The impact of border crossing and imprisonment on injection practices and risk of HIV and hepatitis C infection among men who inject drugs in Nepal.
In Nepal, personal drug use is criminalized and among people who inject drugs (PWID), the majority of whom are men, movement across the border with India for drug procurement and use is common. Using a risk environment approach, this study examined associations between border crossing and imprisonment with respect to HIV, HCV and injection risk behavior among men who inject drugs in Nepal. This cross-sectional study analyzed data from 1345 participants from 14 districts across Nepal. Explanatory variables were prior imprisonment and past-month border crossing to procure or use drugs. We used multivariable logistic regression to evaluate associations between these variables and HIV, HCV, HIV/HCV co-infection and past-month injection risk behavior among PWID. Over half of participants reported prior imprisonment (34.6% prior to past year, 21.6% within past year) and Indo-Nepal border crossing in the past year to use or buy drugs (31.2% sometimes, 20.8% often); over one quarter of participants (29.6%) reported both. Imprisonment prior to the past year was associated with higher odds of all outcome variables: HIV (adjusted odds ratio (aOR) 2.44, 95% confidence interval (CI) 1.29-4.59), HCV (aOR 1.51, 95% CI 1.08-2.09), HIV/HCV co-infection (aOR 3.12, 95% CI 1.58-6.14) and injection risk behavior (aOR 1.64, 95% CI 1.20-2.25). Past-year border crossing to procure or use drugs was associated with HCV (aOR 2.06, 95% CI 1.42-2.98) and injection risk behavior (aOR 1.47, 95% CI 1.04-2.10), with larger effect sizes among PWID who reported both border crossing as well as history of imprisonment. Imprisonment and border crossing were associated with injection risk behavior and disease outcomes. These findings indicate a need to implement cross-border disease surveillance and harm reduction initiatives in the Indo-Nepal border region and in Nepali prisons.


Mitotic rounding alters cell geometry to ensure efficient bipolar spindle formation.
Accurate animal cell division requires precise coordination of changes in the structure of the microtubule-based spindle and the actin-based cell cortex. Here, we use a series of perturbation experiments to dissect the relative roles of actin, cortical mechanics, and cell shape in spindle formation. We find that, whereas the actin cortex is largely dispensable for rounding and timely mitotic progression in isolated cells, it is needed to drive rounding to enable unperturbed spindle morphogenesis under conditions of confinement. Using different methods to limit mitotic cell height, we show that a failure to round up causes defects in spindle assembly, pole splitting, and a delay in mitotic progression. These defects can be rescued by increasing microtubule lengths and therefore appear to be a direct consequence of the limited reach of mitotic centrosome-nucleated microtubules. These findings help to explain why most animal cells round up as they enter mitosis.


Conditioning Regimens are Associated with Distinct Patterns of Microbiota Injury in Allogeneic Hematopoietic Cell Transplantation.
The gut microbiota is subject to multiple insults in allogeneic hematopoietic cell transplantation (allo-HCT) recipients. We hypothesized that preparative conditioning regimens contribute to microbiota perturbation in allo-HCT. This was a retrospective study that evaluated the relationship between conditioning regimens exposure in 1,188 allo-HCT recipients and the gut microbiome. Stool samples collected from 20 days before transplantation up to 30 days after were profiled using 16S rRNA sequencing. Microbiota injury was quantified by changes in α-diversity. We identified distinct patterns of microbiota injury that varied by conditioning regimen. Diversity loss was graded into three levels of conditioning-associated microbiota injury (CMBI) in a multivariable model that included antibiotic exposures. High-intensity regimens, such as total body irradiation (TBI)-thiotepa-cyclophosphamide, were associated with the greatest injury (CMBI III). In contrast, the nonmyeloablative regimen fludarabine-cyclophosphamide with low-dose TBI (Flu/Cy/TBI200) had a low-grade injury (CMBI I). The risk of acute GVHD correlated with CMBI degree. Pretransplant microbial compositions were best preserved with Flu/Cy/TBI200, whereas other regimens were associated with loss of commensal bacteria and expansion of Enterococcus. Our findings support an interaction between conditioning at the regimen level and the extent of microbiota injury.


Quality of cancer registry birthplace data for Hispanics living in the United States.
Patient birthplace from the SEER population-based cancer registries is potentially useful for identifying disparities in cancer occurrence and for studying cancer etiology. However, for Hispanics, completeness and accuracy of registry birthplace is unknown. By comparing registry birthplace to self-reported birthplace from 13 interview studies, we determined the completeness and accuracy of this variable and the associations of these measures with patient and hospital characteristics in the Greater Bay Area. Registry birthplace was unrecorded for 46% of 1277 Hispanic cancer cases, and unrecorded birthplace (i.e., incompleteness) was associated with younger age, higher education, English language preference, US birthplace, and admission at certain hospitals. For 691 Hispanics with available registry birthplace, sensitivity and positive predictive value compared to self-report (i.e., accuracy) were 96.3 and 97.3 among foreign-born, and 96.8 and 95.6 among US-born. US-born Hispanics misclassified in the registry as foreign-born were more likely to have unavailable education information, be deceased, prefer a language besides English, and be diagnosed at a smaller hospital or before 1996. Among self-reported foreign-born Hispanics, those misclassified as US-born were less likely to have been diagnosed at an HMO. Although the completeness and accuracy of birthplace information may vary across registries, this variable appears to be limited for analyses involving Hispanics.


Respiratory monitoring of carbon dioxide and oxygen: a ten-year perspective.
During the past 10 years, instrumentation has been developed that can continuously and noninvasively measure changes in carbon dioxide and oxygen. The information generated, which cannot be obtained through the human senses, provides vital clinical data regarding the effectiveness of intubation, ventilation, circulation, oxygenation, and the circuit. This instrumentation plays a major role in decision making both in the safe conduct of anesthesia and mechanical ventilation as well as in the detection and prevention of potentially catastrophic mishaps. For these reasons, a review of what has been learned regarding the instrumentation, collection, and interpretation of the clinical data, and the clinical value of the information is timely. The clinical significance of the carbon dioxide and oxygen waveforms, inspired to expired carbon dioxide and oxygen differences, alveolar-arterial gradients, and global supply-to-demand oxygen relationships measured by capnography, oxygraphy, and pulse oximetry are addressed in this essay.


Alterations in acid-base status and blood gas dynamics during progressive hyperkalaemia in neonatal calves.
Alterations in acid-base status and blood-gas dynamics were studied during induced progressive hyperkalaemia in neonatal calves. The hyperkalaemia was associated initially with respiratory alkalosis in arterial blood when plasma K+ was increased to 6.08 +/- 1.02 mmol litre-1. The rise of plasma K+ above 6.08 +/- 1.02 mmol litre-1 led to the development of metabolic acidosis in arterial and venous blood. There was partial respiratory compensation. Plasma K+ concentrations at or above 11.03 +/- 0.34 mmol litre-1 were associated with a decrease in arterial oxygen tension and arterial oxygen saturation. The oxygen extraction ratio was increased during hyperkalaemia.


Circumcision status and incident herpes simplex virus type 2 infection, genital ulcer disease, and HIV infection.
We assessed the protective effect of medical male circumcision (MMC) against HIV, herpes simplex virus type 2 (HSV-2), and genital ulcer disease (GUD) incidence. Two thousand, seven hundred and eighty-seven men aged 18-24 years living in Kisumu, Kenya were randomly assigned to circumcision (n=1391) or delayed circumcision (n=1393) and assessed by HIV and HSV-2 testing and medical examinations during follow-ups at 1, 3, 6, 12, 18, and 24 months. Cox regression estimated the risk ratio of each outcome (incident HIV, GUD, HSV-2) for circumcision status and multivariable models estimated HIV risk associated with HSV-2, GUD, and circumcision status as time-varying covariates. HIV incidence was 1.42 per 100 person-years. Circumcision was 62% protective against HIV [risk ratio=0.38; 95% confidence interval (CI) 0.22-0.67] and did not change when controlling for HSV-2 and GUD (risk ratio=0.39; 95% CI 0.23-0.69). GUD incidence was halved among circumcised men (risk ratio=0.52; 95% CI 0.37-0.73). HSV-2 incidence did not differ by circumcision status (risk ratio=0.94; 95% CI 0.70-1.25). In the multivariable model, HIV seroconversions were tripled (risk ratio=3.44; 95% CI 1.52-7.80) among men with incident HSV-2 and seven times greater (risk ratio=6.98; 95% CI 3.50-13.9) for men with GUD. Contrary to findings from the South African and Ugandan trials, the protective effect of MMC against HIV was independent of GUD and HSV-2, and MMC had no effect on HSV-2 incidence. Determining the causes of GUD is necessary to reduce associated HIV risk and to understand how circumcision confers protection against GUD and HIV.


