurrent falls in adults aged ≥ 60 years. Using the falls risk classification system of Lord and colleagues, we classified each risk factor into one of the following domains: 1) balance and mobility; 2) environmental; 3) psychological; 4) medical; 5) medication; 6) sensory and neuromuscular; or 7) sociodemographic. We calculated the summary relative risk (RR) for each domain and evaluated the risk of bias and quality of reporting. Twenty-two studies were included in this systematic review and meta-analysis. Four domains predicted recurrent falls: balance and mobility (RR:1.32;95 % CI:[1.10, 1.59]), medication (RR:1.53;95 % CI:[1.11, 2.10]), psychological (RR:1.35;95 % CI:[1.03, 1.78]), and sensory and neuromuscular (RR:1.51;95 % CI:[1.18, 1.92]). Each of these four domains can be viewed as a marker of frailty. The risk of bias was low, and the study quality was high (minimum:19/22). Older adults with markers of frailty are up to 53 % more likely to experience recurrent falls. Strategies that identify and resolve frailty markers should be a frontline approach to preventing recurrent falls.


Insulin elevates hippocampal GABA levels during ischemia. This is independent of its hypoglycemic effect.
There are reports that insulin may protect neurons from the effects of ischemia. The mechanisms for this protection are not fully understood. We studied the extracellular levels of glutamate and GABA in insulin-treated animals exposed to transient forebrain ischemia under normoglycemic and hypoglycemic conditions. In vivo microdialysis technique was used to collect extracellular fluid from the CA1 region of the hippocampus. There was a significant increase in GABA levels in the two insulin-treated sub-groups compared with the controls. GABA levels were < 1 pmol/10 microliters in three 10 min collections prior to ischemia in all the groups. It increased from 11.1 +/- 3.5 pmol/10 microliters in the conrol group to 47 +/- 5 (P < 0.001) in the insulin-treated hypoglycemic group and up to 47.2 +/- 9.3+ (P < 0.005) in the insulin-treated normoglycemic group (two-way ANOVA with repeated measures). Ischemia resulted in an increase in the glutamate levels. The glutamate levels returned to baseline within 30 min of the insult. There were no significant differences in the glutamate levels in three groups. The increase in GABA concentrations in the extracellular space may result in the inhibition of CA1 pyramidal neurons. This may be a possible mechanism of neuronal protection in animals treated with insulin (with or without being hypoglycemic) during ischemia.


COVID-19 and eating disorders during confinement: Analysis of factors associated with resilience and aggravation of symptoms.
To assess the level of deterioration in functioning of ED patients during confinement, due to COVID-19, and examine potential contributing factors (coping strategies, anxiety-depressive symptomatology and personality traits). A total of 74 ED patients in treatment before the COVID-19 outbreak, contributed to this study. Baseline pre-treatment evaluation included the SCL-90R, TCI-R, EDI-2 and Y-FAS 2.0 questionnaires for general psychopathology, personality and ED severity indexes. ED symptoms, coping strategies, socio-demographic data and COVID-19 concerns were collected by clinicians through a semi-structured telephone survey during lockdown. A deterioration in ED symptoms and general psychopathology (anxiety and depression), during lockdown, was associated with low self-directedness. Higher ED symptomatology during confinement was associated with less-adaptive coping strategies to deal with lockdown situation leading to an increase in weight. These specific vulnerability factors to further confinement or stressful situations may help design personalized preventive and therapeutic approaches.


Microscopic extracapsular extension in the axilla: is this an indication for axillary radiotherapy?
Although the axilla is often treated with radiotherapy (RT) postoperatively when microscopic extracapsular extension (ECE) of lymph nodal metastases is present, little data are available to assess axillary failure in the absence of such treatment. As it has been the practice at this institution to withhold axillary irradiation in the presence of microscopic extracapsular spread, we retrospectively analyzed our results for axillary recurrence, disease-free survival (DFS), and overall survival (OS). Clinical records were reviewed of 82 women with Stage II node positive breast cancer treated with lumpectomy, axillary dissection, and RT in addition to systemic chemo/hormonal therapy. Axillary surgery consisted of a level I, II, +/- III dissection, with a median of 16.5 nodes removed. Tangential radiotherapy fields were used to treat the breast. All patients were also treated with an abbreviated supraclavicular field with the lateral border medial to the humeral head. Pathological sections were available for review in 72 of the 82 women. Twenty-seven of 72 (37.5%) had evidence of ECE; 45 of 72 (62.5%) had metastatic carcinoma confined within the nodal capsule. Clinical characteristics were comparable between the patients with and without ECE with the exception of (a) pathologic subtype, with a greater percentage of infiltrating ductal tumors associated with ECE (p = 0.044), and (b) number of positive lymph nodes, with 93% of patients without ECE having one to three positive nodes vs. only 56% among patients with ECE (p < 0.001). With a median follow-up of 40 months, 1 of 27 patients (4%) with ECE experienced an axillary failure as a component of first failure compared to 0 of 45 patients without ECE (p = 0.4). There were no isolated axillary failures. Five-year disease-free survival (72% without ECE vs. 57% with ECE, p = 0.12) and overall survival (83% vs. 53%, respectively, p = 0.068) suggested a less favorable outcome for patients with ECE. Microscopic ECE appears to be associated with increased axillary involvement and decreased survival rather than subsequent axillary failure. Our data suggest that radiotherapy to a dissected axilla may be omitted for the sole indication of microscopic extracapsular disease.


