The origin of the reticulo-olivary projection in the rat: a retrograde horseradish peroxidase study.
Electrophoretic injections of horseradish peroxidase were made in different parts of the rat inferior olivary complex using a ventral approach. Data from these injections provide anatomical evidence for the existence of a projection to the inferior olive which takes origin from reticular nuclei in the brainstem. The majority of reticulo-olivary neurons are located in the nucleus raphe obscurus and nucleus raphe pallidus. Other reticular nuclei which contribute to this projection include the nucleus reticularis ventralis and nucleus reticularis gigantocellularis. Analysis of injections confined to specific parts of the olivary complex reveals a topographical pattern in the reticulo-olivary projection. Caudal parts of the complex receive input primarily from the nucleus reticularis ventralis. As more rostral and medial parts of the inferior olive are included in the injection, there is concomitant shifting of labeled neurons to the nucleus reticularis gigantocellularis and the raphe nuclei. The reticulo-olivary neurons may serve several non-mutually exclusive roles in olivary circuitry. They may be the source of serotonin and/or substance P to the nucleus. Physiologically, they may provide the inhibitory input observed in the nucleus. Finally, some of these neurons may be the brainstem relay of the lateral funiculus and dorsolateral funiculus spino-olivo-cerebellar pathway proposed by Larson and his co-workers (J. Physiol., Lond. 203, 611-640, 641-649).


Photoactivatable HNO-releasing compounds using the retro-Diels-Alder reaction.
We synthesized hetero-Diels-Alder cycloadducts from acyl nitroso derivatives and 9,10-dimethylanthracene, to be photo-inducible HNO-releasing agents and found that introduction of conjugated nitroaromatic groups effectively enhanced the responsiveness of HNO release to UV-A irradiation; we confirmed photoinduced HNO formation by EPR and GCMS analysis.


Contemporary demographics and complications of patients treated for open ankle fractures.
Open ankle fractures are rare injuries with a high likelihood of wound complications and subsequent infections. There is limited information about the complications and outcomes of these injuries in different age groups. The aim of this study was to assess the contemporary demographics and complications related to this injury. We performed a chart review of all the 3030 patients treated for ankle fractures at a Level 1 trauma centre from 2006 to 2011. 137 (4.5%) patients had an open ankle fracture. The demographic data, injury mechanism, comorbidities, and fracture type were collected. Treatment, complications, length of stay and number of outpatient visits were also recorded. The mean age of the patients was 60 years and 56% were women. Most fractures were Weber type B with a medial sided wound (93%). Only 20% of the fractures were the result of high-energy trauma, and 31% were Gustilo grade III injuries. Immediate internal fixation was performed in 82% of patients, and the wound was primarily closed in most cases (80%). The incidence of postoperative wound necrosis and deep infection was 18% and 17%, respectively. There were more deep infections if pulsatile lavage was used during the wound debridement (p=0.029). About 14 (10%) patients required a flap reconstruction to cover the soft-tissue defect. Every other patient (54%) had a complication, and 21 patients (15%) suffered a long-term disability related to the injury. The number complications did not differ for nighttime and daytime operations (p=0.083). High-energy injuries were more common in younger patients (p<0.001) and these patients also had more lateral sided open wounds than older patients (p=0.002). Interestingly, younger patients also had significantly more complications (p=0.024), suffered more often from chronic pain (p=0.003), and required more flap reconstructions (p=0.026), reoperations (p=0.026), and outpatient clinic visits (p=0.006). Open ankle fractures have a high complication rate and often require multiple surgical procedures. In young patients these injuries are more likely to be the consequence of high-energy trauma leading to more complications and subsequently increased healthcare resource utilisation.


Building A Strong and Inclusive Workforce for Health: In Conversation with North Carolina Commerce Secretary Machelle Baker Sanders and Health Secretary Kody Kinsley.
North Carolina faces a significant health workforce shortage exacerbated by the COVID-19 pandemic. To meet this challenge, the Department of Commerce and the Department of Health and Human Services are prioritizing equity, creativity, and collaboration.


FlavoDb: a web-based chemical repository of flavonoid compounds.
There are many online resources that focus on chemical diversity of natural compounds, but only handful of resources exist that focus solely on flavonoid compounds and integrate structural and functional properties; however, extensive collated flavonoid literature is still unavailable to scientific community. Here we present an open access database 'FlavoDb' that is focused on providing physicochemical properties as well as topological descriptors that can be effectively implemented in deducing large scale quantitative structure property models of flavonoid compounds. In the current version of database, we present data on 1, 19,400 flavonoid compounds, thereby covering most of the known structural space of flavonoid class of compounds. Moreover, effective structure searching tool presented here is expected to provide an interactive and easy-to-use tool for obtaining flavonoid-based literature and allied information. Data from FlavoDb can be freely accessed via its intuitive graphical user interface made available at following web address: http://bioinfo.net.in/flavodb/home.html.


Effect of evaporation-induced osmotic changes in culture media in a dry-type incubator on clinical outcomes in in vitro fertilization-embryo transfer cycles.
This study investigated whether adding outer-well medium to inhibit osmotic changes in culture media in a dry-type incubator improved the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) cycles. In culture dishes, the osmotic changes in media (20 µL)-covered oil with or without outer-well medium (humid or dry culture conditions, respectively) were compared after 3 days of incubation in a dry-type incubator. One-step (Origio) and G1/G2 (Vitrolife) media were used. The osmotic changes in the dry culture condition (308 mOsm) were higher than in the humid culture conditions (285-290 mOsm) after 3 days of incubation. In day 3 IVF-ET cycles, although the pregnancy rate did not significantly differ between the dry (46.2%) and humid culture (52.2%) groups, the rates of abortion and ongoing pregnancy were significantly better in the humid culture group (2.3% and 50.2%, respectively) than in the dry culture group (8.3% and 37.8%, respectively, p<0.05). In day 5 IVF-ET cycles, the abortion rate was significantly lower in the humid culture group (2.2%) than in the dry culture group (25.0%, p<0.01), but no statistically significant difference was observed in the rates of clinical and ongoing pregnancy between the dry (50.0% and 25.0%, respectively) and humid culture groups (59.5% and 57.3%, respectively) because of the small number of cycles. Hyperosmotic changes in media occurred in a dry-type incubator by evaporation, although the medium was covered with oil. These osmotic changes were efficiently inhibited by supplementation of outer-well medium, which resulted in improved pregnancy outcomes.


Underlying causes of cocaine, amphetamine and opioid related deaths in Australia.
To examine the characteristics of deaths in Australia where opioids, cocaine or amphetamines were mentioned, taking into account changes in the use and availability of these drugs in recent years. Data were analysed from the Australian Bureau of Statistics and Causes of Death dataset between 1997 and 2002 on all deaths in which cocaine, amphetamines or opioids were mentioned including deaths where (a) the drugs were considered an underlying cause of death, (b) the drugs contributed to accidental drug-induced death, and (c) deaths primarily due to other causes. Data from the Australian National Drug Strategy Household Survey were also used to examine the prevalence of use of amphetamines, cocaine and opioids in Australia. Thirteen deaths were attributed primarily to cocaine, 68 to amphetamines, and 4591 to opioids. An increase occurred in mentions of amphetamines, but half of these were primarily attributed to opioids. Opioid related deaths declined dramatically in 2001, consistent with a marked reduction in availability of heroin in Australia. Cocaine mentions remained relatively stable, with most cases primarily attributed to opioids. Of the other underlying causes of death, suicide was the most prevalent underlying factor, particularly for amphetamine and opioid related deaths. Compared with opioid-related deaths, there are small numbers of deaths related to psychostimulants in Australia. Accidental drug induced deaths account for the majority of deaths in which these drugs are mentioned, although minorities of drug related deaths are attributed to suicide.


[Posterior retinal hole secondary to a candida retinitis].
We describe the case of a 36-year-old man with a history of intravenous heroin use, who was HIV negative. Left ocular examination disclosed a focal candida retinitis in the posterior pole associated with vitritis and moderate iritis. Treatment with fluconazole inactived the chorio-retinal lesion and resolved the vitritis, but developed an inner limiting membrane contraction over the macula. Two years later, vitreous traction produced a retinal hole that needed argon laser photocoagulation. Candida retinitis which penetrates into the vitreous cavity can produce retinal holes by vitreous traction over the lesion.


Engaging with the Richmond Community to Reduce Pediatric Asthma Disparities: Findings from a Community-engaged Needs Assessment.
Childhood asthma disparities persist, with children living in low-income areas experiencing worse morbidity. We partnered with a community-academic research team and stakeholders to conduct a needs assessment to understand barriers and supports to asthma treatment. We convened a community advisory board, comprised of parents of children with asthma, youth with asthma, and members of key community organizations. Two focus groups with parents of children with asthma and four focus groups with youth with asthma were conducted, and a survey was administered to 100 parents. A visual mapping process was used to gather qualitative data about barriers, strategies, and outcomes, and allowed advisory board members to interpret focus group and survey data within the lived experiences of families. Focus group themes included parent stress/anxiety, concerns about school nurses, and lack of trust in providers. Findings from focus groups and surveys suggested that emergency department visits were not perceived negatively by families, although health providers and researchers generally view them as such. Public health implications include systemic changes that allow the healthcare system to address families' acute needs and worry. A community program focused on education and coordination among families, schools, and medical homes might improve asthma outcomes at the population level.


Exploring the complex role of gut microbiome in the development of precision medicine strategies for targeting microbial imbalance-induced colon cancer.
The gut microbiome has been increasingly recognized as a key player in the development and progression of colon cancer. Alterations in the gut microbiota, known as dysbiosis, can lead to a variety of medical issues. Microbial adaptation through signals and small molecules can enhance pathogen colonization and modulate host immunity, significantly impacting disease progression. Quorum sensing peptides and molecules have been linked to the progression of colon cancer. Various interventions, such as fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics, have been used to reverse dysbiosis with mixed results and potential side effects. Thus, a personalized approach to treatment selection based on patient characteristics, such as individual gut microbiota manipulation, is necessary to prevent and treat diseases like colon cancer. With advances in metagenomic sequencing and other omics technologies, there has been a growing interest in developing precision medicine strategies for microbial imbalance-induced colon cancer. This review serves as a comprehensive synthesis of current knowledge on the gut microbiome involvement in colon cancer. By exploring the potential of utilizing the gut microbiome as a target for precision medicine, this review underscores the exciting opportunities that lie ahead. Although challenges exist, the integration of microbiome data into precision medicine approaches has the potential to revolutionize the management of colon cancer, providing patients with more personalized and effective treatment options.