Lung radiofrequency ablation: post-procedure imaging patterns and late follow-up.
To describe expected imaging features on chest computed tomography (CT) after percutaneous radiofrequency ablation (RFA) of lung tumors, and their frequency over time after the procedure. In this double-center retrospective study, we reviewed CT scans from patients who underwent RFA for primary or secondary lung tumors. Patients with partial ablation or tumor recurrence during the imaging follow-up were not included. The imaging features were assessed in pre-defined time points: immediate post-procedure, ≤4 weeks, 5-24 weeks, 25-52 weeks and ≥52 weeks. Late follow-up (3 and 5 years after procedure) was assessed clinically in 48 patients. The study population consisted of 69 patients and 144 pulmonary tumors. Six out of 69 (9%) patients had primary lung nodules (stage I) and 63/69 (91 %) had metastatic pulmonary nodules. In a patient-level analysis, immediately after lung RFA, the most common CT features were ground glass opacities (66/69, 96 %), consolidation (56/69, 81 %), and hyperdensity within the nodule (47/69, 68 %). Less than 4 weeks, ground glass opacities (including reversed halo sign) was demonstrated in 20/22 (91 %) patients, while consolidation and pleural thickening were detected in 17/22 patients (77 %). Cavitation, pneumatocele, pneumothorax and pleural effusions were less common features. From 5 weeks onwards, the most common imaging features were parenchymal bands. Our study demonstrated the expected CT features after lung RFA, a safe and effective minimally invasive treatment for selected patients with primary and secondary lung tumors. Diagnostic and interventional radiologists should be familiar with the expected imaging features immediately after RFA and their change over time in order to avoid misinterpretation and inadequate treatments.


Factors affecting the incidence of surgical site infection after geriatric hip fracture surgery: a retrospective multicenter study.
Geriatric hip fracture is a common type of osteoporotic fracture with high mortality and disability; surgical site infection (SSI) can be a devastating complication of this injury. By far, only a few studies identified easily remediable factors to reduce infection rates following hip fracture and less researches have focused on geriatric patients. The objective of this study was to identify potentially modifiable factors associated with SSI following geriatric hip fracture surgery. This retrospective, multicenter study involves three level I hospitals. A total of 1240 patients (60 years or older) underwent hip surgery with complete data were recruited between January 2016 and June 2018. Demographics information, medications and additional comorbidities, operation-related variables, and laboratory indexes were extracted and analyzed. Receiver operating characteristic (ROC) analysis was performed to detect the optimum cut-off value for quantitative data. Univariate and multivariate logistic analysis model were performed respectively to identify the independent predictors. Ninety-four (7.58%) patients developed SSI in this study, and 76 (6.13%) had superficial infection, while 18 (1.45%) were diagnosed with deep infection. Results of univariate and multivariate analysis showed age > 79 years (OR, 2.60; p < 0.001), BMI > 26.6 kg/m2 (OR, 2.97; p < 0.001), operating time > 107 min (OR, 2.18; p = 0.001), and ALB < 41.6 g/L (OR, 2.01; p = 0.005) were associated with an increased incidence of SSI; drainage use (OR, 0.57; p = 0.007) could reduce the incidence of wound infection for patients after geriatric hip fracture. Accurate modifiable variables, operating time > 107 min, serum albumin < 41.6 g/L, BMI > 26.6 kg/m2, and age > 79 years could be applied to distinguish geriatric patients with high-risk of postoperative surgical site infection.


Laryngeal cancer: is computed tomography a valuable imaging technique? A retrospective analysis.
Our objectives were threefold: to evaluate the sensitivity and specificity of laryngeal computed tomography (CT) in the evaluation of laryngeal cancer, to determine the positive and negative predictive values of CT in assessing laryngeal cancer with respect to patient outcome, and to compare the CT staging of laryngeal cancer with endoscopy. We reviewed the records of 77 consecutive patients with endoscopically proven laryngeal cancer. All patients underwent nonhelical CT evaluation of the larynx, with 23 subsequently undergoing surgery and 54 undergoing radiotherapy. The CT findings in the surgical cohort were compared with the pathologic analysis of resected specimens and with endoscopic data using a predetermined checklist of 14 regions of surgical interest. All the CT data in the radiotherapy cohort were compared with patient outcome in an attempt to define regions of tumour involvement that may predict disease recurrence after radiotherapy. CT evaluation of laryngeal cancer had an overall sensitivity of 74% and a specificity of 93%. In the radiotherapy cohort, CT had an overall positive predictive value of 51% and a negative predictive value of 62% for disease recurrence after radiotherapy. Compared with endoscopic examination, CT resulted in upgrading of clinical staging in 43% of patients in the surgical cohort and 33% of patients in the radiotherapy cohort. Our findings suggest that, despite the superiority of CT over endoscopy in the assessment of laryngeal cancer, this imaging technique is weak in staging advanced laryngeal cancer and is poor in predicting clinical outcome following radiotherapy.


Treatment of temporomandibular joint ganglion cyst.
Ganglion cysts of the temporomandibular joint are very rare and always misdiagnosed as synovial cyst, parotid gland tumor, or other cystic lesions. They present with pain, swelling, or dysfunction. Image studies could facilitate to identify the tumor mass from the adjacent soft tissue, but a definitive diagnosis could be made from the pathologic report.A 59-year-old woman presented to the clinics with a chief complaint of a painless swelling mass in the right preauricular region of 3-month duration. Computed tomography was performed, which showed a small radiolucent lesion adjacent to the right condyle. Local excision was performed, and the specimen was sent for histologic examination.Microscopic examination showed a cystic space walled by dense fibrous connective tissue without epithelial or endothelial lining. Immunohistochemical staining of these lining cells showed positivity for vimentin and negativity for cytokeratin. These findings were consistent with the diagnosis of ganglion cyst.Ganglion cysts present as unilobulate or multilobulate cysts that arise from the collagenous tissue and is filled with highly viscous fluid. It does not communicate with the joint cavity. In contrast, synovial cyst is a true cyst lined by cuboidal or flattened cells from the synoviocytes and is filled with gelatinous fluid. It may or may not communicate with the joint cavity. Excision is the treatment of choice of symptomatic cystic lesions. Incomplete excision of these lesions may cause further recurrence or infection. Thus, injection of hydrocortisone or aspiration may be considered as an alternative management.


Transcatheter Arterial Sclerosing Embolization for the Treatment of Giant Propranolol-Resistant Infantile Hemangiomas in the Parotid Region.
To report the effectiveness and safety of transcatheter arterial sclerosing embolization (TASE) for the treatment of parotid infantile hemangiomas that did not respond appreciably to propranolol. A total of 21 infants (12 male and 9 female) with large propranolol-resistant infantile hemangiomas in the parotid region were enrolled in this study. During TASE, the feeding arteries of the lesions were embolized using pingyangmycin-lipiodol emulsion and polyvinyl alcohol particles (300-500 μm) to reduce the blood flow rate. All children were followed up as outpatients at 2 weeks and monthly thereafter. The curative effect was evaluated at the 1- and 3-month follow-up visits. Nine lesions were located on the right side of the parotid gland, whereas 12 were located on the left side. The feeding arteries in all patients originated from branches of the external carotid artery. TASE was technically successful in all patients. The mean (± SD) maximal diameter of the hemangiomas significantly decreased from 6.50 cm ± 2.28 before treatment to 3.56 cm ± 1.84 at 1 month after TASE (P <. 05). Three months after TASE, the mean maximal diameter further significantly decreased to 1.94 cm ± 1.58 (P <. 05). During the follow-up period, 16 cases were rated as excellent and 5 as good; no recurrence or serious complications were noted. Minor side effects, such as slight pain, mild fever, and tissue swelling, were observed. TASE significantly decreased the size of the parotid hemangiomas with minor side effects during a short follow-up period.