Occupational exposure to petroleum products and respiratory health: a cross-sectional study from Algeria.
To investigate the possible impact of long-term occupational exposure to hydrocarbons on respiratory health. Respiratory health was assessed by questionnaires, spirometry, and exhaled nitric oxide in 250 male workers from a company handling and distributing refined petroleum products (exposed) and 250 electricians (controls). Exposure to hydrocarbons was assessed by personal air monitoring. Aerial exposure to hydrocarbons was low. Respiratory and nasal symptoms were significantly more frequent among exposed subjects than among controls. Although forced vital capacity and forced expiratory volume in 1 second did not differ, ratio of forced expiratory volume in 1 second to forced vital capacity and maximal expiratory flows were significantly lower in exposed than in control subjects, adjusting for smoking. Exhaled nitric oxide was significantly higher among exposed subjects (30.1 ppb) than among controls (21.6 ppb), adjusting for age and smoking. Even low exposure to petroleum-derived hydrocarbons is associated with more respiratory and nasal symptoms, lower pulmonary function, and airway inflammation.


Cryptic and abundant marine viruses at the evolutionary origins of Earth's RNA virome.
Whereas DNA viruses are known to be abundant, diverse, and commonly key ecosystem players, RNA viruses are insufficiently studied outside disease settings. In this study, we analyzed ≈28 terabases of Global Ocean RNA sequences to expand Earth's RNA virus catalogs and their taxonomy, investigate their evolutionary origins, and assess their marine biogeography from pole to pole. Using new approaches to optimize discovery and classification, we identified RNA viruses that necessitate substantive revisions of taxonomy (doubling phyla and adding >50% new classes) and evolutionary understanding. "Species"-rank abundance determination revealed that viruses of the new phyla "Taraviricota," a missing link in early RNA virus evolution, and "Arctiviricota" are widespread and dominant in the oceans. These efforts provide foundational knowledge critical to integrating RNA viruses into ecological and epidemiological models.


Protection of the brain during hypothermic perfusion.
The adequacy of the circuits for brain perfusion has been explored by hemodynamic assessment using the ability of the brain to autoregulate blood flow as an indicator, and by morphologic observation using carbon black or Evans blue infusion into the brain perfused antegradely or retrogradely. It is concluded that the safe pressure of cerebral perfusion needed to maintain cerebral integrity is between 40 and 50 mm Hg in both normothermic and hypothermic perfusions, a pressure that can be generated by nonpulsatile pump flows through the pump greater than 40 mL.kg-1 x min-1. Morphologic studies revealed development of focal infarctions in the brain and destruction of the blood-brain barrier by retrograde cerebral perfusion. The retrograde approach, therefore, is definitely inferior to the antegrade method. Antegrade perfusion for 90 minutes, however, produced minimal cerebral edema, suggesting the need for further improvement even in techniques of antegrade perfusion.


Neurophysiological follow-up in a case of chronic progressive epilepsia partialis continua of childhood.
We report the waking and sleeping polygraphic and evoked potential data recorded during the follow-up of a child with chronic progressive epilepsia partialis continua of childhood (Bancaud's type II). The findings that emerged from these investigations coupled with the clinical pattern enabled us to delineate the course of this rare condition and provided clues for a tentative interpretation of the pathogenesis of the repetitive myoclonic jerks typical of epilepsia partialis continua, on which there is as yet no consensus. In our case involvement of cortico-subcortical systems seems probable.