Solar energy harnessing in hexagonally arranged Si nanowire arrays and effects of array symmetry on optical characteristics.
Investigation of solar energy harvesting in hexagonally arranged Si nanowire (NW) arrays is performed through optimizing the structural parameters, such as array periodicity (P), Si NW diameter (D) and length (L). The results demonstrate that there exist wide P and D/P 'windows' for the Si NW arrays, locating around 600 nm and 0.833 (i.e., D=500 nm), respectively, for achieving enhanced light absorption compared to their thin film counterparts with the same thickness, but with much less materials consumption. Calculation of the ultimate efficiency (UE) indicates that the light trapping capability is not monotonically increased with L, and that UE vibration is found when L is >1000 nm. Comparison of the light absorption spectra for hexagonally and squarely arranged Si NW arrays demonstrates that these two most widely employed array symmetries in practice have little impact on the light trapping capability.


Biomimetic mucin modified PLGA nanoparticles for enhanced blood compatibility.
Efforts to develop long circulating polymeric nanoparticles have propelled many strategies in nanoparticle surface modification to bypass immune surveillance and systemic clearance. In this context, our present study reports on the preparation and evaluation of mucin functionalized poly lactic-co-glycolic acid (PLGA) nanoparticles as hemocompatible, cell penetrating nanoparticulate drug delivery system. Amino groups of mucin were conjugated to the terminal carboxylic acid groups on PLGA to be followed by nanoparticle synthesis via standard solvent evaporation technique. Detailed in vitro experiments were performed to illustrate the significance of alternating copolymer structured mucin modified PLGA nanoparticles in terms of enhanced hemocompatibility and cellular uptake. Mucylation proved promising in controlling PLGA nanoparticle- interaction with plasma proteins (opsonins) and blood components via hemolysis, thrombogenecity and complement activation. Besides hemocompatibility, the modified and unmodified nanoparticles were also found to be cytocompatible with L929 and C6 cell lines. The fluorescent and confocal image analysis evaluated the extent of cellular uptake of nanoparticles into C6 cells. Specifically the combination of stealth properties and cellular internalization capacity of mucin modified PLGA nanoparticle (PLGA-Mucin) lead us to propose it as a safe, efficient and multifunctional nanoplatform for disease specific intravenous drug delivery applications as far as in vitro experiments are concerned.


Blood calprotectin in children with juvenile idiopathic arthritis: relationship to flare development after discontinuation of treatment.
The study aim was to prospectively evaluate the relationship between disease flare development in children with juvenile idiopathic arthritis (JIA) after discontinuation of treatment and serum calprotectin levels (MRP8/14). Determination of blood serum level of calprotectin was performed in 54 patients with inactive JIA from various regions of Ukraine. The inclusion criterion was the existence of an inactive state of the disease in children with JIA for at least 6 months. During 1 week after blood sampling for determination of serum calprotectin (MRP8/14) level the patients were completely discontinued of all therapy. Determination of calprotectin level in blood serum was performed with reagents EK-MRP8/14 Buhlmann (MRP8/14; S100A8/9), Switzerland, using the ELISA method. The trial results showed that 3 months after discontinuation of treatment in patients with inactive JIA, the flares developed in 5 out of 54 patients (9.3%). The median calprotectin level before discontinuation of the treatment was 1,700 ng/ml in patients who developed a flare, and 1,500 ng/ml in other studied patients (not statistically significant). At 6 months, the flare had developed in an additional 3 out of 48 (6.3%) of patients, who continued to be followed up, while their median calprotectin serum levels were 1,300 ng/ml and 1,500 ng/ml respectively (not statistically significant). At 12 months, the flares had developed in 13 more out of 45 (28.9%) patients, who continued to be followed up, while the median calprotectin serum level in these patients before discontinuation of treatment was 1,100 ng/ml and 1,650 ng/ml respectively (not statistically significant). After discontinuation of treatment a flare over the next year of follow-up developed in 38.9% of patients. The study results did not reveal a significant difference in calprotectin level in patients with JIA prior to complete discontinuation of treatment who developed a flare and those without a flare after 3, 6 and 12 months.


Juvenile Benign Diseases of the Breast.
The developmental phases of the breast are fluid and spread throughout prenatal, postnatal, and adolescent life. Developmental derangement during each phase can lead to disease formation. Before reaching adulthood, most abnormalities of the breast are benign in nature and can be characterized as congenital disorders, developmental disorders, or acquired disorders. Surgical intervention early in life is rarely warranted.


Possible Advantages Deriving from Patiromer Use in Hypertensive Patients Made Hyperkalemic by Renin-Angiotensin-Aldosterone Blocking Agents.
Hyperkalemia is an elevated level of serum potassium (K+) and does represent a life-threatening condition. In clinical practice, hyperkalemia mainly derives from an impaired renal K+ excretion which, in turn, is usually caused by either acute or chronic renal failure. In concordance with this, hyperkalemia is very common in several chronic conditions, such as kidney disease, diabetes mellitus, heart failure, hypertension, and coronary heart disease. In all of these conditions the use of Renin-Angiotensin-Aldosterone System inhibitors (RAASIs), such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonist is widely recommended and further increases the risk of hyperkalemia. As hypertension is concerned, clinical trials suggest that the risk of hyperkalemia associated with RAASIs ranges from 2 to 10%. This often leads to a reduction or complete cessation of RAASIs, leaving patients without protective medications. Patiromer, a new oral potassium-binding agent, has been approved for clinical use in several countries, including Europe and US. Clinical studies have demonstrated that patiromer is effective in inducing a rapid and sustained K+ reduction in various patient settings, including those where RAASIs are a fundamental component of cardiorenal protection. Patiromer is generally well tolerated and characterised by a good safety profile. Most importantly, patiromer use might allow the continuation of ACEIs and ARBs in hypertensive patients developing hyperkalemia during treatment and thereby favour a more effective and long-lasting cardiorenal protection.


Ethylene enhanced waterlogging tolerance by changing root architecture and inducing aerenchyma formation in maize seedlings.
Waterlogging negatively affects maize growth and yield. In this study, we found that ethylene played a vital role in plant adaptation to waterlogging. ET promotes better growth in seedlings under waterlogging conditions by altering root architecture and increasing lateral root formation by 42.1%. What's more, plants with high endogenous ethylene levels exhibited reduced sensitivity to waterlogging stress. ET also induced the formation of aerenchyma, a specialized tissue that facilitates gas exchange, in a different pattern compared to aerenchyma formed under waterlogging. Aerenchyma induced by ET was mainly located in the medial cortex of the roots and was not prone to decay. ethylene inhibited root elongation under normal conditions, but this inhibition was not alleviated under waterlogging stress. Upon activation of the ET signaling pathway, the transcription factor EREB90 promoted aerenchyma formation by enhancing the programmed cell death process. Overexpression of EREB90 resulted in increased waterlogging tolerance compared to wild type plants. Our findings suggest that pre-treatment of maize seedlings with ET before waterlogging stress can trigger the programmed cell death process and induce aerenchyma formation, thus improving waterlogging resistance.


A trans-national examination of the impact of the COVID-19 pandemic on abortion requests through a telemedicine service.
The COVID-19 pandemic is limiting access to reproductive healthcare worldwide. Substantial research gaps remain regarding the impact of the pandemic on access to abortion care. We performed a cohort analysis of abortion requests made through the telemedicine abortion service Women on Web (WoW) between 18 March 2020 and 4 May 2020. We used binary logistic regression analyses to test the association between COVID-19 as a reason for the help request and reporting having had an ultrasound to determine gestation and/or use of contraception. A subanalysis of Italy, Argentina, Malaysia and the United Arab Emirates (UAE) was executed to explore differences between countries. Of requests made during the study period, 43.5% (n=1972) were COVID-19-related. A negative association was found with having had an ultrasound to determine gestation length and COVID-19-related requests. Italy had the highest percentage (66.5%, n=117) of COVID-19-related requests in the subanalysis, followed by Argentina (55.3%, n=68), Malaysia (51.9%, n=41) and the UAE (44.4%, n=75). Almost half the women and pregnant people having an abortion through WoW reported experiencing obstacles to abortion care because of COVID-19. Abortion guidelines should be updated to permit abortion services via telemedicine. This is especially urgent during the ongoing pandemic.


Cardiologist concordance with the American College of Cardiology appropriate use criteria for cardiac testing in patients with coronary artery disease.
The American College of Cardiology Appropriate Use Criteria (AUC) were developed to guide use of myocardial perfusion single-photon emission computed tomography (MPS), stress echocardiography, and cardiac computed tomographic angiography (CCTA). To date, cardiologist application of AUC from a patient-based multiprocedure perspective has not been evaluated. A Web-based survey of 15 clinical vignettes spanning a wide spectrum of indications for MPS, STE, and CCTA in coronary artery disease was administered to cardiologists who rated the ordered test as appropriate, inappropriate, or uncertain by AUC application and suggested a preferred alternative imaging procedure, if any. In total 129 cardiologists responded to the survey (mean age 49.5 years, board certification for MPS 65%, echocardiography 39%, CCTA 32%). Cardiologists agreed with published AUC ratings 65% of the time, with differences in all categories (appropriate, 50% vs 53%; inappropriate, 42% vs 20%; uncertain, 9% vs 27%, p <0.0001 for all comparisons). Physician age, practice type, or board certification in MPS or echocardiography had no effect on concordance with AUC ratings, with slightly higher agreement for those board certified in CCTA (68% vs 64%, p = 0.04). Cardiologist procedure preference was positively associated with active clinical interpretation of MPS and CCTA (p = 0.03 for the 2 comparisons) but not for ownership of the respective imaging equipment. In conclusion, cardiologist agreement with published AUC ratings is generally high, although physicians classify more uncertain indications as inappropriate. Active clinical interpretation of a procedure contributes most to increased procedure preference.