Rapid warming and drought negatively impact population size and reproductive dynamics of an avian predator in the arid southwest.
Avian communities of arid ecosystems may be particularly vulnerable to global climate change due to the magnitude of projected change for desert regions and the inherent challenges for species residing in resource limited ecosystems. How arid-zone birds will be affected by rapid increases in air temperature and increased drought frequency and severity is poorly understood because avian responses to climate change have primarily been studied in the relatively mesic northern temperate regions. We studied the effects of increasing air temperature and aridity on a Burrowing Owl (Athene cunicularia) population in the southwestern United States from 1998 to 2013. Over 16 years, the breeding population declined 98.1%, from 52 pairs to 1 pair, and nest success and fledgling output also declined significantly. These trends were strongly associated with the combined effects of decreased precipitation and increased air temperature. Arrival on the breeding grounds, pair formation, nest initiation, and hatch dates all showed significant delays ranging from 9.4 to 25.1 days over 9 years, which have negative effects on reproduction. Adult and juvenile body mass decreased significantly over time, with a loss of 7.9% mass in adult males and 10.9% mass in adult females over 16 years, and a loss of 20.0% mass in nestlings over 8 years. Taken together, these population and reproductive trends have serious implications for local population persistence. The southwestern United States has been identified as a climate change hotspot, with projections of warmer temperatures, less winter precipitation, and an increase in frequency and severity of extreme events including drought and heat waves. An increasingly warm and dry climate may contribute to this species' decline and may already be a driving force of their apparent decline in the desert southwest.


Briarenolides U-Y, New Anti-Inflammatory Briarane Diterpenoids from an Octocoral Briareum sp. (Briareidae).
Five new 13,14-epoxybriarane diterpenoids, briarenolides U-Y (1-5), were isolated from the octocoral Briareum sp. The structures of briaranes 1-5 were elucidated by spectroscopic methods. Briarenolides U-Y (1-5) were found to significantly inhibit the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells.


Brine-induced mortality of non-indigenous invertebrates in residual ballast water.
All transoceanic vessels entering the Great Lakes are required to manage ballast water and ballast tank residuals with ballast water exchange and tank flushing, respectively. While these management procedures effectively reduce the density and richness of biota in ballast waters and thereby reduce the risk of transferring non-indigenous species, some ships are unable to uniformly manage all tanks. Laboratory experiments were conducted to evaluate sodium chloride brine as an emergency treatment for ballast tanks with non-compliant residuals. Invertebrate communities collected from i) Detroit River, ii) exchanged ballast tanks arriving in the Great Lakes, and iii) North Sea ports, were exposed to a range of brine concentrations (15-115‰) until complete mortality was reached. Results indicate that a 1-h exposure to 115‰ brine is a broadly effective treatment (>99.9% mortality) regardless of treatment temperature, taxonomic group, or species' source habitat salinity. A median of 0.00% (range 0.00-5.33) of individuals are expected to survive treatment and the expected number of viable individuals released after treatment is within Canadian and proposed international discharge standards. Before implementation, validation with ship-scale trials is recommended.


Intracranial Hematoma After Ventriculoperitoneal Shunt Placement in a Patient With Factor V Deficiency: A Rare Case Report.
Congenital factor V deficiency (FVD) is a rare bleeding disorder due to an inherited mutation. So far, there are no standard protocols for pre- and peri-operative management of patients with factor V deficiency. This poses a challenge for surgeons and requires a multidisciplinary approach. We present a case of a 60-year-old woman with factor V deficiency admitted to the neurosurgery department of Ibn Tofail Hospital for hydrocephalus requiring a ventriculoperitoneal shunt. Pre-operative management of the patients as well as outcome and follow-up are described and compared with relevant literature.


Food allergy.
Although common, food allergy is vastly overestimated by patients. The main food allergens include cow's milk, eggs, nuts, shellfish and whitefish. Other types of adverse food reactions are numerous; their cause represent a spectrum of toxins, infectious organisms and pharmacologic agents. A definitive diagnosis may be difficult. Recommended measures include prevention through breast feeding, avoidance of known offenders and symptomatic therapy when reactions occur.


Phyto-remediation potential of Ipomoea aquatica for Cr(VI) mitigation.
Phyto-remedial efficiency of Ipomoea aquatica was examined at different experimental conditions for a period of 3 months. This plant was selected due to its easy establishment, tolerance and growing easiness. In all trials, the I. aquatica was grown in coir dust to ensure an inert medium. Essential growth nutrients were supplied externally using Albert solution. Once plant growth conditions were fixed, the model system was spiked with Cr(VI) solution in the range of 7-90 ppm. Up to 28 ppm Cr(VI), I. aquatica exhibits uniform absorption characteristics showing over 75% removal of added Cr(VI). At this stage I. aquatica was not affected and it showed no toxicity symptoms. Therefore, it is suited as a potential phyto-remediant. Further I. aquatica is a vegetable particularly in Asian region; therefore caution has to be taken when selecting it for human consumption due to its high chromium accumulation capacity.


Chitosan-miRNA functionalized microporous titanium oxide surfaces via a layer-by-layer approach with a sustained release profile for enhanced osteogenic activity.
The biofunctionalization of titanium implants for high osteogenic ability is a promising approach for the development of advanced implants to promote osseointegration, especially in compromised bone conditions. In this study, polyelectrolyte multilayers (PEMs) were fabricated using the layer-by-layer approach with a chitosan-miRNA (CS-miRNA) complex and sodium hyaluronate (HA) as the positively and negatively charged polyelectrolytes on microarc-oxidized (MAO) Ti surfaces via silane-glutaraldehyde coupling. Dynamic contact angle and scanning electron microscopy measurements were conducted to monitor the layer accumulation. RiboGreen was used to quantify the miRNA loading and release profile in phosphate-buffered saline. The in vitro transfection efficiency and the cytotoxicity were investigated after seeding mesenchymal stem cells (MSCs) on the CS-antimiR-138/HA PEM-functionalized microporous Ti surface. The in vitro osteogenic differentiation of the MSCs and the in vivo osseointegration were also evaluated. The surface wettability alternately changed during the formation of PEMs. The CS-miRNA nanoparticles were distributed evenly across the MAO surface. The miRNA loading increased with increasing bilayer number. More importantly, a sustained miRNA release was obtained over a timeframe of approximately 2 weeks. In vitro transfection revealed that the CS-antimiR-138 nanoparticles were taken up efficiently by the cells and caused significant knockdown of miR-138 without showing significant cytotoxicity. The CS-antimiR-138/HA PEM surface enhanced the osteogenic differentiation of MSCs in terms of enhanced alkaline phosphatase, collagen production and extracellular matrix mineralization. Substantially enhanced in vivo osseointegration was observed in the rat model. The findings demonstrated that the novel CS-antimiR-138/HA PEM-functionalized microporous Ti implant exhibited sustained release of CS-antimiR-138, and notably enhanced the in vitro osteogenic differentiation of MSCs and in vivo osseointegration. This novel miRNA-functionalized Ti implant may be used in the clinical setting to allow for more effective and robust osseointegration.


Reactive nitrogen species in the chemical biology of inflammation.
The preponderance of epidemiological evidence now points to a strong association between chronic inflammation and cancers of several organs, including the gastrointestinal tract, liver, and lungs. The strongest evidence for a mechanistic link here involves the generation of reactive oxygen and nitrogen species by macrophages and neutrophils that respond to cytokines and other signaling processes arising at sites of inflammation. These reactive species cause oxidation, nitration, halogenation, and deamination of biomolecules of all types, including lipids, proteins, carbohydrates, and nucleic acids, with the formation of toxic and mutagenic products. This review, in honor of Bruce Ames, will focus on recent advances in our understanding of the protein and DNA damage caused by reactive nitrogen species produced by macrophages and neutrophils, with emphasis on nitric oxide, nitrous anhydride, peroxynitrite, and nitrogen dioxide radical.