Low plasma levels of hCG after 10,000-IU hCG injection do not reduce the number or maturation of oocytes recovered in patients undergoing assisted reproduction.
Our purpose was to determine whether there is a correlation between human chorionic gonadotropin (hCG) blood levels and oocyte maturation. Three samples of blood were obtained at different times from hCG administration as follows: 12 hr, 36 hr, during oocyte recovery, and at 84 hr, when the patient comes for embryo transfer. A total of 5036 oocytes was retrieved from 404 patients prospectively recruited between April 1996 and March 1997. The percentage of metaphase-II oocytes at different blood levels ranged from 84 to 88%. The general trend does not show any significant increase in percentage of metaphase-II oocytes in association with an increasing serum hCG concentration. The results of this study suggest that at 12, 36, and 84 hr after hCG administration, levels as low as 50, 45, and 9 IU/L of hCG, respectively, are equally potent as higher levels at initiating maximal oocyte maturity.


Attention-deficit hyperactivity disorder in adults.
Attention-deficit hyperactivity disorder (ADHD) is probably the most common chronic undiagnosed psychiatric disorder in adults. It is characterized by inattention and distractibility, restlessness, labile mood, quick temper, overactivity, disorganization, and impulsivity. It is always preceded by the childhood diagnosis, a disorder that is rarely inquired about, and usually overlooked. Treatment can be dramatically effective. Approximately two thirds of adult ADHD patients experience moderate-to-marked improvement with psychoeducational management and stimulant drug therapy.


Use of problem based learning activity to improve attitudes regarding inter-professional collaborative teamwork in mental health nursing students: An evaluation study.
Inter-professional collaboration results in improved processes, quality, cost-effectiveness, and outcomes in health care. Despite benefits of collaboration, little is known about effective nursing education approaches in collaboration. A pre-test, post-test brief longitudinal educational evaluation design was implemented utilizing a teamwork attitudes questionnaire to explore thirty-six Midwestern United States undergraduate nursing students' attitudes about collaborative care. An electronic educational module about collaborative nursing practice was used. Also, participants developed visual representations (maps) of collaborative care teams utilizing reverse case-study approach. The TAQ tool demonstrated significantly improved students' valuation of teamwork after the electronic module activity (t = 5.976, p = 0.000) and increased the identification of need for administrative support for effective teamwork (t = 33.53, 0.000). Collaborative team map drawings demonstrated that patient's frequently fail to identify themselves (75%) and social workers (70%) as part of their care team. Patients (58.3%) and students (77.8%) however, frequently identified family members as important to care. Further study should identify how nurses can fully engage and sustain involvement of family members and social workers in collaborative mental health care. Benefit in student nurses' attitudes about teamwork was found after a brief educational learning module about collaboration.


Electrical ablation of atrial muscle. II. Early and late electrophysiologic observations in canine atria.
Electrical ablation techniques (ECT) have had limited success in achieving control of arrhythmias originating in the right atrial free wall (RAFW). To ascertain determinants for successful ECT, we studied the clinical and cellular electrophysiologic effects of electrical ablation of the RAFW. After performing electrical ablation of the RAFW in 12 beagle puppies, the following studies were performed: Holter monitoring first 24 hours (eight puppies), and 11 weeks later (four puppies); clinical electrophysiologic study (four puppies); and microelectrode study (ME) (eight puppies). Arrhythmias (AR) and conduction disturbances (CD) frequently occurred immediately following ECT: ventricular tachycardia (VT) (seven puppies), junctional tachycardia (one puppy), and asystole or complete AV block (AVB) (four puppies). Holter monitoring during the first 24 hours after ECT revealed VT (four puppies), frequent ventricular premature depolarizations (one puppy), and type 2 second-degree AVB (four puppies). AR were rarely seen late after ECT. During clinical EP study 11 weeks after ablation, atrial fibrillation was induced in three of four puppies; none had AR prior to ECT. Early ME study revealed a nonhomogeneous atrial infarct--a central zone of "dead" cells surrounded by peripheral islands of depressed cellular activity. Cells with normal action potential characteristics were noted in between. We conclude that Electrical ablation of the RAFW is associated with a high incidence of early AR and CD. Because of the nonhomogeneous nature of tissue injury produced during ECT, careful atrial mapping is critically important. Local regions of conduction delay and block may provide a substrate for the late development of atrial arrhythmias.


Experimental acute right ventricular failure and right ventricular assist in the dog.
We describe a technique for the production of acute progressive right ventricular failure in experimental animals that mimics the hemodynamic characteristics of right ventricular failure found in some patients being weaned from extracorporeal circulation after surgical repair of left ventricular abnormalities. The technique combines three alterations of right ventricular state: excision of the tricuspid valve, ventriculotomy, and ligation of the right coronary artery. Seven control dogs died within 3 hours after this intervention. Death was due to low cardiac output as a result of low left atrial and pulmonary arterial pressures. Right atrial pressure was high. Use of a right ventricular assist device in an additional seven dogs to pump blood from the right atrium to the pulmonary artery confirmed good preservation of left ventricular function by reestablishing adequate left ventricular filling pressure. All seven dogs survived for more than 3 hours. The validity of the technique in restricting failure principally to the right ventricle was thus demonstrated.