The impact of type 2 diabetes on numeric pain score reduction following cervical transforaminal epidural steroid injections.
This study aimed to determine whether the presence of type 2 diabetes impairs the therapeutic response to transforaminal cervical epidural steroid injections (TF-CESI) in the treatment of pain due to cervical radiculopathy. This is a retrospective cohort study of patients with cervical radiculopathy who underwent TF-CESI performed by a single physician. Single community-based multidisciplinary pain clinic and ambulatory surgery center. Patients underwent from one to three TF-CESI with dexamethasone or triamcinolone. Change in self-reported numerical pain score. Out of 387 charts reviewed, complete data were available for 329 subjects who underwent TF-CESI from February 2006 through January 2010. The injections consisted of either 40 mg triamcinolone or 15 mg dexamethasone. Of the 329 total subjects, 35 had type 2 diabetes and 294 did not. The diabetic group had a mean age of 58.1 years with standard deviation (SD) of 11.2, mean body mass index (BMI) of 33.1 (SD 7.1), mean pre-procedure pain score of 6.7 (SD 2.2) and mean reduction in pain score of 2.5 (SD 2.4). The non-diabetic group had a mean age of 52.8 (SD 12.4), mean BMI of 28.2 (SD 5.4), mean pre-procedure pain score of 6.7 (SD 1.8), and mean reduction in pain score of 2.4 (SD 2.2). A two-sample t test with equivalent variance showed no statistically significant difference in the mean reduction in pain score between the diabetic and non-diabetic groups. The patients in the diabetic group were typically older and had higher BMIs. The efficacy of TF-CESI for treating cervical radicular pain in this set of 329 patients was independent of the presence of type 2 diabetes.


Mutational analysis of forkhead transcriptional factor 2 (FOXL2) in Korean patients with blepharophimosis-ptosis-epicanthus inversus syndrome.
We screened for mutations in the forkhead transcription factor gene, FOXL2, in Korean patients with sporadic or familial blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) by polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) and direct sequencing. Five of nine BPES families and three of seven sporadic cases were detected to have FOXL2 mutations. We identified four types of FOXL2 mutations, two of which are novel. A new 14 bp deletion (939-952del14) causing a frameshift from G235W and the extension of the predicted protein to 527 amino acids was detected in a BPES family patient. In addition, a novel 845C > A transversion, resulting in a nonsense mutation (S203X), was found in a sporadic case of BPES. The previously reported in-frame 30 bp duplication (909-938dup30) was the most common mutation and was found in eight patients of four BPES families and one sporadic case. A known 17 bp duplication (1080-1096dup17) was observed in a sporadic BPES case. We were unable to find a causal mutation in four BPES families and four sporadic cases. These results suggest that in a fraction of BPES patients, the genetic defect might be associated with a mutation in the non-coding region of the FOXL2 gene or in other genes.


Development of a clinical prediction model for recurrence and mortality outcomes after Clostridioides difficile infection using a machine learning approach.
Clostridioides difficile infection (CDI) is associated with a large burden of morbidity and mortality worldwide. Previous studies have developed models for predicting recurrence and mortality following CDI, but no machine learning predictive models have been developed specifically using data from Japanese patients. Using a database of records from acute care hospitals in Japan, we extracted records from January 2012 to September 2016 (plus a 60-day lookback window). A total of 19,159 patients were included. We used a machine learning approach, XGBoost, and compared it to a traditional unregularized logistic regression model. The first 80% of the dataset (by patient index date) was used to optimize model hyperparameters and train the final models, and evaluation was performed on the remaining 20%. We measured model performance by the area under the receiver operator curve and assessed feature importance using Shapley additive explanations. Performance was similar between the machine learning approach and the classical logistic regression model. Logistic regression performed slightly better than XGBoost for predicting mortality. XGBoost performed slightly better than logistic regression for predicting recurrence, but it was not competitive with existing published models. Despite this, a future machine learning-based application provided in a bedside setting at low cost might be a clinically useful tool.


Genital Mutilation in Males.
Genital mutilation in males can range from minor injuries (cuts from a blade) to severe urological emergencies (testicular or penile amputation). Due to the rarity of these events, there is a lack of extensive reports, as most of the available literature is regarding single cases. Genital mutilation has been associated with psychotic and non-psychotic causes, psychiatric conditions, drug consumption, sexual practices, or even cultural or religious beliefs. It is crucial to perform a psychiatric evaluation of these patients to obtain the best therapeutic approach. This manuscript serves as a review of the currently available knowledge regarding male genital mutilation. A great variety of reasons have been associated with genital mutilation. Previous authors have distinguished between those that present with a clear mental health precursor from cases with no psychotic background. Nevertheless, sometimes, it is difficult to make this distinction. Recently, reconstructive techniques for amputation cases have moved towards a microsurgical approach in order to improve outcomes. A holistic therapeutic approach must be performed to increase the chances of effective treatment. Close collaboration between urologists, psychiatrists, and emergency doctors is essential to ensure the best care for patients performing genital mutilation. Future publications must evaluate differences in treatment options and the impact that these have on the long-term well-being of patients undergoing genital self-mutilation.


Role of phosphate sensing in bone and mineral metabolism.
Inorganic phosphate (Pi) is essential for signal transduction and cell metabolism, and is also an essential structural component of the extracellular matrix of the skeleton. Pi is sensed in bacteria and yeast at the plasma membrane, which activates intracellular signal transduction to control the expression of Pi transporters and other genes that control intracellular Pi levels. In multicellular organisms, Pi homeostasis must be maintained in the organism and at the cellular level, requiring an endocrine and metabolic Pi-sensing mechanism, about which little is currently known. This Review will discuss the metabolic effects of Pi, which are mediated by Pi transporters, inositol pyrophosphates and SYG1-Pho81-XPR1 (SPX)-domain proteins to maintain cellular phosphate homeostasis in the musculoskeletal system. In addition, we will discuss how Pi is sensed by the human body to regulate the production of fibroblast growth factor 23 (FGF23), parathyroid hormone and calcitriol to maintain serum levels of Pi in a narrow range. New findings on the crosstalk between iron and Pi homeostasis in the regulation of FGF23 expression will also be outlined. Mutations in components of these metabolic and endocrine phosphate sensors result in genetic disorders of phosphate homeostasis, cardiomyopathy and familial basal ganglial calcifications, highlighting the importance of this newly emerging area of research.


Computational study of the mechanism of cyclometalation by palladium acetate.
Various mechanisms for the cyclometalation of dimethylbenzylamine by palladium acetate have been studied by DFT calculations. Contrary to previous suggestions, the rate-limiting step is the electrophilic attack of the palladium on an ortho arene C-H bond to form an agostic complex rather than a Wheland intermediate. The cyclometalated product is then formed by intramolecular deprotonation by acetate via a six-membered transition state; this step has almost no activation barrier.


Understanding Variation: Part1- the Run Chart.
This paper briefly describes different types of data, how to collect data, the rationale for organizing data in a time-ordered fashion, and how to use a simple tool called a run chart to present and analyze data. The run chart is simple to construct and equally as simple to analyze. Run charts make variation visible and determine whether a change has made an improvement and if the improvement is being sustained. Two probability rules accompany run charts to help answer the question "How will we know that a change is an improvement?". These rules provide an objective statistical threshold to determine whether changes from quality improvement efforts are having an impact. Quality improvement and data go hand-in-hand. To qualify as quality improvement, projects should have a well-developed data collection and analysis strategy. A run chart and the rules presented in the following paper are simple, statistically valid tools used to answer the question "How will we know that a change is an improvement?".


Demand-driven biogas production from Upflow Anaerobic Sludge Blanket (UASB) reactors to balance the power grid.
Future energy systems necessitate dispatchable renewable energy to balance electrical grids with high shares of intermittent renewables. Biogas from anaerobic digestion (AD) can generate electricity on-demand. High-rate methanogenic reactors, such as the Upflow Anaerobic Sludge Blanket (UASB), can react quicker to variations in feeding as compared to traditional AD systems. In this study, experimental trials validated the feasibility of operating the UASB in a demand-driven manner. The UASB was operated with leachate produced from a hydrolysis reactor treating grass silage. The UASB demonstrated a high degree of flexibility in responding to variable feeding regimes. The intra-day biogas production rate could be increased by up to 123% under 4 hours in demand-driven operation, without significant deterioration in performance. A model based on kinetic analysis was developed to help align demand-driven operation with the grid. The findings suggest significant opportunities for UASBs to provide positive and negative balance to the power grid.


Biodegradable polyglycolide endovascular coils promote wall thickening and drug delivery in a rat aneurysm model.
We designed biodegradable polyglycolide coils (BPCs) and compared the histopathological response to the coils with that to platinum Guglielmi detachable coils (GDCs), after insertion into ligated common carotid arteries (CCAs) of adult rats. BPCs were also tested for use in local drug delivery. Segments (4-mm) of unmodified BPCs, unmodified GDCs, or BPCs coated with Type I bovine collagen and recombinant human vascular endothelial growth factor-165 (500 microg/ml) were inserted into ligated CCAs of adult rats for 14 days, and specimens were compared with contralateral CCA control specimens. Arterial segments with BPCs exhibited substantially increased wall thickening, compared with GDCs (0.33 mm versus 0.10 mm, P < 0.005), which reduced the luminal diameter by 40%, relative to untreated contralateral control specimens (P < 0.05, n = 6). Arterial segments with BPCs also exhibited a marked reduction (P < 0.05, n = 6) in luminal area (0.72 +/- 0.93 mm(2)), with marked cellular proliferation within the coil diameter, indicating coil integration. Arterial segments with collagen/recombinant human vascular endothelial growth factor-coated BPCs also exhibited a marked 2.9-fold increase (P < 0.005, n = 5) in wall thickness (0.29 +/- 0.11 mm) and a 34% reduction in luminal diameter, compared with contralateral control vessels. There was marked proliferation of cells within the coil lumen of vessels treated with BPCs with collagen/recombinant human vascular endothelial growth factor. In this feasibility study, BPCs enhanced the vascular response of CCA segments, compared with GDCs, and were also suitable for local protein delivery to the vessel lumen, under conditions of stasis and arterial pressurization of vascular cells.