Small-molecule agonists of mammalian Diaphanous-related (mDia) formins reveal an effective glioblastoma anti-invasion strategy.
The extensive invasive capacity of glioblastoma (GBM) makes it resistant to surgery, radiotherapy, and chemotherapy and thus makes it lethal. In vivo, GBM invasion is mediated by Rho GTPases through unidentified downstream effectors. Mammalian Diaphanous (mDia) family formins are Rho-directed effectors that regulate the F-actin cytoskeleton to support tumor cell motility. Historically, anti-invasion strategies focused upon mDia inhibition, whereas activation remained unexplored. The recent development of small molecules directly inhibiting or activating mDia-driven F-actin assembly that supports motility allows for exploration of their role in GBM. We used the formin inhibitor SMIFH2 and mDia agonists IMM-01/-02 and mDia2-DAD peptides, which disrupt autoinhibition, to examine the roles of mDia inactivation versus activation in GBM cell migration and invasion in vitro and in an ex vivo brain slice invasion model. Inhibiting mDia suppressed directional migration and spheroid invasion while preserving intrinsic random migration. mDia agonism abrogated both random intrinsic and directional migration and halted U87 spheroid invasion in ex vivo brain slices. Thus mDia agonism is a superior GBM anti-invasion strategy. We conclude that formin agonism impedes the most dangerous GBM component-tumor spread into surrounding healthy tissue. Formin activation impairs novel aspects of transformed cells and informs the development of anti-GBM invasion strategies.


Safety of avoiding systemic corticosteroid administration for grade II acute graft-versus-host disease limited to the skin.
We hypothesized that systemic corticosteroid administration would be safely avoided not only in grade I acute graft-versus-host disease (GVHD) but also in selected patients with grade II acute GVHD limited to the skin (grade IIs GVHD). We retrospectively evaluated risk factors for subsequent GVHD progression, defined as the involvement of other organs or progression to grade III to IV GVHD, in 50 patients with acute GVHD of grade IIs at its onset. Sixteen patients received systemic corticosteroid administration before GVHD progression. The cumulative incidence of GVHD progression at 28 days from the onset of grade IIs GVHD was 24%. Twenty-five patients did not require systemic corticosteroid administration throughout the entire episode of acute GVHD. Systemic corticosteroid administration before GVHD progression did not affect GVHD progression, chronic GVHD, or non-relapse mortality. Early onset (less than 26 days from transplantation) of grade IIs GVHD was identified as the only statistically significant risk factor for GVHD progression (hazard ratio 6.73, 95% confidence interval 1.5-31.1, P = 0.01). In conclusion, avoiding systemic corticosteroid administration for selected patients with grade IIs GVHD before GVHD progression did not compromise the transplantation outcomes. Patients with early-onset grade IIs GVHD were at high risk for GVHD progression.


Unilateral restrictive ophthalmoplegia and enophthalmos associated with an intraorbital tissue band.
Fibrosis of the extraocular muscles can be congenital or acquired. Acquired causes include trauma, myositis, thyroid eye disease, infection, and metastases. Congenital fibrosis of the extraocular muscles (CFEOM) runs in families and is known to have a genetic basis. It has been classified by Brown, Hansen, and Harley et al into the five following types: general fibrosis syndrome; fibrosis of the inferior rectus (IR) with blepharoptosis; strabismus fixus; vertical retraction syndrome; and unilateral fibrosis, blepharoptosis, and enophthalmos syndrome. In this report, a case of unilateral fibrosis with enophthalmos and blepharoptosis due to a fibrous band is described.


Antigenicity study of the yeast-generated human parvovirus 4 (PARV4) virus-like particles.
Human parvovirus 4 (PARV4) is a novel tetraparvovirus that was isolated from intravenous drug users in 2005. Recombinant PARV4 capsid protein VP2 can form stable virus-like particles (VLPs) in yeast. These VLPs could act as antigen carriers during vaccine development. Therefore, the information about PARV4 VP2 VLP antigenic sites could advance further research in this area. In this work, human parvovirus 4 VLPs obtained from yeast were used to generate monoclonal antibodies (mAbs) in mice. Epitope mapping of the obtained mAbs showed at least three distinct antigenic sites of the VP2 protein. On top of that, molecular cloning was used to replace PARV4 VP2 antigenic sites with heterologous peptides. The chimeric PARV4 VLPs bearing polyhistidine inserts obtained from yeast were observed using electron microscopy while polyhistidine-specific antibodies detected heterologous peptides of the chimeric VP2 proteins.


Physical activity recommendations from general practitioners in Australia. Results from a national survey.
To identify subgroups of Australian adults likely to receive physical activity advice from their general practitioner and to evaluate the content of the advice provided. Participants (n=1,799), recruited from the Australian Health and Social Science panel, completed an online survey. Signal Detection Analysis was used to identify subgroups that were more/less likely to have received physical activity recommendations. Overall, 18% of participants received a physical activity recommendation from their general practitioner in the past 12 months and eight unique subgroups were identified. The subgroup with the highest proportion (54%) of participants reporting that they received a physical activity recommendation was those with poor physical and mental health-related quality of life and an average daily sitting time of <11 hours. Other subgroups with high proportions of individuals receiving recommendations were characterised by higher weight and/or the presence of co-morbidities. The most commonly prescribed physical activity type was aerobic activity. Few participants received specific physical activity advice. General practitioners are incorporating physical activity promotion into their practice, but primarily as a disease management tool and with limited specificity. Strategies to assist Australian general practitioners to effectively promote physical activity are needed.


Optimized neuronal differentiation of murine embryonic stem cells: role of cell density.
Neuronally differentiated embryonic stem (ES) cells offer a flexible and extremely potent model to study nervous system development and disease. A variety of protocols have been described to facilitate neuronal differentiation. The density of ES cells used for neuronal differentiation has striking effects on the proportion and purity of the derived neuronal cells. Here, the protocols used to optimize ES cell density in neuronal differentiation with and without an initial aggregation step are described.


[Ultrastructural and functional features of the reversibility of sclerotic liver changes in rats treated with exogenous organ specific RNA].
Ultrastructural peculiarities of hepatocytes and Kupffer's cells in rats during the spontaneous reversibility of the experimental cirrhosis of the liver under the usual conditions and also under the influence of exogenous RNA, administered by different methods, were studied. The changes in cell ultrastructure proved to correlate with those of the quantitative indices of the protein synthesizing the liver function during the hepatic cirrhosis reversibility. A positive role of the RNA influence of short duration on the intracellular reparative hepatocytes regeneration, and a negative one in case of RNA influence of long duration was revealed. Participation in the resorption of collagen both of the parenchymal cells and of the stroma was shown.


From pharmacogenomics to translational biomarkers.
There is a need for new biomarkers to enable faster detection of adverse events due to drugs and disease processes. One would prefer biomarkers that are useful in multiple species (i.e., translational or bridging biomarkers) so that it would be possible to directly link responses between species and follow such injury in both preclinical and clinical settings. This chapter will explore some of the issues surrounding the use of pharmacogenomics to identify and qualify such biomarkers, and examples will be provided.


UPLC/ESI-MS/MS analysis of compositional changes for organosulfur compounds in garlic (Allium sativum L.) during fermentation.
In this study, we used liquid chromatography coupled to ion trap mass spectrometry (MS) for the quantification of 11 organosulfur compounds and analysis of their compositional changes in garlic during fermentation using 3 different microbe strains. The calibration curves of all 11 analytes exhibited good linearity (R⩾0.995), and the mean recoveries measured at three concentrations were greater than 81.63% with relative standard deviations of less than 12.79%. Investigation of the compositional changes revealed that the γ-glutamyl peptides content in fermented blanched garlic reduced, whereas the content of the compounds in biosynthesis of S-allyl-l-cysteines from γ-glutamyl peptides increased significantly. Our results also indicated that starter cultures can be used selectively in the production of fermented garlic to increase the amounts of the desired organosulfur compounds.


Double-gap-in-roof reentrant tachycardia following surgical thoracoscopic atrial fibrillation ablation.
A case of macro-reentrant tachycardia associated with a box lesion after thoracoscopis left atrial surgical atrial fibrillation (AF) ablation yet to be described. The goal was to clarify the mechanisms and electrophysiological characteristics of this type of tachycardia. A patient was admitted for an EP study following surgical thoracoscopic AF ablation (box lexion formation by right-sided Cobra thoracoscopic ablation). Thoracoscopic ablation was done as the first step of the hybrid ablation approach to the persistent AF; the second step was the EP study. At the EP study, he presented with incessant regular tachycardia (cycle length of 226 ms). An EP study with conventional, 3D activation and entrainment mapping was done to assess the tachycardia mechanism. Two conduction gaps in the superior line (roofline) between the superior pulmonary veins were discovered. The tachycardia was successfully treated with a radiofrequency application near the gap close to the left superior pulmonary vein; however, following tachycardia termination, pulmonary vein isolation was absent. A second radiofrequency application, close to the roof of the right superior pulmonary, vein closed the gap in the box and led to the isolation of all 4 pulmonary veins. No atrial tachycardia recurred during the 6-month follow-up. Conduction gaps in box lesion created by thoracospcopic ablation can present as a novel type of man-made tachycardia after surgical ablation of atrial fibrillation. Activation and entrainment mapping is necessary for an accurate diagnosis.