Determination of critical micelle concentrations and aggregation numbers by fluorescence correlation spectroscopy: aggregation of a lipopolysaccharide.
Fluorescence correlation spectroscopy (FCS) is often used to determine the mass or radius of a particle by using the dependence of the diffusion coefficient on the mass and shape. In this article we discuss how the particle size of aggregates can be measured by using the concentration dependence of the amplitude of the autocorrelation function (ACF) instead of the temporal decay. We titrate a solution of aggregates or micelles with a fluorescent label that possesses a high affinity for these structures and measure the changes in the amplitude of the ACF. We develop the theory describing the change of the ACF amplitude with increasing concentrations of labels and use it to fit experimental data. It is shown how this method can determine the aggregation number and critical micelle concentration of a standard detergent nonaethylene glycol monododecyl ether (C12E9) and a lipopolysaccharide (LPS: Escherichia coli 0111:B4).


Transcriptional profiles from patients with dystrophinopathies and limb girdle muscular dystrophies as determined by qRT-PCR.
Mutations in genes coding for the dystrophin-glycoprotein complex (DGC) cause inherited muscular dystrophies (MD), including Morbus Duchenne (DMD) and M. Becker (BMB) as well as limb-girdle muscular dystrophies (LGMD). New insights into the pathophysiology of the dystrophic muscle, the identification of compensatory mechanisms and additional proteins interacting with dystrophin are essential for developing new treatments. In order to define molecular mechanisms induced by lack of dystrophin and the subsequent counter-regulatory transcriptional response of degenerating muscle fibres, we have investigated the mRNA expression of 19 functionally linked genes in biopsies of patients with MD by means of real time qRT-PCR. Our results define a uniform transcriptional profile of the dystrophic muscle characterized by degeneration and regeneration. Several genes encoding structural proteins appear remarkably highly expressed.


23Na NMR study of intracellular sodium ions in Dictyostelium discoideum amoeba.
The intracellular sodium concentration in the amoebae from the slime mold Dictyostelium discoideum has been studied using 23Na NMR. The 23Na resonances from intracellular and extracellular compartments could be observed separately in the presence of the anionic shift reagent Dy(PPPi)7-2 which does not enter into the amoebae and thus selectively affects Na+ in the extracellular space. 31P NMR was used to control the absence of cellular toxicity of the shift reagent. The intracellular Na+ content was calculated by comparison of the intensities of the two distinct peaks arising from the intra- and extracellular spaces. It remained low (0.6 to 3 mM) in the presence of external Na+ (20 to 70 mM), and a large Na+ gradient (20- to 40-fold) was maintained. A rapid reloading of cells previously depleted of Na+ was readily measured by 23Na NMR. Nystatin, an antibiotic known to perturb the ion permeability of membranes, increased the intracellular Na+ concentration. The time dependence of the 23Na and 31P NMR spectra showed a rapid degradation of Dy(PPPi)7-2 which may be catalyzed by an acid phosphatase.


Exposure to Organochlorine Pesticides and Female Breast Cancer Risk According to Molecular Receptors Expression: a Systematic Review and Meta-analysis of Epidemiological Evidence.
Organochlorine pesticides (OCP) have been proposed as potential mammary carcinogens since they interact with steroid signaling pathways. However, the epidemiological results are not conclusive. Most studies have evaluated breast cancer (BC) as a single entity without considering the different molecular expressions, including estrogen receptor (ER), progesterone receptor (PR), and HER2, that could differ in their association with these contaminants. Hence, we assessed the association between biological concentration of OCP and BC, according to its molecular receptor expression, based on a systematic review and meta-analysis. Of the 141 articles eligible for full-text review, nine met the inclusion criteria. The way in which molecular expression was reported was heterogeneous; therefore, the inclusion of studies in the meta-analysis was limited to eight articles. A negative association was identified for β-hexachlorocyclohexane and trans-nonachlor with ER + tumors and between hexachlorobenzene and ER - tumors. No associations were observed for p,p'-dichlorodiphenyldichloroethylene, cis-nonachlor, and dieldrin, and it was not possible to evaluate the associations between OCP with HER2 expression or triple-negative tumors due to lack of data. The results suggest that some OCP might be associated with BC depending on the expression of ER. However, the evidence is not conclusive due to the scarce data. We identified several methodological aspects to fill the gaps in knowledge and increase the comparability among studies.