Necropsy procedure.
The purpose of this article is to provide guidelines for the necropsy of a calf with diarrhea. Figures and tables are designed to help this procedure. With proper tools and a systematic approach, the entire necropsy should take only 20 to 30 minutes. The efficient and thorough completion of a necropsy often improves the relationship between owner and veterinarian.


Graph-theoretical assignment of secondary structure in multidimensional protein NMR spectra: application to the lac repressor headpiece.
A novel procedure is presented for the automatic identification of secondary structures in proteins from their corresponding NOE data. The method uses a branch of mathematics known as graph theory to identify prescribed NOE connectivity patterns characteristic of the regular secondary structures. Resonance assignment is achieved by connecting these patterns of secondary structure together, thereby matching the connected spin systems to specific segments of the protein sequence. The method known as SERENDIPITY refers to a set of routines developed in a modular fashion, where each program has one or several well-defined tasks. NOE templates for several secondary structure motifs have been developed and the method has been successfully applied to data obtained from NOESY-type spectra. The present report describes the application of the SERENDIPITY protocol to a 3D NOESY-HMQC spectrum of the 15N-labelled lac repressor headpiece protein. The application demonstrates that, under favourable conditions, fully automated identification of secondary structures and semi-automated assignment are feasible.


Integrated environmental factor-dependent growth and arsenic biotransformation by aquatic microalgae: A review.
Arsenic (As) is a toxic metalloid posing harming the human food chain through trophic transfer. Microalgae are primary producers, ensuring bioaccumulation and biogeochemical cycling of As in water environment. They are highly efficient at removing As from the environment, making these microscopic organisms eco-friendly and money saving method in As remediation process. However, microalgal growth and As biotransformation potential relies greatly on individual and integrated environmental factors. This review scrutinizes the available literature on the As biotransformation potentials of various marine and freshwater microalgae under individual and integrated stresses of such factors. Various combinations of important factors such as temperature, salinity, concentrations of As (V) and PO43─, pH, light intensity, and length of exposure period are summarized along with the optimum conditions for different microalgae. The effects of environmental factors on microalgal growth, changes in cell shape, and the relationship between As biotransformation and other activities are discussed in detail. Time-dependent As speciation pattern by aquatic microalgae are reviewed. Conceptual models highlighting the microalgal species particularly linked with environmental factor-dependent As biotransformation mechanisms are also summarized. This review will contribute to an in depth understanding of the connection between environmental factors, As uptake, and the biotransformation mechanism of marine and freshwater microalgae from the perspective of As remediation process.


Promoting Health Equity in the Latinx Community, Locally and Globally: The Duke University School of Nursing Model.
It is imperative that nurses are equipped to promote the health and well-being of diverse populations in United States, including the growing Latinx community, which experiences significant health disparities. This article summarizes the values, programs, and impact of the Duke University School of Nursing Latinx Engagement Health Equity Model. Collaborative partnerships with diverse community partners addressing Latinx populations across the life span were developed, spanning the education, research, and service missions of the university. Programs were rooted in cultural values and were delivered through diverse interprofessional teams and with support from the university. Programs included local and global immersion programs, volunteer work, courses in Medical Spanish, community engaged research projects, and leadership in coalitions. These models have resulted in favorable outcomes for learners, faculty and staff, and the Latinx community more broadly and can serve as a model for strategies to promote health equity at schools of nursing.


Evidence by NMR for mobility of the cytochrome domain within flavocytochrome b2.
According to a model proposed by Gervais, M, Groudinsky, O., Risler, Y. and Labeyrie, F. ((1977) Biochem. Biophys. Res. Commun. 77, 1543-1551) flavocytochrome b2 is composed of a central flavodehydrogenase entity of 4 X 45 kDa to which are attached four cytochrome b2 globules of approx. 11 kDa that are released after proteolysis of the connective loops. A possible inherent mobility of the latter with functional significance was suspected. Proton NMR spectra at 400 MHz of the isolated and of the flavodehydrogenase-bound ferricytochrome b2 units have been compared. In the ranges downfield of +12 ppm and upfield from -4 ppm, where hyperfine-shifted heme proton resonances reside, the chemical shifts are identical for the two forms, but the linewidths are markedly broader for flavocytochrome b2. The linewidths of three heme resonances, a methyl at +19 ppm, two single protons at -6 and -8 ppm (most probably from one vinyl) and an unassigned line at -2.4 ppm, all increase by a factor of about 4. Since, in the present case, linewidths are controlled mainly by proton/proton dipolar relaxations which are caused by molecular tumbling, a change in linewidths of about 15 would be expected if the cytochrome b2 globule had no free motion relative to the flavodehydrogenase domain. The present results thus support the previous hypothesis that such a relative mobility, of unknown correlation time and amplitude, actually exists.


A vaccine combination of lipid nanoparticles and a cholera toxin adjuvant derivative greatly improves lung protection against influenza virus infection.
This is a proof-of-principle study demonstrating that the combination of a cholera toxin derived adjuvant, CTA1-DD, and lipid nanoparticles (LNP) can significantly improve the immunogenicity and protective capacity of an intranasal vaccine. We explored the self-adjuvanted universal influenza vaccine candidate, CTA1-3M2e-DD (FPM2e), linked to LNPs. We found that the combined vector greatly enhanced survival against a highly virulent PR8 strain of influenza virus as compared to when mice were immunized with FPM2e alone. The combined vaccine vector enhanced early endosomal processing and peptide presentation in dendritic cells and upregulated co-stimulation. The augmenting effect was CTA1-enzyme dependent. Whereas systemic anti-M2e antibody and CD4+ T-cell responses were comparable to those of the soluble protein, the local respiratory tract IgA and the specific Th1 and Th17 responses were strongly enhanced. Surprisingly, the lung tissue did not exhibit gross pathology upon recovery from infection and M2e-specific lung resident CD4+ T cells were threefold higher than in FPM2e-immunized mice. This study conveys optimism as to the protective ability of a combination vaccine based on LNPs and various forms of the CTA1-DD adjuvant platform, in general, and, more specifically, an important way forward to develop a universal vaccine against influenza.


Is ABO blood type associated with ovarian stimulation response in patients with diminished ovarian reserve?
Recent studies have explored the relationship between ABO blood type and serum markers of ovarian reserve, specifically follicle-stimulating hormone (FSH) and anti-mullerian hormone (AMH). The primary objective of this study is to investigate whether there is an association between ABO blood type and ovarian stimulation response in patients with serum markers of diminished ovarian reserve (DOR). This is a retrospective study of all patients undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF) between May 2010 and July 2013. Patients were sub-grouped, a priori, based on serum AMH levels: ≤1 ng/mL, ≤0.5 ng/mL and ≤0.16 ng/mL. Within each sub-group, demographic, baseline IVF characteristics and COS response parameters based on ABO blood types were compared. The number of mature oocytes retrieved was considered the primary outcome. Analysis of variance (ANOVA) and Chi-square tests were used to compare means and percentages between ABO blood types within groups. Complete data was available for 2575 patients. The mean (± SD) age and BMI of the study cohort was 38.9 (±3.97) years, 23.4 (±5.91) kg/m(2), respectively. The distribution of ABO blood types in the cohort was as follows: 36.8 % (A), 6.56 % (AB), 17.3 % (B), and 39.3 % (O). The demographics and baseline IVF characteristics were comparable among patients with blood types A, AB, B, and O within each AMH group. Within each AMH sub-group, no difference was found in the total days of COS, total gonadotropins administered, peak estradiol level, or number of mature oocytes retrieved based on blood type. Our results suggest no association between ABO blood type and ovarian stimulation response in patients with DOR. The predictive value of ABO blood type in determining ovarian stimulation response in such patients is currently limited.


Trends in the Impact of Medicaid Expansion on the Use of Clinical Preventive Services.
This study aims to evaluate the trends in the impact of Medicaid expansion on the use of selected recommended clinical preventive services and examine the differences in use by income level over time. The data were obtained from the 2011-2019 Behavioral Risk Factor Surveillance System and were analyzed in 2021. This study conducted a difference-in-differences analysis of the association between Medicaid expansion and the use of 5 clinical preventive services, including colon/breast/cervical cancer screenings, HIV testing, and influenza vaccination. Annual percentage change was applied to assess the trends in the impact of Medicaid expansion on the use of clinical preventive services. The use of all the 5 clinical preventive services varied over time. In almost every year, the use of 4 clinical preventive services (all but HIV testing) among Medicaid expansion states was higher than that among the nonexpansion states. People with lower income used 4 clinical preventive services (all but HIV testing) less frequently than those with higher income, regardless of their residence in expansion or nonexpansion groups. Among the lower-income group, the use of 5 clinical preventive services increased after Medicaid expansion almost every year, with the use of colon cancer screening and HIV testing reaching statistical significance and the impact of Medicaid expansion in the use of each clinical preventive service kept stable from 2014 to 2019. These findings provide evidence that Medicaid expansion may be associated with sustainably increased use of the selected recommended clinical preventive services among the lower-income population and that Medicaid expansion to reduce financial barriers may be an effective strategy to improve population health.


Problems in diagnosis and management of children with cerebral palsy and deafness.
Problems in the diagnosis, management and educational placement of 10 children with cerebral palsy and deafness are reported. Serious inadequacies revealed by the study include delays in diagnosis, poor co-ordination of decision-making between services and frequent changes of school--all leading to unsatisfactory progress by these children.


Accumulation, localisation, and toxic effects of cadmium in the liverwort Lunularia cruciata.
Accumulation, tissue and intracellular localisation, and toxic effects of cadmium were investigated in the liverwort Lunularia cruciata. The results of analyses carried out by atomic absorption spectrometry on single plants showed that the cadmium accumulation was dose- and time-dependent. Cadmium localisation was assessed by X-ray scanning electron microscopy microanalysis in gemmalings and in the different tissues of the thallus and by X-ray transmission electron microscopy microanalysis at the cellular level. The metal preferentially accumulated in the hyaline parenchyma and at the base of the gemma cups. Inside the cell, cadmium accumulated in the vacuoles and the cell wall. Metal accumulation was accompanied by a concomitant increase in sulphur content within the vacuoles of stressed cells. Gel-permeation chromatography showed that most of the cadmium was associated with a low-molecular-mass fraction eluting at a ratio of elution volume to void volume corresponding to that of phytochelatins. The excess of sulphur deposited in the vacuoles may well have been caused by the stress-induced synthesis of phytochelatins. At the ultrastructural level, sublethal concentrations of cadmium caused alterations of the fine structure of the cells, inducing marked alterations of the chloroplast structure. Cadmium also induced a dose-dependent inhibition of apical thallus growth and gemma germination.