New assays for the enzymatic conversion of cholesterol to pregnenolone.
Cholesterol side chain cleavage is determined by means of separation of (26-C14)-cholesterol and its radioactively labeled side chain (1-C14)k-isocaproic acid. Alumina minicolumn assay (AMCA): adsorption of cholesterol from an aqueous phase by aluminium oxide, while isocaproic acid can percolate through the column. In modification of a previously described technique (1), cholesterol is quantitatively eluted by ethanol. Filter assay (FA): retention of cholesterol by a membrane filter (pore size less than or equal to 0.1 um) while isocaproic acid can pass the filter. Two-phase scintillation assay (TPSA): pH-dependent partition of isocaproic acid between an organic scintillation mixture and an aqueous phase. The TPSA can be applied for all enzymatic reaction in which the polarity of the radioactive residue which is split off depends on pH values or when the total charge of a polar molecule is changed to an apolar state by cleaving one non-radioactive group (e.g. steroid sulfates) and vice versa. The criteria or reliability of the test systems are described. Bovine adrenal mitochondria were incubated and the side chain cleavage of (26-C14)-cholesterol was studied by the new tests systems and compared to the conversion rates of (4-C14)-cholesterol to its metabolites are determined by thin layer chromatography. A good agreement of all tests was found.


The impairing effects of chaetochromin D on mitochondrial respiration and structure.
Chaetochromin D, a toxic secondary metabolite ofChaetomlum graclle, was examined for impairing effects on mitochondrial respiration and structure (swelling-induction) using isolated rat liver mitochondria to gain Insight into the molecular mechanism for Its cytotoxicity. Chaetochromin D exerted similar mode of effects to those of chaetochromin A, cephalochromin, and ustilaginoldin A on mitochondrial reactions, causing uncoupling of oxidative phosphorylation, depression of state 3 respiration, and induction of drastic swelling In mitochondria.Chaetochromin D induced the same style of swelling as that induced by chaetochromin A, being characterized by a very high rate and small amplitude of swelling. The swelling terminated In the middle and the amplitude was about half of the full swelling. Once the quick swelling ceased in the middle, subsequent swelling could not be elicited by the second addition of chaetochromin D at any of the concentrations tested.


Characterization of glycoproteins isolated from porcine zonae pellucidae.
Two glycoproteins, tentatively designated as PZ-alpha and PZ-beta, have been isolated and purified to homogeneity from porcine zonae pellucidae by a simple purification procedure producing a high yield. The procedure included the dissolution of the zona material in 0.1 M sodium borate buffer pH 10.0, Sephadex G-100 column chromatography and preparative SDS-polyacrylamide gel electrophoresis. The purified glycoproteins gave a single band on polyacrylamide gel and had molecular weights of 60 000 (PZ-alpha) and 96 000 (PZ-beta). Glutamic acid was detected as the NH2-terminal residue in both glycoproteins, using the dansyl chloride method. Though their amino acid compositions were similar, their carbohydrate contents were slightly different (PZ-alpha: 24.9%; PZ-beta; 19.6%), but these components contained the same types of monosaccharides: fucose, mannose, galactose, NAcGlc and sialic acid. The antigenic properties of the two glycoproteins were indistinguishable by immunodiffusion tests. The PZ-beta could be converted in part to smaller molecular weight components, though not to PZ-alpha, by treatment with beta-mercaptoethanol. Thus clear differences between PZ-alpha and PZ-beta could not be detected by chemical or immunological analyses except for the difference in the behaviour on SDS-polyacrylamide gel electrophoresis.


Photodynamic therapy of DNA mismatch repair-deficient and -proficient tumour cells.
Loss of DNA mismatch repair is a common finding in hereditary nonpolyposis colon cancer as well as in many types of sporadic human tumours. DNA mismatch repair-deficient cells have been reported to be resistant to many chemotherapeutic agents and to radiotherapy, and to have the potential of rapidly acquiring additional mutations leading to tumour progression. Photodynamic therapy is a new treatment modality using light to activate a photosensitiser that preferentially localises in tumour cells. An oxygen dependent photochemical reaction ensues, resulting in selective tumour necrosis. The effect of loss of DNA mismatch repair activity on the sensitivity to photodynamic therapy was tested using pairs of cell lines proficient or deficient in mismatch repair due to loss of either MLH1 or MSH2 protein function. Cells were incubated with the photosensitiser 5,10,15,20-meta-tetra(hydroxyphenyl)chlorin and exposed to laser light at 652 nm with various optical doses ranging from 0-1 J cm(-2). Cell survival was assessed using the clonogenic assay. Loss of MLH1 or MSH2 function was not associated with resistance to photodynamic therapy. MCF-7 cells repeatedly treated with photodynamic therapy expressed parental levels of MLH1, MSH2, MSH6, and PMS2. DNA mismatch repair-deficient and -proficient cells showed similar subcellular distributions of meta-tetra(hydroxyphenyl)chlorin as analysed by laser scanning and fluorescence microscopy. Therefore, repeated exposure of tumour cells to photodynamic therapy does not seem to result in loss of DNA mismatch repair, and loss of mismatch repair, in turn, does not seem to contribute to resistance to photodynamic therapy. Our results suggest recommending photodynamic therapy as a strategy for circumventing resistance due to loss of DNA mismatch repair.


Maternal diabetes and risk of childhood acute lymphoblastic leukaemia in the offspring.
Maternal diabetes may be linked to childhood acute lymphoblastic leukaemia (ALL) in the offspring. We assessed the association between maternal pregestational or gestational diabetes and offspring risk of childhood ALL in a register-based study, including all singletons born in Denmark during 1996-2015 (n=1 187 482). Adjusted hazard ratios of childhood ALL were 2.91 (95% confidence interval (CI): 1.30-6.51) for maternal pregestational diabetes and 1.75 (95% CI: 1.02-2.98) for maternal gestational diabetes. Paternal diabetes did not alter offspring ALL risk, and we found no association between offspring ALL and later maternal risk of diabetes. Regardless that absolute ALL risk among offspring of women with diabetes remains low, our findings suggest that characteristics of the diabetic intrauterine environment promote ALL development. This offers a setting for future research into the biological mechanisms underlying childhood ALL.


The effect of H3O+ on the membrane morphology and hydrogen bonding of a phospholipid bilayer.
At the 2017 meeting of the Australian Society for Biophysics, we presented the combined results from two recent studies showing how hydronium ions (H3O+) modulate the structure and ion permeability of phospholipid bilayers. In the first study, the impact of H3O+ on lipid packing had been identified using tethered bilayer lipid membranes in conjunction with electrical impedance spectroscopy and neutron reflectometry. The increased presence of H3O+ (i.e. lower pH) led to a significant reduction in membrane conductivity and increased membrane thickness. A first-order explanation for the effect was assigned to alterations in the steric packing of the membrane lipids. Changes in packing were described by a critical packing parameter (CPP) related to the interfacial area and volume and shape of the membrane lipids. We proposed that increasing the concentraton of H3O+ resulted in stronger hydrogen bonding between the phosphate oxygens at the water-lipid interface leading to a reduced area per lipid and slightly increased membrane thickness. At the meeting, a molecular model for these pH effects based on the result of our second study was presented. Multiple μs-long, unrestrained molecular dynamic (MD) simulations of a phosphatidylcholine lipid bilayer were carried out and showed a concentration dependent reduction in the area per lipid and an increase in bilayer thickness, in agreement with experimental data. Further, H3O+ preferentially accumulated at the water-lipid interface, suggesting the localised pH at the membrane surface is much lower than the bulk bathing solution. Another significant finding was that the hydrogen bonds formed by H3O+ ions with lipid headgroup oxygens are, on average, shorter in length and longer-lived than the ones formed in bulk water. In addition, the H3O+ ions resided for longer periods in association with the carbonyl oxygens than with either phosphate oxygen in lipids. In summary, the MD simulations support a model where the hydrogen bonding capacity of H3O+ for carbonyl and phosphate oxygens is the origin of the pH-induced changes in lipid packing in phospholipid membranes. These molecular-level studies are an important step towards a better understanding of the effect of pH on biological membranes.