Early complications after percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1,843 ablations in 1,211 patients in a single centre: experience over 10 years.
To evaluate the incidence of adverse events and associated factors after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma within 30 days. The early complications that occurred within 30 days after RFA at a single institution from January 2000 to July 2010 were reviewed in order to evaluate the morbidity, mortality, and risk factors associated with the complications. In total, 1,211 patients (845 men, 70.5%) with a mean age of 68 years (range, 27-88 years) underwent 1,843 RFA procedures. The overall incidence rate of complications was 6.8% (125 cases). Major complications (n=36, 2%) included liver abscess (n=15, 0.8%), intraperitoneal bleeding (n=8, 0.4%), liver failure (n=5, 0.3%), variceal bleeding (n=3, 0.2%), haemothorax (n=2, 0.1%), cholecystitis (n=2, 0.1%), and bowel perforation (n=1, 0.1%). Among the minor complications (n=89, 4.8%), the most common was the post RFA syndrome accompanied by pain and fever (n=75, 4.1%). Other minor complications included significant pleural effusion (n=7, 0.4%), skin wound infection (n=4, 0.2%), and thermal injuries to the skin (n=3, 0.2%). Procedural infections significantly increased with tumour size (OR=1.379; 95% confidence interval [CI], 1.191-1.579; p<0.001), and multiple overlapping ablations (OR=1.118; 95% CI, 1.019-1.227, p=0.018). Thrombocytopenia (<50,000/μl), prothrombin time, and serum albumin level were significantly associated with post-RFA bleeding episodes (p=0.041, p=0.021, and p=0.003, respectively). The overall mortality rate was 0.3% (three cases of hepatic failure, two case of sepsis, and one case of renal failure). RFA is a safe and effective local treatment for hepatocellular carcinoma. Careful selection of patients and appropriate RFA planning could decrease procedural mortality and morbidity.


Relation between renal and hepatic excretion of drugs. V. Factors influencing accumulation of phenol red in kidney and liver tissues from rats of different ages.
Following bile duct ligation (DL) or bilateral nephrectomy (NX), phenol red accumulation in kidney or liver tissue, respectively, is reduced in rats of different ages. This is in contrast to in vivo experiments showing a compensatory increase of renal or hepatic excretion of phenol red in adult rats after DL or NX, respectively. The present study was performed to clarify this discrepancy. Three possible reasons were taken into consideration: 1. competition between accumulation of phenol red and bilirubin or bile acids; 2. influence of humoral factors occurring in serum of DL-rats on accumulation capacity; 3. changes of phenol red binding in homogenate of the kidney cortex or liver tissue after DL or NX. Ad 1. There exist inhibitory effects of bilirubin and cholic acid on phenol red accumulation. This inhibition is a competitive as well as a toxic one, apparently caused by a reduction of intracellular phenol red binding. Similar results have been obtained in in vivo experiments. During continuous infusion of bilirubin both renal and hepatic excretion of phenol red is significantly diminished. Ad 2. Incubation of tissue slices of control animals in serum of DL-rats does not indicate the existence of humoral factors reducing accumulation of phenol red after DL. Only in adult rats the plasma protein binding of phenol red is reduced after DL; in 10-day-old rats the binding capacity of the proteins for the dye is unchanged after DL. Ad 3. In young animals the phenol red binding on tissue homogenate is significantly reduced after DL or NX in kidney or liver; binding capacity of adult rats' tissue homogenate is unchanged after both operations. It can be concluded that renal and hepatic excretion capacity cannot be increased within a few hours after these blocking operations and obviously a functional reserve of the transport mechanisms does not exist.


The importance of eosinophil cells in kidney allograft rejection.
The composition of the intragraft cellular infiltrate was studied in 83 renal allograft recipients with the technique of fine-needle aspiration cytology in the first four weeks following kidney transplantation. We found a significantly (P less than 0.05) higher mean tissue eosinophil percentage in patients who had irreversible rejections with transplant loss than in those who had reversible rejections (12.54 +/- 2.31 versus 3.79 +/- 1.14, mean +/- SEM). Patients who had serious, dialysis-requiring rejections also showed a significantly (P less than 0.05) higher mean tissue eosinophil percentage than those who had reversible rejections (21.40 +/- 5.98 versus 3.79 +/- 1.14, mean +/- SEM). The frequency of the HLA B8 antigen was 46.2% in patients who had excessive tissue eosinophilia, whereas its frequency in all the studied patients was 18.3%. Based on our observations, the presence of more than 4% eosinophils in the tissue inflammatory exudate is a specific (91%) and fairly sensitive (78%) indicator of irreversible and severe acute rejections.