Heparin inhibits skeletal muscle growth in vitro.
Heparin or heparan sulfate proteoglycan (HeSPG), but not chondroitin sulfate or hyaluronic acid, exerts a pronounced inhibitory effect on muscle growth in vitro, as determined by total protein, myosin accumulation or synthesis, and [3H]thymidine incorporation studies. Primary muscle fibroblast culture growth is also inhibited by heparin but to a substantially lesser degree compared to muscle (30% and over 90% inhibition of growth, respectively). Heparin-induced inhibition of skeletal muscle growth is a consequence of its interaction with a growth factor(s) present in the media used to support myogenesis; heparin-Sepharose column absorbed horse serum can support muscle growth only in the presence of added heparin-binding growth factors like fibroblast growth factor (FGF) or chicken muscle growth factor (CMGF). Furthermore, heparin prevents the binding of iodinated FGF to the myoblast surface. We also show that the extent of muscle growth is a function of the relative amounts of heparin and FGF in culture. Finally, we provide evidence indicating that FGF can combine with endogenously occurring heparin-like components: immobilized FGF binds sodium-[35S]sulfate labeled components secreted in muscle culture conditioned medium, an interaction inhibited by anti-HeSPG antibodies or heparin, but not by other sulfated glycosaminoglycans. Since heparin binding growth factors not only stimulate myoblast proliferation but also actively inhibit the onset of muscle differentiation (G. Spitzz, D. Roman, and A. Strauss (1986). J. Biol. Chem. 261, 9483-9488), their interaction with naturally occurring heparin-like components may be an important physiological mechanism for modulating muscle growth and differentiation in development and regeneration.


Quantifying Demyelination in NK venom treated nerve using its electric circuit model.
Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.


Actinobacteria from Antarctica as a source for anticancer discovery.
Although many advances have been achieved to treat aggressive tumours, cancer remains a leading cause of death and a public health problem worldwide. Among the main approaches for the discovery of new bioactive agents, the prospect of microbial secondary metabolites represents an effective source for the development of drug leads. In this study, we investigated the actinobacterial diversity associated with an endemic Antarctic species, Deschampsia antarctica, by integrated culture-dependent and culture-independent methods and acknowledged this niche as a reservoir of bioactive strains for the production of antitumour compounds. The 16S rRNA-based analysis showed the predominance of the Actinomycetales order, a well-known group of bioactive metabolite producers belonging to the Actinobacteria phylum. Cultivation techniques were applied, and 72 psychrotolerant Actinobacteria strains belonging to the genera Actinoplanes, Arthrobacter, Kribbella, Mycobacterium, Nocardia, Pilimelia, Pseudarthrobacter, Rhodococcus, Streptacidiphilus, Streptomyces and Tsukamurella were identified. The secondary metabolites were screened, and 17 isolates were identified as promising antitumour compound producers. However, the bio-guided assay showed a pronounced antiproliferative activity for the crude extracts of Streptomyces sp. CMAA 1527 and Streptomyces sp. CMAA 1653. The TGI and LC50 values revealed the potential of these natural products to control the proliferation of breast (MCF-7), glioblastoma (U251), lung/non-small (NCI-H460) and kidney (786-0) human cancer cell lines. Cinerubin B and actinomycin V were the predominant compounds identified in Streptomyces sp. CMAA 1527 and Streptomyces sp. CMAA 1653, respectively. Our results suggest that the rhizosphere of D. antarctica represents a prominent reservoir of bioactive actinobacteria strains and reveals it as an important environment for potential antitumour agents.


Retinal safety evaluation of photoacoustic microscopy.
Photoacoustic microscopy (PAM) has significant potential as a promising diagnostic method for eye diseases and can provide anatomic and functional information of the retinal and choroidal vasculature. However, there are no FDA-approved PAM systems for ophthalmic imaging. In this study, a comprehensive safety evaluation was performed to evaluate the safety of PAM retinal imaging and whether PAM causes damage to retinal structure or function in rabbit eyes. 12 Dutch-Belted pigmented rabbits received photoacoustic imaging to 57% of the retinal surface area with a laser energy of 5% of the ANSI safety limit for five consecutive days and followed before imaging and 3 days, 1, 2, 3, and 4 weeks post imaging. Retinal morphologic analyses using slit lamp examination, fundus photography, red free, FA, FAF, ICGA, and OCT showed no retinal hemorrhage, edema, detachment, vascular abnormalities, or pigmentary abnormalities in the retina or choroid after PAM imaging. Full-field ERG analysis showed no significant difference in scotopic or photopic a- and b-wave amplitudes or implicit times between the control and experimental eyes over time (n = 6, P values > 0.05). Retinal ultrastructural evaluation using TEM showed normal structure of organelles and nuclei, and no significant loss of cells after PAM. TUNEL assay showed no evidence of cells apoptosis in retina. Retinal histopathology indicated that the architecture and thickness of the retinal layers was well preserved in all experimental eyes. A positive control at 500% of the ANSI limit demonstrated significant damage. The comprehensive retinal safety evaluation demonstrated no damage to retinal structure or function for 4 weeks after PAM imaging in rabbits.


High frequency of copy number variations and sequence variants at CYP21A2 locus: implication for the genetic diagnosis of 21-hydroxylase deficiency.
The systematic study of the human genome indicates that the inter-individual variability is greater than expected and it is not only related to sequence polymorphisms but also to gene copy number variants (CNVs). Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD) is the most common autosomal recessive disorder with a carrier frequency of 1:25 to 1:10. The gene that encodes 21-hydroxylase enzyme, CYP21A2, is considered to be one of the most polymorphic human genes. Copy number variations, such as deletions, which are severe mutations common in 21OHD patients, or gene duplications, which have been reported as rare events, have also been described. The correct characterization of 21OHD alleles is important for disease carrier detection and genetic counselling CYP21A2 genotyping by sequencing has been performed in a random sample of the Spanish population, where 144 individuals recruited from university students and employees of the hospital were studied. The frequency of CYP21A2 mutated alleles in our sample was 15.3% (77.3% were mild mutations, 9% were severe mutations and 13.6% were novel variants). Gene dosage assessment was also performed when CYP21A2 gene duplication was suspected. This analysis showed that 7% of individuals bore a chromosome with a duplicated CYP21A2 gene, where one of the copies was mutated. As far as we know, the present study has shown the highest frequency of 21OHD carriers reported by a genotyping analysis. In addition, a high frequency of alleles with CYP21A2 duplications, which could be misinterpreted as 21OHD alleles, was found. Moreover, a high frequency of novel genetic variations with an unknown effect on 21-hydroxylase activity was also found. The high frequency of gene duplications, as well as novel variations, should be considered since they have an important involvement in carrier testing and genetic counseling.


Reduced graphene oxide foam templated by nickel foam for organ-on-a-chip engineering of cardiac constructs.
Myocardial tissue engineering has attracted increasing awareness for heart failure, and researchers are committed to developing an appropriate biological material to reconstruct myocardial tissues. Here, we applied a simple and high-throughput method to fabricate a three-dimensional (3D) partially reduced graphene oxide (PRGO) foam chip, whose structure, properties and biocompatibility confirmed that it is a suitable material for myocardial tissue engineering. The PRGO foam was produced based on a reduction reaction that occurred at the interface between the graphene oxide (GO) solution and Ni foam; as the Ni foam scaffold was dissolved in an HCl solution, the PRGO foam was harvested. After the PRGO foam was freeze-dried, its elasticity property was evaluated, and primary cardiomyocytes obtained from 2-day-old SD rats were cultured in the 3D foam. The results demonstrated good cell adherence, spreading, activity, organization and beating function in the PRGO foam during the long-term culturing process, which proved that the PRGO foam obtained by this method had application potential for myocardial tissue engineering.


Detection of bovine serum albumin in the circulating IgA immune complexes of patients with IgA nephropathy.
Alimentary antigenic challenge has been postulated to have a role in the genesis of IgA circulating immune complexes (CIC), resulting in mesangial IgA disease. In this study, we examined the relationship between bovine serum albumin (BSA) and IgA CIC in patients with IgA nephropathy. Of the 47 patients studied, elevated IgA CIC levels were found in 32% by the F(ab')2 anti-C3 and Raji cell enzyme immunoassays (EIA). Elevated IgA anti-BSA antibody levels were found in 9 patients, and there was a positive correlation between these levels and IgA CIC as measured in the Raji cell EIA (R = 0.60, P less than 0.001). In 4 patients with elevation of both IgA CIC and IgA anti-BSA antibody levels, solubilization experiments were done to demonstrate the presence of BSA antigen in the IgA CIC. Using the Raji cell EIA, the IgA CIC levels decreased significantly after preincubating the sera with serial concentrations of excess BSA. No corresponding effect was seen with human serum albumin used as control. Hence, BSA may be the antigenic stimulus in the formation of IgA CIC in selected patients with IgA nephropathy. The pathogenic capacity of these IgA-BSA CIC remains to be determined.


Enhancers of the PAIR4 regulatory module promote distal VH gene recombination at the Igh locus.
While extended loop extrusion across the entire Igh locus controls VH -DJH recombination, local regulatory sequences, such as the PAIR elements, may also activate VH gene recombination in pro-B-cells. Here, we show that PAIR-associated VH 8 genes contain a conserved putative regulatory element (V8E) in their downstream sequences. To investigate the function of PAIR4 and its V8.7E, we deleted 890 kb containing all 14 PAIRs in the Igh 5' region, which reduced distal VH gene recombination over a 100-kb distance on either side of the deletion. Reconstitution by insertion of PAIR4-V8.7E strongly activated distal VH gene recombination. PAIR4 alone resulted in lower induction of recombination, indicating that PAIR4 and V8.7E function as one regulatory unit. The pro-B-cell-specific activity of PAIR4 depends on CTCF, as mutation of its CTCF-binding site led to sustained PAIR4 activity in pre-B and immature B-cells and to PAIR4 activation in T-cells. Notably, insertion of V8.8E was sufficient to activate VH gene recombination. Hence, enhancers of the PAIR4-V8.7E module and V8.8E element activate distal VH gene recombination and thus contribute to the diversification of the BCR repertoire in the context of loop extrusion.