Extranodal Rosai-Dorfman Disease as Isolated Lesion of the Tibia Diagnosed by Fine-Needle Aspiration Cytology: A Case Report.
Few studies have used fine-needle aspiration cytology for the purpose of isolated skeletal Rosai-Dorfman diseases (RDDs) diagnosis.Herein, we described an extremely rare case of a 56-year-old woman who presented to our hospital with an insidious onset of pain in the right proximal tibia.The provisional cytologic diagnosis of RDDs was confirmed by a computer tomography-guided core needle biopsy of the lesion. Subsequently, curettage and autogenous iliac crest bone graft were performed successfully. At the 4th year of follow-up her clinical symptoms disappeared, and there was no clinical evidence of lesion recurrence.Our case highlighted the role of fine-needle aspiration cytology with immunohistochemical studies in the diagnosis of RDDs and the characteristic features of isolated skeletal RDDs in an unusual location, the knowledge of which would help avoid missed or delayed diagnosis in the future.


Relationship between SWAP-200 patient personality characteristics and patient-rated alliance early in treatment.
Research on the therapeutic alliance suggests patient personality characteristics to be plausible correlates of alliance formation. To date, research has largely focused on the relationship between the alliance and facets of patient personality measured via patient self-report, versus personality syndromes.In the present study, we assess patient personality using a clinician-rated measure-the Shedler-Westen Assessment Procedure-200 (SWAP-200; Shedler and Westen [Assessment 5:335-355, 1998; Am J Psychiatry 161:1350-1365, 2004; Am J Psychiatry 161:1743-1754, 2004]; Westen and Shedler [Am J Psychiatry 156:258-272, 1999; Am J Psychiatry 156:273-285, 1999])-and investigate the extent to which empirically derived personality configurations correlate with patient-rated alliance. The study sample consisted of 94 patients receiving psychodynamic psychotherapy at an outpatient clinic.The SWAP-200 Dependent Clinical Prototype and Dysphoric: Dependent-Masochistic Q-Factors were found to significantly correlate with early alliance. Also identified were specific SWAP-200 items that independently correlated with early alliance scores.The results of the present study demonstrate a relation between patient personality characteristics and therapeutic alliance that may serve to further a conceptual understanding of the alliance.


Concomitant mitral valve repair and left ventricular reconstruction in a patient with chronic ischemic mitral regurgitation and inferior left ventricular aneurysm.
The surgical approach to ischemic mitral regurgitation with concomitant inferior left ventricular aneurysm remains uncertain in terms of the indication for operation and the short- and long-term outcomes. We performed concomitant mitral valve repair, left ventricular reconstruction, and aortic valve replacement on a 71-year-old male with severe ischemic mitral regurgitation, inferior left ventricular aneurysm, and degenerative aortic regurgitation. Postoperative status was in New York Heart Association functional class I without mitral regurgitation 8 months after operation. We discuss, and review the procedures reported in the literature.


Nerve growth factor-induced increase in [3H]thymidine incorporation into parotid and submandibular glands of young rats and its partial blockade by propranolol or partial sialoadenectomy.
Administration of nerve growth factor (NGF) twice daily for 2 days to young rats (11 days old at the time of the initial injection) resulted in an 8.1-fold increase in [3H]thymidine levels of the parotid gland, and a 9.7-fold increase in levels of the submandibular gland when compared to untreated controls. Isoproterenol (ISO), a beta-adrenergic receptor agonist, caused an 8.7-fold increase in [3H]thymidine incorporation into DNA of the parotid gland, and a 10.7-fold increase in [3H]thymidine in the submandibular gland when compared to controls. The increase in thymidine was accompanied by parotid gland enlargement as well as an increase in cell surface beta 1-4 galactosyltransferase, an enzyme whose expression has been associated previously with acinar cell proliferation. Administration of NGF and ISO together were not additive in their effects on the parotid and submandibular glands. The introduction of propranolol, a beta-adrenergic receptor antagonist, completely negated the ISO effects on the salivary glands but was only partially effective in blocking the NGF effects on the glands. An assay of parotid levels of norepinephrine showed NGF treatment to cause an increase in gland-associated levels of neurotransmitter. Removal of the submandibular/sublingual glands prior to administration of ISO prevented the above changes in the parotid gland. NGF administered to partially sialoadenectomized rats was also less effective in inducing parotid gland hypertrophy and hyperplasia. Simultaneous administration of NGF and ISO to the partially sialoadenectomized rats had an additive influence on [3H]thymidine incorporation, galactosyltransferase expression and gland hypertrophy. The results suggest that NGF influences salivary gland cell growth in part through activation of cell-surface beta-adrenergic receptors.


Transitioning to sustainable dietary patterns: learnings from animal-based and plant-based dietary patterns in French Canadian adults.
Many dietary guidelines promote the substitution of animal proteins with plant-based proteins for health benefits but also to help transitioning toward more sustainable dietary patterns. The aim of this study was to examine the food and nutrient characteristics as well as the overall quality and costs of dietary patterns consistent with lower intakes of animal-based protein foods and with higher intakes of plant-based protein foods among French Canadian adults. Dietary intake data, evaluated with 24 h recalls, from 1,147 French-speaking adults of the PRÉDicteurs Individuels, Sociaux et Environnementaux (PREDISE) study conducted between 2015 and 2017 in Québec were used. Usual dietary intakes and diet costs were estimated with the National Cancer Institute's multivariate method. Consumption of animal- and plant-based protein foods was classified into quarters (Q) and differences in food and nutrient intakes, Healthy Eating Food Index (HEFI)-2019 scores and diet costs across quarters were assessed using linear regression models adjusted for age and sex. Participants with lower intakes of animal-based protein foods (Q1 vs. Q4) had a higher HEFI-2019 total score (+4.0 pts, 95% CI, 0.9 to 7.1) and lower daily diet costs (-1.9 $CAD, 95% CI, -2.6 to -1.2). Participants with higher intakes of plant-based protein foods (Q4 vs. Q1) had a higher HEFI-2019 total score (+14.6 pts, 95% CI, 12.4 to 16.9) but no difference in daily diet costs (0.0$CAD, 95% CI, -0.7 to 0.7). In a perspective of diet sustainability, results from this study among French-speaking Canadian adults suggest that a shift toward a dietary pattern focused primarily on lower amounts of animal-based protein foods may be associated with a better diet quality at lower costs. On the other hand, transitioning to a dietary pattern focused primarily on higher amounts of plant-based protein foods may further improve the diet quality at no additional cost.


Free-breathing three-dimensional isotropic-resolution MR sequence for simultaneous vessel wall imaging of bilateral renal arteries and abdominal aorta: Feasibility and reproducibility.
Many diseases can simultaneously involve renal arteries and the adjacent abdominal aorta. This study proposed a free-breathing three-dimensional (3D) isotropic-resolution magnetic resonance sequence for simultaneous vessel wall imaging (VWI) of bilateral renal arteries and adjacent abdominal aorta. A respiratory-triggered isotropic-resolution sequence that combined the improved motion-sensitized driven-equilibrium (iMSDE) preparation with the spoiled gradient recalled (SPGR) readout (iMSDE-SPGR) was proposed for simultaneous VWI of renal arteries and abdominal aorta. The proposed iMSDE-SPGR sequence was optimized by positioning spatial saturation pulses (i.e., REST slabs) elaborately to further alleviate respiratory and gastrointestinal motion artifacts and selecting appropriate first-order gradient moment (m1 ) of the iMSDE preparation. Thirteen healthy subjects and 13 patients with renal artery stenosis underwent simultaneous VWI with the optimized iMSDE-SPGR sequence at 3.0 T. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and morphology of renal arterial wall and aortic wall were measured. Reproducibility of intra-observer, inter-observer, and scan-rescan (n = 13 healthy subjects) in measuring SNR, CNR, and morphology was evaluated. For the reproducibility test, the agreement was determined using intraclass correlation coefficients (ICC), and the differences were compared using paired t-test or nonparametric Wilcoxon test when appropriate. Bland-Altman plots were used to calculate the bias between observers and between scans. The proposed iMSDE-SPGR sequence was feasible for simultaneous VWI both in the healthy subjects and the patients. The sequence showed good to excellent inter-observer (ICC: 0.615-0.999), excellent intra-observer (ICC: 0.801-0.998), and scan-rescan (ICC: 0.768-0.998) reproducibility in measuring morphology, SNR, and CNR. There were no significant differences in SNR, CNR, and morphology measurements between observers and between scans (all p > 0.05). Bland-Altman plots showed small bias in assessing SNR, CNR, and morphology. The proposed free-breathing 3D isotropic-resolution iMSDE-SPGR technique is feasible and reproducible for simultaneous VWI of bilateral renal arteries and adjacent abdominal aorta.