Serous carcinoma arising from uterine adenomyosis/adenomyotic cyst of the cervical stump: a report of 3 cases.
Serous carcinoma arising in adenomyosis and adenomyotic cyst is very rare. Only 3 serous carcinomas and 5 serous endometrial intraepithelial carcinomas (EIC) have been reported to date. We reviewed the clinicopathological features of 2 serous carcinoma in uterine adenomyosis and 1 serous EIC in adenomyotic cyst of the cervical stump. Case 1 had an endometrial serous carcinoma in the uterine myometrium and the left ovary. A minor component of benign endometrial glands with minimal endometrial stroma was found in the uterine mass and the surrounding myometrium. Case 2 showed 3 small foci of serous carcinoma, serous EIC and endometrial glandular dysplasia (EmGD) in the adenomyosis. Scanty serous carcinoma was present in the endometrium without evidence of myometrial invasion. The eutopic endometrium in both case 1 and 2 had no evidence of neoplastic changes after complete examination. Case 3 had 3 microscopic serous EICs in the adenomyotic cysts of the cervical stump. One EIC lesion coexisted with EmGD. No cancer was found in the endocervical tube although the preoperative endocervical biopsy showed a poorly differentiated endometrioid carcinoma. Immunohistochemistry demonstrated that serous carcinoma in case 1 and EIC in all 3 cases showed a characteristic pattern of p53 and p16 over expression, high Ki67 index, and lack of WT1, ER and PR staining. EmGD in case 1 and 3 had a similar staining pattern except a lower Ki67 index and the presence of ER expression. We believe that this case series may expand our recognition on serous carcinoma arising in uterine adenomyosis/adenomyotic cyst including extra-uterine spread and the potential synchronous growth of carcinomas in eutopic endometrium.


Decalogue to promote the implementation and improvement of recommendations for the early diagnosis of HIV in Emergency Departments.
Early diagnosis of HIV is still a challenge. Emergency Departments (EDs) suppose ideal settings for the early detection of HIV, since patients with high prevalence of hidden HIV infection are frequently attending those services. In 2020, the Spanish Society of Emergency and Emergency Medicine (SEMES) published a series of recommendations for the early diagnosis of patients with suspected HIV infection and their referral and follow-up in the EDs as part of its "Deja tu huella" program. However, the application of these recommendations has been very heterogeneous in our country. Considering this, the working group of the HIV hospital network led by the SEMES has motivated the drafting of a decalogue, with the aim of promoting the implementation and improvement of protocols for the early diagnosis of HIV in Spanish EDs.


Study of factors affecting the antigen structure of the donor kidney. I. Interpretation of the relationship between periodate pretreatment and the rejection phenomena of canine kidney allografts.
Donor kidneys were preserved in a Collins-4 solution containing periodate in concentrations of 10(-2) and 10(-4) mole/l, respectively, in an attempt to oxidize the carbohydrate components of the antigen-carrying membrane surfaces and thus to influence the rejection phenomena exhibited by the allogeneic kidney. All kidneys were, however, rejected as a result of a hyperacute reaction indicating that periodate did not react with the hydrophobic membrane structures in vivo. Not only did the antigen thus remain unchanged but the vulnerability of other renal structures to the destructive effect of the killer cells also increased as a result of toxic damage.


Corrigendum: Antiproliferative effects of the natural oxadiazine Nocuolin A are associated with impairment of mitochondrial oxidative phosphorylation.
[This corrects the article DOI: 10.3389/fonc.2019.00224.].


A novel arrangement of sequence elements surrounding the rDNA promoter and its spacer duplications in tsetse species.
Variation in organization and sequence of the rDNA of six species of tsetse fly (Glossina) has been investigated. Several novel tsetse-specific features have been uncovered. Like many other species the spacer is composed of subrepeats, which in some species contain duplications of the true promoter at the spacer-ETS boundary. In tsetse, however, the first 90 base-pairs of the external transcribed spacer (ETS) (that is, +1 to +90 after transcription initiation) is the 3' end of the last subrepeat. The absence of a "unique" region between the last subrepeat and the ETS suggests that the tsetse rDNA unit may consist of multiple true promoters, that is there is no single ETS boundary. Furthermore, interspecific comparisons show that the 90 base-pair region is part of a conserved 202 base-pair region, consisting of 72 base-pairs upstream from the initiation site and a further 40 base-pairs downstream, which is shared by all promoters other than the last. In genera other than tsetse, subrepeat lengths between species are generally similar; in tsetse they differ due to (1) variation in copy-number of the subsubrepeat motif A9T6CAG, and (2) the presence of large regions flanked by direct simple repeats such as GA5 or TGGTCTC. Slippage-like mechanisms are probably responsible for (1), and recombination and subsequent excision involving the direct repeats for (2). Different structural and sequence variants are seen to be homogenized in the family and fixed in each species, reflecting continual unequal crossing-over. However, notwithstanding this process of differentiation, the available comparisons also reveal that there are two small conserved regions between Glossina and Drosophila: one is part of the promoter and the other is an ETS processing site. Such intergeneric and interspecific differences are discussed in relation to the problem of the maintenance of several essential functions within the rDNA repeating unit despite the continual differentiation of the unit into novel arrangements.


Maximum lesions area and orthogonal values accessed from DWI images would be alternative imaging markers for predicting the outcome of acute ischemia in the middle cerebral artery territory.
Evaluating the acute ischemic volume on diffusion-weighted imaging (DWI) in the middle cerebral artery (MCA) territory would predict outcome. To investigate the correlations between maximum area with restricted diffusion (MaxA), the orthogonal diameters (OD) as well as lesion volume on DWI, and to explore the role of MaxA and OD on predicting unfavorable outcome after an acute MCA ischemic stroke. Sixty consecutive adult patients, including modified Rankin Scale score (mRS) ≤2 (n = 31) and mRS > 2 (n = 29) groups, were retrospectively enrolled. The MaxA and OD of lesions were assessed at the slice containing the largest infarction size on DWI images. We compared the prediction efficiencies of these methods on unfavorable outcomes. The correlation coefficients between the MaxA and infarction volume and OD and infarction volume were 0.982 ( P < 0.001) and 0.952 ( P < 0.001), respectively. The times required for measuring MaxA (150 s [130-160]) and OD (30 s [20-60]) were much shorter than that for infarction volume measurement (1240 s [180-1480]) ( P = 0.001, P = 0.004). With thresholds of ≥57.3 mL for infarction volume, ≥15.2 cm2 for MaxA, and ≥38.1 for the arithmetic product of OD, the AUCs of infarction volume, MaxA, and OD for predicting an unfavorable outcome were 0.818, 0.821, and 0.820, respectively. Since they correlated well with the infarction volume, MaxA and OD assessed on DWI were time-saving and achieved comparable diagnostic efficiencies; thus, they may represent alternative imaging markers for predicting unfavorable outcomes of acute ischemic stroke in MCA territory.


Circadian rhythms govern cardiac repolarization and arrhythmogenesis.
Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease, but the molecular basis of this variation is unknown. A common mechanism that underlies susceptibility to ventricular arrhythmias is abnormalities in the duration (for example, short or long QT syndromes and heart failure) or pattern (for example, Brugada's syndrome) of myocardial repolarization. Here we provide molecular evidence that links circadian rhythms to vulnerability in ventricular arrhythmias in mice. Specifically, we show that cardiac ion-channel expression and QT-interval duration (an index of myocardial repolarization) exhibit endogenous circadian rhythmicity under the control of a clock-dependent oscillator, krüppel-like factor 15 (Klf15). Klf15 transcriptionally controls rhythmic expression of Kv channel-interacting protein 2 (KChIP2), a critical subunit required for generating the transient outward potassium current. Deficiency or excess of Klf15 causes loss of rhythmic QT variation, abnormal repolarization and enhanced susceptibility to ventricular arrhythmias. These findings identify circadian transcription of ion channels as a mechanism for cardiac arrhythmogenesis.


A cell-permeable tool for analysing APP intracellular domain function and manipulation of PIKfyve activity.
The mechanisms for regulating PIKfyve complex activity are currently emerging. The PIKfyve complex, consisting of the phosphoinositide kinase PIKfyve (also known as FAB1), VAC14 and FIG4, is required for the production of phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2]. PIKfyve function is required for homoeostasis of the endo/lysosomal system and is crucially implicated in neuronal function and integrity, as loss of function mutations in the PIKfyve complex lead to neurodegeneration in mouse models and human patients. Our recent work has shown that the intracellular domain of the amyloid precursor protein (APP), a molecule central to the aetiology of Alzheimer's disease binds to VAC14 and enhances PIKfyve function. In the present study, we utilize this recent advance to create an easy-to-use tool for increasing PIKfyve activity in cells. We fused APP intracellular domain (AICD) to the HIV TAT domain, a cell-permeable peptide allowing proteins to penetrate cells. The resultant TAT-AICD fusion protein is cell permeable and triggers an increase in PI(3,5)P2 Using the PI(3,5)P2 specific GFP-ML1Nx2 probe, we show that cell-permeable AICD alters PI(3,5)P2 dynamics. TAT-AICD also provides partial protection from pharmacological inhibition of PIKfyve. All three lines of evidence show that the AICD activates the PIKfyve complex in cells, a finding that is important for our understanding of the mechanism of neurodegeneration in Alzheimer's disease.


Effect of a zinc-deficient diet on mitochondrial and microsomal lipid composition in TEPC-183 plasmacytoma.
A zinc-deficient diet caused an increase in microsomal membrane phospholipid levels compared to ad libitum controls. Cholesterol levels were found to be decreased 50% compared to either pair-fed or ad libitum controls, resulting in a sharp decline in the cholesterol/phospholipid ratio. No differences were observed in the distribution of phospholipid classes among all three groups, either in mitochondrial or microsomal membrane fractions. Fatty acid analysis of PC and PE revealed a rise in the 18:2 fraction from zinc-deficient mitochondrial and microsomal membrane fractions. Mitochondrial PE and PC from zinc-deficient animals revealed a rise in the 22:6 fatty acid fraction while microsomal PC also revealed a corresponding decrease in 20:4. None of the zinc-deficient preparations differed significantly from either ad libitum or pair-fed controls in the content of long-chain alk-l-enyl ethers. The results of this study point to an effect of a zinc-deficient diet on lipid metabolism in tumor subcellular membranes which may account for the decreased rate of tumor growth observed in zinc-deficient animals.


Airway pollution and smoking in reproductive health.
Environmental exposure refers to contact with chemical, biological, or physical substances found in air, water, food, or soil that may have a harmful effect on a person's health. Almost all of the global population (99%) breathe air that contains high levels of pollutants. Smoking is one of the most common forms of recreational drug use and is the leading preventable cause of morbidity and mortality worldwide. The small particles from either ambient (outdoor) pollution or cigarette smoke are inhaled to the lungs and quickly absorbed into the bloodstream. These substances can affect virtually every organ in our body and have been associated with various respiratory, cardiovascular, endocrine, and also reproductive morbidities, including decreased fertility, adverse pregnancy outcomes, and offspring long-term morbidity. This review summarizes the latest literature reporting the reproductive consequences of women exposed to ambient (outdoor) air pollution and cigarette smoking.


Primary palliative care in Japan: needs estimation and projections - national database study with international comparisons.
We aimed to estimate the potential population that requires palliative care, clarify the relationship between this population and the rate of ageing in Japan, and compare these trends with those of other countries. We used the national death registration data and population projections for Japan to estimate the population in need of palliative care using the minimal estimate method developed by Murtagh et al. Linear regression was used to create a model of mortality using sex, age at intervals of 5 years, and each major disease classification. We calculated the future population in need of palliative care until 2040 and compared the ageing data to those of other countries. All adults in Japan who died from 1980 to 2040 at intervals of 5 years. The number of people who might need palliative care from 2020 to 2040 will also increase linearly from 1 059 000 to 1 405 000. The proportion of Alzheimer's, dementia and senility of the total need for palliative care will increase to 43.4% in 2040. The correlation coefficient between the proportion of the population in need of palliative care and the rate of ageing was 0.24 in developed countries. In Japan, the population requiring palliative care in 2040 will be 1.5 times that in 2015. Palliative care needs to be provided urgently for people with Alzheimer's disease, dementia and senility. The proportion of patients in need of palliative care may not change, although the number of patients requiring such gradually increases in developed countries.


Changes in plasma lipoproteins accompanying diet therapy in obese diabetics.
Plasma lipoprotein cholesterol and triglyceride levels were measured in 24 obese not-insulin dependent Pima Indian diabetics and 9 obese nondiabetic controls before and after 1-8 months on a 500 calorie diet. The diabetics were divided into 3 groups--severe, recent onset (n = 10), severe long-term (n = 6), and borderline (n = 8). The diet regimen resulted in weight loss and improved glucose tolerance in all of the diabetics, and insulin secretion increased in the 2 groups of severe diabetics. After the period of weight loss, total plasma cholesterol had declined greater than 20%, and LDL cholesterol decreased 25% in all diabetic groups and in the controls. In all diabetic groups, HDL cholesterol did not decline; therefore the ratio of HDL/LDL cholesterol after diet therapy was significantly increased. In the controls HDL cholesterol declined with weight loss, and the distribution of HDL/LDL cholesterol remained constant. Plasma and VLDL triglyceride levels decreased in all groups in those with initial triglyceride levels greater than 150 mg/dl. The results indicate that weight loss in not-insulin dependent diabetics not only improves glucose tolerance, but also lowerss plasma lipids and reverses the dyslipoproteinemia often associated with this disorder. This may influence the risk of arteriosclerotic heart disease in these individuals.


Hepatic microsomal dealkylations. Inhibition by a tyrosine-copper (II) complex provided with superoxide dismutase activity.
The effect of a divalent copper-tyrosine complex has been evaluated in rat liver microsome-catalyzed dealkylations. The copper complex, which is provided with superoxide dismutase activity, inhibits at micromolar concentrations aminopyrine, p-nitroanisol, and 7-ethoxycoumarin dealkylations. It has also been found that cumene hydroperoxide-supported p-nitroanisol demethylation, the formation of a 440 nm species, and the formation of superoxide radicals are inhibited by the divalent copper complex. On the other hand, 3-chloroperbenzoic acid has been found to support a copper complex-insensitive 7-ethoxycoumarin dealkylation. Oxygen uptake by rat liver microsomes is also inhibited by the copper complex. The data support the concept that the copper complex acts as a superoxide dismutase at the level of a cytochrome P-450 intermediate species, liganded with superoxide anions.


Postnatal maturation of primary afferent terminations in the substantia gelatinosa of the rat spinal cord. An electron microscopic study.
Axodendritic dark sinuous endings occurred on the day of birth (PO) in the synaptic areas of lamina II. These terminals (TI) turned very electron dense and shrunken after capsaicin administration. From day P2, TI-terminals exhibited fluoride-resistant acid phosphatase (FRAP) reactivity. Such findings revealed their origin from primary afferent fine fibers. Dark scalloped, FRAP-reactive, central terminals of type I glomeruli (CI) were first observed on P5. During the ensuing survival times up to P20 an increasing number of CI-terminals seemed to evolve from the less mature TI-endings that gradually disappeared. A few large clear boutons, similar to the central terminals of type II glomeruli (CII) of the adult which arise from thick afferents, were also present in deep lamina II on the day of birth and became more numerous thereafter. From P5, both CI- and CII-endings developed pre- and postsynaptic contacts with vesicle-containing profiles though it was sometimes difficult to distinguish the axonic (V2) from the dendritic (V1-presynaptic dendritic) profiles. CI-boutons established as many presynaptic as postsynaptic contacts with vesicle-containing profiles. In contrast, CII-terminals were mostly postsynaptic to vesicle-containing profiles. Thus, the boutons generated by thin (CI-boutons) and thick (CII-boutons) primary axons gradually develop synapses with vesicle-containing profiles probably arising from local interneurons. The resulting pre- and/or postsynaptic interactions may contribute to the physiological maturation of somatosensory integration that occurs postnatally.


Premium subsidies, the mandate, and Medicaid expansion: Coverage effects of the Affordable Care Act.
Using premium subsidies for private coverage, an individual mandate, and Medicaid expansion, the Affordable Care Act (ACA) has increased insurance coverage. We provide the first comprehensive assessment of these provisions' effects, using the 2012-2015 American Community Survey and a triple-difference estimation strategy that exploits variation by income, geography, and time. Overall, our model explains 60% of the coverage gains in 2014-2015. We find that coverage was moderately responsive to price subsidies, with larger gains in state-based insurance exchanges than the federal exchange. The individual mandate's exemptions and penalties had little impact on coverage rates. The law increased Medicaid among individuals gaining eligibility under the ACA and among previously-eligible populations ("woodwork effect") even in non-expansion states, with no resulting reductions in private insurance. Overall, exchange premium subsidies produced 40% of the coverage gains explained by our ACA policy measures, and Medicaid the other 60%, of which 1/2 occurred among previously-eligible individuals.


Modified Stroop task performance when wearing protective clothing in the heat: An evaluation of the maximum adaptability model.
This exploratory study investigated whether performance in a behavioural inhibition task followed the shape proposed by the Maximum Adaptability Model during progressive exertional heat stress-that is, an initial improvement in cognitive performance is followed by a plateau, and subsequent decline once body temperature continues to rise unabated. Seventeen adult males walked on a treadmill at 4 km h-1 (1% grade) for up to 120 min, in three protective clothing ensembles, across three simulated environments. The simulated environments were equivalent to wet bulb globe temperatures 21, 30 and 37 °C. Cognitive function was assessed using a modified colour-word Stroop Task, with performance expressed as inverse efficiency scores in the simple (congruent) and more complex (incongruent) task conditions. The Stroop Task was completed before a trial, at termination, and every 30 min during walking, and core body temperature was continuously measured. Data were modelled using Bayesian penalised regression, with core body temperature included as a non-linear term (i.e., second degree polynomial). We did not find any evidence that core body temperature had an effect on congruent or incongruent inverse efficiency scores, and no evidence that the relationship between these variables followed the shaped described by the Maximum Adaptability Model. There was, however, evidence that higher pre-exercise serum osmolality values were associated with slower congruent (β = 9.19) and incongruent (β = 8.67) inverse efficiency scores. The posterior probability that these effects were greater than zero was 0.971 and 0.952, respectively. In young, fit men, performance in the behavioural inhibition task was unaffected by increases in body temperature up to 39 °C and did not follow the shape proposed by the Maximum Adaptability Model. A secondary finding of the study was that pre-exercise hydration status affected performance in the inhibition task. Future studies are needed to confirm this result.


Vibrational, conformational and electronic structure investigations of α,α'-dibromo-o-xylene, α,α'-dibromo-m-xylene and α,α'-dibromo-p-xylene.
The Fourier transform infrared (FTIR) and FT-Raman spectra of α,α'-dibromo-o-xylene (DBOX), α,α'-dibromo-m-xylene (DBMX) and α,α'-dibromo-p-xylene (DBPX) of the configuration BrCH(2)C(6)H(4)CH(2)Br have been recorded in the range 4000-400 and 4000-100 cm(-1), respectively. The conformational analysis of these compounds was performed. The complete vibrational assignment and analysis of the fundamental modes of the most stable conformer of the compounds were carried out using the experimental FTIR and FT-Raman data, and quantum mechanical studies. The observed vibrational frequencies were compared with the wavenumbers derived theoretically for the optimized geometry of the compounds from the DFT-B3LYP gradient calculations employing the standard 6-31G**, high level 6-311++G** and cc-pVTZ basis sets. The structural parameters and vibrational wavenumbers obtained from the DFT method are in good agreement with the experimental data. The potential energy distributions of the fundamental modes were also calculated with DFT force fields utilizing Wilson's FG matrix method. The effect of -CH(2)Br group on the skeletal vibrations has been discussed.