[Results of 5 campaigns to detect previously unidentified cases of hypertension].
To find the efficacy of two methods of detecting previously unknown hypertension--systematic taking of blood pressure (ST) and the Mobile Unit (MU)--and to evaluate the over-diagnosis of arterial hypertension (AHT) in crossover studies which only use epidemiological criteria (EC). A descriptive study with population and opportunist strategies. An operative MU team attended commercial and work centres within the chosen area. ST looked for AHT in patients attending Health Centre clinics. EC in screening, in line with WHO guidelines and clinical confirmation (CC) in the Health Centres. MU in the catchment areas of Novelda, Carrús and C. Jardin Health areas. ST in the San Miguel de Salinas and C. Jardin Health Centres. 1654 people over 19 with the MU and 4138 through ST. Both methods discovered more hypertension in men (MU p = 0.009 and ST p = 0.000) and in the 20 to 39 age group (MU p = 0.000 and ST p = 0.000). EC led to over-diagnosis (5.8% MU and 6.3% ST); greater in men (6.6% and 6.5%) and +/- 60 years old (8.7% and 7.5%). Positive predictive values obtained were 59.8% with MU and 47.4% with ST. Both methods are useful ways of identifying people suffering hypertension: both young people and men. But CC is essential in order to make a real diagnosis of AHT. Out of every 10 people detected by using EC, only 5 were confirmed by ST and 6 by MU. This information must be borne in mind when evaluating the the prevalence of AHT in epidemiological studies.


Determination of decarbamoyl saxitoxin and its analogues in shellfish by prechromatographic oxidation and liquid chromatography with fluorescence detection.
Oxidation and chromatographic conditions for detecting the decarbamoyl analogues of several paralytic shellfish poison (PSP) toxins were studied. Prechromatographic oxidation with periodate or hydrogen peroxide under slightly alkaline conditions was used as previously reported for the parent PSP toxins. Both periodate and hydrogen peroxide oxidations produced 2 fluorescent products separable by liquid chromatography for each decarbamoyl (dc) toxin (dc-saxitoxin, dc-neosaxatoxin and dc-gonyautoxins 2 and 3). Decarbamoyl saxitoxin produced the same 2 products as did dc-neosaxitoxin but in different ratios. One of these products was the same as the one obtained with neosaxitoxin after periodate oxidation. Decarbamoyl gonyautoxins 2 and 3 (together) produced 2 products, one of which was the same as the major product obtained with gonyautoxins 1 and 4 (together) after periodate oxidation. Decarbamoyl gonyautoxins 1 and 4 were not available for study. The method was used to detect dc-saxitoxin and dc-gonyautoxins 2 and 3 in shellfish extracts.


A semi-automated procedure for aiding the diagnosis of cervical neoplasms based on the measurement of acid-labile DNA in exfoliated cells.
Measurements of acid-labile fractions of DNA in cells exfoliated from cervical neoplasms (invasive squamous-cell carcinomas) using Feulgen techniques have shown elevated values in both abnormal and cytologically normal cell nuclei. These increased values occur early in the hydrolysis profiles before the Feulgen hydrolysis optimum for the cell nuclei of normal patients has been attained. They are of sufficient magnitude to enable a microcomputer programmed in BASIC to distinguish between normal and abnormal cells, even when the latter are of cytologically normal appearance. By semi-automating the measurement procedure using a microcomputer interfaced with a Vickers M86 microdensitometer, the assessment of acid-labile DNA in cell nuclei is proposed as a useful aid to the existing cytological diagnosis of cervical neoplasms.


New, simple model of mesenteric lymph node metastases in the rat.
Injection of 1 x 10(6) CC531 colonic carcinoma cells into the mesenteric lymph nodes of Wag/Rij rats resulted in the growth of tumors within the lymph nodes. These were apparent after 3 days, whereas lung and liver metastases were not observed until 5 weeks after inoculation. In vivo labeling with bromodeoxyuridine (BrdU) followed by immunostaining with an anti-BrdU monoclonal antibody showed a marked difference in the proportion of labeled cells of the metastases at different times after inoculation: after 3 days, many tumor cells but also many stromal cells were labeled; after 7 and 11 days, however, far less stromal cells were positive, most labeled cells being tumor cells.


Caring for the Caregivers: An Alzheimer Disease Research Center Call to Action.
Currently, over 16 million dementia caregivers in the US provide over 18 billion hours of care. As the number of persons living with dementia increases, so too will the number of family caregivers. Given the projected steady growth in caregivers and their health-related needs in caring for persons living with Alzheimer disease and related dementias, several initiatives are underway that focus on caregivers. One overlooked mechanism to meet caregiver needs is the National Institute on Aging's Alzheimer's Disease Research Centers (ADRCs). Through secondary analysis, we present a picture of dementia caregiving from the National Alzheimer's Coordinating Center's database and discuss a call to action for ADRCs to engage caregivers and further support the mission of the ADRC to advance the field of dementia research.


Molecular action of aldosterone.
Aldosterone stimulates the reabsorption of sodium across epithelial cells of various target tissues. The initial events in the molecular action of the mineralocorticoid are the following: (1) Diffusion of the steroid across the cellular (baso-lateral, serosal) plasma membrane into the cytoplasmic compartment. (2) Binding of the steroid to a receptor protein specific for the class of steroid and activation of this steroid-receptor-complex. (3) Translocation of the activated aldosterone-receptor complex to the nucleus and stimulation of RNA synthesis (including the synthesis of messenger RNA and ribosomal RNA). (4) Translation of the steroid-induced messenger RNAs at the ribosomal level into the aldosterone-induced proteins (AIP) within the cytoplasmic compartment. Whereas these induction steps are uniformly accepted, the mechanisms by which the AIPs increase the activity of a rate-limiting step in the sodium transport process are still object of debate. In this paper we discuss the initial events in the mode of action of aldosterone and the biochemical and physiological approaches to the aldosterone-induced proteins with special reference to the "sodium permease", the "energy", and the "sodium pump" theory. Our analysis shows that despite serious efforts by multiple laboratories, the first AIP with an established relationship to the mineralocorticoid actions of aldosterone is yet to be identified.


Route of Zika virus infection in Aedes aegypti by transmission electron microscopy.
Zika fever has been a global health security threat, especially in the tropical and subtropical regions where most of the cases occur. The disease is caused by Zika virus (ZIKV), which belongs to the family Flaviviridae, genus Flavivirus. The virus is transmitted by Aedes mosquitoes, mostly by Aedes aegypti, during its blood meal. In this study we present a descriptive analysis, by transmission electron microscopy (TEM), of ZIKV infection in A. aegypti elected tissues at the 3rd day of infection. ZIKV vertical transmission experiments by oral infection were conducted to explore an offspring of natural infection. Gut and ovary tissues harbored a higher number of viral particles. The ZIKV genome was also detected, by RT-qPCR technique, in the organism of orally infected female mosquitoes and in their eggs laid. The data obtained suggest that the ovary is an organ susceptible to be infected with ZIKV and that virus can be transmitted from mother to a fraction of the progeny.


Neglected waterborne parasitic protozoa and their detection in water.
Outbreak incidents raise the question of whether the less frequent aetiological agents of outbreaks are really less frequent in water. Alternatively, waterborne transmission could be relevant, but the lack of attention and rapid, sensitive methods to recover and detect the exogenous stages in water may keep them under-recognized. High quality information on the prevalence and detection of less frequent waterborne protozoa, such as Cyclospora cayetanensis, Toxoplasma gondii, Isospora belli, Balantidium coli, Blastocystis hominis, Entamoeba histolytica and other free-living amoebae (FLA), are not available. This present paper discusses the detection tools applied for the water surveillance of the neglected waterborne protozoa mentioned above and provides future perspectives.