Angiogenesis and nerve regeneration in a model of human skin equivalent transplant.
The angiogenesis and reinnervation were studied in a porcine model of human skin equivalent (SE) graft and the relationship between the two processes was investigated. Confocal laser scanning microscopy was used to monitor, during the healing process, the pattern of vascularization and reinnervation at different time points. The SE was obtained by co-culturing fibroblasts and keratinocytes on a collagen-glycosaminoglycan-chitosan biopolymer and grafted on dorsal wounds generated by full-thickness resection in 25/30 Kg Large white pigs. Frozen sections were obtained from biopsies performed in autograft and xenograft, then were immunolabeled by using the endothelial marker lectin Lactifolia and with the neuronal marker gene product PGP9.5. Cajal staining was also used to visualize the nerve fibers. The results show that the vascularization precedes the innervation process. These data are consistent with the view that the development of nervous tissue is driven by nutritional and trophic factors provided by the vascular system. The arborization of the two systems observed during the third week from the graft might play a key role in maintaining the healing process and the graft survival.


Validity of leptin receptor-deficiency (db/db) type 2 diabetes mellitus mice as a model of secondary osteoporosis.
This study aimed to evaluate the validation of the leptin receptor-deficient mice model for secondary osteoporosis associated with type 2 diabetes mellitus (T2DM) at bone micro-architectural level. Thirty three 36-week old male mice were divided into four groups: normal control (db/m) (n = 7), leptin receptor-deficient T2DM (db/db) (n = 8), human C-reactive protein (CRP) transgenic normal control (crp/db/m) (n = 7), and human CRP transgenic T2DM (crp/db/db) (n = 11). Lumber vertebrae (L5) and bilateral lower limbs were scanned by micro-CT to analyze trabecular and cortical bone quality. Right femora were used for three-point bending to analyze the mechanical properties. Trabecular bone quality at L5 was better in db/db or crp/db/db group in terms of bone mineral density (BMD), bone volume fraction, connectivity density, trabecular number and separation (all p < 0.05). However the indices measured at proximal tibia showed comparable trabecular BMD and microarchitecture among the four groups. Femur length in crp/db/db group was significantly shorter than db/m group (p < 0.05) and cortices were thinner in db/db and crp/db/db groups (p > 0.05). Maximum loading and energy yield in mechanical test were similar among groups while the elastic modulus in db/db and crp/db/db significantly lower than db/m. The leptin-receptor mice is not a proper model for secondary osteoporosis associated with T2DM.


Adapted timed up and go: a rapid clinical test to assess gait and cognition in multiple sclerosis.
To measure the Timed Up and Go (TUG), imagined TUG (iTUG), and the difference of time between these two tests (delta time) in 20 patients with relapsing-remitting multiple sclerosis (RRMS) and 20 healthy age-matched controls and to examine whether an association with cognitive functions, motor impairment, and behavioral changes can be determined. The mean ± SD of TUG, iTUG and delta time were used as outcomes. Spatiotemporal gait parameters were recorded by a 12-camera optoelectronic system during straight walking at usual self-selected speed. Cognitive functions were assessed by a standardized neuropsychological examination. Patients performed the TUG slower than the controls (10.00 ± 1.70 s vs. 8.71 ± 1.04 s, p = 0.01, respectively). The TUG was correlated with gait parameters, cognitive functions, and behavior, whereas delta time was correlated only with cognitive functions. TUG represents an interesting test to reveal subtle deficits in RRMS patients with low disability and is related to motor, cognitive, and behavioral functioning. Combining with the TUG, delta time could easily give additional information on specific cognitive functions in the assessment of patients with RRMS.


Systolic time intervals after phenylephrine administration for early stratification of patients after acute myocardial infarction.
This study was designed to assess the usefulness of the changes in left ventricular (LV) systolic time intervals after phenylephrine administration for detecting high-risk patients soon after acute myocardial infarction by correlation with the angiographic and ventriculographic findings. The procedure was performed in 76 consecutive patients (group I) on the fourth postinfarction day and in 12 normal subjects (group II) free of coronary artery disease. In 20 patients with LV ejection fraction < or = 40% (subgroup IA) the preejection period (PEP)/LV ejection time (ET) ratio increased from 0.410 +/- 0.107 to 0.535 +/- 0.102 (p = 0.01) after phenylephrine, whereas in the remaining 56 patients (subgroup IB) with LV ejection fraction > 40% and in the 12 normal subjects the PEP/LVET increased nonsignificantly. Of patients with LV ejection fraction > 40% a subset of 20 patients was distinguished with proximal stenosis in both left anterior descending and either a dominant right or left circumflex coronary artery (subset IB-a). In these the PEP/LVET increased from 0.347 +/- 0.056 to 0.445 +/- 0.019 (p = 0.0001) after phenylephrine, whereas in the remaining 36 patients (subset IB-b) without proximal lesions in 2 main arteries the PEP/LVET increased nonsignificantly. In conclusion, the PEP/LVET response to phenylephrine administration early after acute myocardial infarction is a precise, safe, noninvasive bedside method for early stratification of these patients.


Analysis of haptic perception of materials by multidimensional scaling and physical measurements of roughness and compressibility.
In this paper, results of a free sorting task of 124 different material samples are analysed using multidimensional scaling. The relevant number of dimensions for haptic perception of materials is estimated to be 4. In addition, the haptic material space is calibrated by means of physical measurements of compressibility and roughness. The relation between objective and perceived compressibility and that between objective and perceived roughness could be described by an exponential function.


Triatoma dimidiata (Latreille) abundance and infection with Trypanosoma cruzi in a rural community of Yucatan, Mexico.
The present is a longitudinal study that describes the abundance of Triatoma dimidiata (Latreille) (Hemiptera: Reduviidae) and its infection with Trypanosoma cruzi in a rural community of Yucatan, Mexico. From a total of 370 individuals collected, 81.3% were adults, most from intradomicile ecotope (282/301), but nymphs were more abundant in peridomicile (58/69). The overall proportion of infected bugs was 21.9% (23.9% of adults and 13% of nymphs). The infection proportion was similar between intradomicile and peridomicile ecotopes (22.8% and 18.1%, respectively). Overall, 76.5% (36/47) of the houses and their backyards were infested. Of those, 27.7% were colonized and 75% had infected triatomines. Our data showed different proportions on infestation, colonization and bug density. Ninety-seven percent of overall peridomicile abundance was distributed in chicken coops, doghouses, opossum nests and dove cages. Triatomine entomological indices showed higher infestation and density inside domiciles, but higher colonization in the peridomicile. The abundance, the amount of infected intradomicile adult T. dimidiata and the incidence of infestation showed a seasonal pattern, with 63.7% of all individuals collected during the late dry season (April to June). We showed the peridomicile colonization of animal shelters and suggest it as a relevant source of T. dimidiata individuals. As infected bugs were found in both ecotopes, the studied area is under a high risk of T. cruzi transmission to humans.


Mitochondrial changes in fish cells in vitro in response to serum deprivation.
Mitochondria are critical to cellular activity that implicated in expansive networks to maintain organismal homeostasis under external stimuli of nutrient variability, a common and severe stress to fish performance during the intensive culture conditions. In the present study, zebrafish embryonic fibroblast cells were used to investigate the fish mitochondrial changes upon serum deprivation. Results showed that mitochondrial content and membrane potential were significantly reduced with increased intracellular ROS level in the serum deprivation treated fish cells. And the impaired mitochondria were characterized by rough and fracted outer membrane, and more fused mitochondria were frequently observed with the upregulated mRNA expressions of mitochondrial fusion genes (mfn1b, mfn2, and opa1). Besides, the mitochondrial DNA (mtDNA) copy numbers of mtatp6, mtcox1, mtcytb, mtnd4, and mtnd6 were overall showing the highly significant reduction, together with the mRNA expressions of these genes significantly increased, exhibiting the compensatory effects in mitochondria. Furthermore, the methyl-cytosine of whole mtDNA was compared and the methyl-reads numbers were distinctly increased in the treatment group, reflecting the instability of fish mtDNA with mitochondrial dysfunction under nutrient fluctuations. Collectively, current findings could facilitate the integrated research between fish mitochondrial response and external variables that indicates the potentially profound and durative deficits in fish health during the aquaculture processes.


Comparison of the Intestinal Structure and Intestinal Microbiome between Two Geographically Isolated Populations of Culter alburnus.
Geographical populations of Culter alburnus inhabiting different regions of China present substantial differences in their reproduction and development characters. This study compared the intestinal structures, digestive enzyme activities, and intestinal microbiomes in the Xingkai (XK) Lake and the Dianshan (DS) Lake populations of C. alburnus collected in two isolated and contrasting river systems. We wanted to discover whether the intestinal structure and functional divergence were formed in the two populations due to adaptive evolution caused by geographical isolation. Our study indicated that higher intestinal villi, thicker intestinal mucosa layer and intestinal muscle layer, and significantly higher activity of α-amylase were identified in the XK population. Moreover, quite different intestinal microbiomes were presented in the two populations, with the higher abundance of Bacteroidetes and Firmicutes in the XK population. The significantly different intestinal microbiome in the XK population was functionally enriched in carbohydrate, lipid, and amino acid metabolism by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Our findings indicated that substantial adaptative divergence in the intestinal structures and intestine microbiomes was formed in the two populations due to long-term geographical isolation, which may have strongly affected the digestion and absorption ability of the XK population compared with the DS population.


Ultrasound diagnosis of ureteral stones: its usefulness with subsequent excretory urography.
The diagnostic accuracy of ultrasound scanning and excretory urography was compared in 157 patients with ureteral stones. Over-all, the diagnostic accuracy rates were 78.3 per cent for ultrasound scanning and 81.5 per cent for excretory urography. These rates were 83.2 and 85.0 per cent, respectively, in 107 cases of upper ureteral calculi, and 68.0 and 74.0 per cent, respectively, in 50 cases of lower ureteral stones. When the studies were combined the diagnostic accuracy rates increased to 98.1, 94.0 and 96.8 per cent for upper, lower and all stones, respectively. Ultrasound scanning is useful in the diagnosis of ureteral stones, especially in patients with ureteral colic. However, ultrasound combined with subsequent excretory urography is the most reliable method for the diagnosis of ureteral calculi. Bladder filling is a useful diagnostic aid for ultrasound scanning of lower ureteral calculi.