Antioxidant strategies in the treatment of stroke.
Excessive production of free radicals is known to lead to cell injury in a variety of diseases, such as cerebral ischemia. In this review, we describe some of the numerous studies that have examined this oxidative stress and the efficiency of antioxidant strategies in focal cerebral ischemia. Besides using genetically modified mice, these strategies can be divided into three groups: (1) inhibition of free radical production, (2) scavenging of free radicals, and (3) increase of free radical degradation by using agents mimicking the enzymatic activity of endogenous antioxidants. Finally, the clinical trials that have tested or are currently testing the efficiency of antioxidants in patients suffering from stroke are reviewed. The results presented here lead us to consider that antioxidants are very promising drugs for the treatment of ischemic stroke.


Pediatric headache and neuroimaging: experience of two tertiary centers.
Headache is a frequent complaint in children and adolescents. Decision-making for neuroimaging should take into account the cost and the need for sedation in young children. To evaluate the yield of MRI in pediatric headache patients seen in two large tertiary hospitals. Data were retrospectively collected from patient records (n = 613) and neuroimaging reports. Headache was classified according to International Headache Society guidelines. There were 346 children with imaging studies (MRI n = 281, CT n = 65). Of patients who had at least one MRI study, 29% demonstrated an abnormal finding. Findings altering the management were obtained in 21 (7%) patients: the majority (n = 17, 80%) had headache for less than 3 months. On the other hand, four patients with headache longer than 3 months (19%) and 12 patients with normal neurological examination (57%) had significant MRI results affecting management. None of the children in whom the diagnosis of migraine could be made on clinical grounds (n = 40) had a significant MRI finding. Neuroimaging should be performed selectively in children with headache seen in pediatric neurology clinics, especially in headache of short duration (< 3 months) and features atypical for migraine. A normal neurological examination should not reassure the clinician.


CT-ultrasound fusion prostate brachytherapy: a dynamic dosimetry feedback and improvement method. A report of 54 consecutive cases.
The authors describe a prostate brachytherapy technique with dynamic dosimetry feedback, using coregistered CT and ultrasound (US) images, to map initial dosimetry deficiencies and guide remedial source placement. Fifty-four consecutive patients treated with this method were analyzed for coregistration accuracy and dosimetry outcomes by evaluating the prostate V100, V150, D90, and urethral D50 and D10. Dosimetric improvements created by remedial source placement and preplan/postplan prostate D90 agreement were evaluated. Median CT-US coregistration discrepancy with this technique ranged from 0 to 4mm, with the posterior midline prostate and base prostate providing the least consistent and the urethra providing the most consistent coregistration agreement. Final prostate V100 values ranged from 96.1% to 99.8% for all patients. The addition of remedial sources directed by CT-US fusion produced V100 and D90 improvements whose magnitude inversely correlated with the initial result and exceeded the effect of adding quantitatively identical randomly distributed increased millicuries. The final prostate D90 result agreed within (-) 5% to (+) 10% of the preplan result in 98% of all patients. CT-US fusion prostate brachytherapy represents a dynamic dosimetry feedback and remediation method that consistently produced high prostate V100 and D90 values with acceptably low urethra D50 and D10 values in our study. The degree of prostate V100 and D90 dosimetry improvement created by remedial source placement effectively matched the degree of initial dosimetry deficiency. This method produced a high level of correlation between the preplan and final prostate D90 values.


Efficacy of cancer vaccines in selected gynaecological breast and ovarian cancers: A 20-year systematic review and meta-analysis.
Therapeutic cancer vaccination is an area of interest, even though promising efficacy has not been demonstrated so far. A systematic review and meta-analysis was conducted to evaluate vaccines' efficacy on breast cancer (BC) and ovarian cancer (OC) patients. Our search was based on the PubMed electronic database, from 1st January 2000 to 4th February 2020. response rate (ORR) was the primary end-point of interest, while progression-free survival (PFS), overall survival (OS) and toxicity were secondary end-points. Analysis was performed separately for BC and OC patients. Pooled ORRs were estimated by fixed or random effects models, depending on the detected degree of heterogeneity, for all studies with more than five patients. Subgroup analyses by vaccine type and treatment schema as well as sensitivity analyses, were implemented. Among 315 articles initially identified, 67 were eligible for our meta-analysis (BC: 46, 1698 patients; OC: 32, 426 patients; where both BC/OC in 11). Dendritic-cell and peptide vaccines were found in more studies, 6/10 BC and 10/13 OC studies, respectively. In our primary BC analysis (21 studies; 428 patients), the pooled ORR estimate was 9% (95%CI[5%,13%]). The primary OC analysis (12 studies; 182 patients), yielded pooled ORR estimate of 4% (95%CI[1%,7%]). Similar were the results derived in sensitivity analyses. No statistically significant differences were detected by vaccine type or treatment schema. Median PFS was 2.6 months (95% confidence interval (CI)[1.9,2.9]) and 13.0 months (95%CI[8.5,16.3]) for BC and OC respectively, while corresponding median OS was 24.8 months (95%CI[15.0,46.0]) and 39.0 months (95%CI[31.0,49.0]). In almost all cases, the observed toxicity was only moderate. Despite their modest results in terms of ORR, therapeutic vaccines in the last 20 years display relatively long survival rates and low toxicity. Since a plethora of different approaches have been tested, a better understanding of the underlying mechanisms is needed in order to further improve vaccine efficacy.


Environmental Se-Mo-B deficiency and its possible effects on crops and Keshan-Beck disease (KBD) in the Chousang area, Yao County, Shaanxi Province, China.
Causes of Keshan-Beck disease (KBD) are still being probed and monitored in China. Relationships between trace elements from eco-environmental systems and KBD are poorly understood although relationships between environmental Se and human health have received extensive attention. In order to investigate relationships between eco-environmental geochemistry and KBD, we selected the Chousang KBD area in Yao County, Shaanxi Province, China, as an example of a prevailing KBD area applying I-Se-rich salts instead of utilizing Se-rich fertilisers on food crops to prevent local residents from developing KBD before 1995. Environmentally geochemical samples (rocks, soils, plants and children's hair) were collected from the Chousang KBD area. Soils in the study area contain 0.11 +/- 0.02 microgram Se g-1, 0.75 +/- 0.11 microgram Mo g-1, and 34.5 +/- 1.5 micrograms B g-1 on average, indicating that the study area is a deficient-Se-Mo-B area. Se (0.07 +/- 0.007 microgram g-1), Mo (0.35 +/- 0.09 microgram g-1) and B (3 +/- 0 micrograms g-1) contents are low in wheat and corn used as a daily main food staple of local inhabitants. It is indicated that the study area is deficient in environmental Se-Mo-B for the local residents. Se contents of children's hair from the Yangyuan Elementary School in the study area range from 0.09 to 0.26 microgram Se g-1 with an average of 0.165 +/- 0.05 microgram Se g-1 (n = 10) in this KBD endemic area. Due to the low levels of Se, Mo and B available in soils and rocks, crops including wheat and corn are deficient in these elements, accordingly, the deficiency of Se, Mo and B in this area may be linked to the daily consumption of wheat and corn deficient in Se, Mo and B. Therefore, local inhabitants should be encouraged to fertilise mixtures of Se, Mo and B on crop plants in order to avoid development of KBD and guarantee a good harvest of crops.


Global abundance of short tandem repeats is non-random in rodents and primates.
While of predominant abundance across vertebrate genomes and significant biological implications, the relevance of short tandem repeats (STRs) (also known as microsatellites) to speciation remains largely elusive and attributed to random coincidence for the most part. Here we collected data on the whole-genome abundance of mono-, di-, and trinucleotide STRs in nine species, encompassing rodents and primates, including rat, mouse, olive baboon, gelada, macaque, gorilla, chimpanzee, bonobo, and human. The collected data were used to analyze hierarchical clustering of the STR abundances in the selected species. We found massive differential STR abundances between the rodent and primate orders. In addition, while numerous STRs had random abundance across the nine selected species, the global abundance conformed to three consistent < clusters>, as follows: <rat, mouse>, <gelada, macaque, olive baboon>, and <gorilla, chimpanzee, bonobo, human>, which coincided with the phylogenetic distances of the selected species (p < 4E-05). Exceptionally, in the trinucleotide STR compartment, human was significantly distant from all other species. Based on hierarchical clustering, we propose that the global abundance of STRs is non-random in rodents and primates, and probably had a determining impact on the speciation of the two orders. We also propose the STRs and STR lengths, which predominantly conformed to the phylogeny of the selected species, exemplified by (t)10, (ct)6, and (taa4). Phylogenetic and experimental platforms are warranted to further examine the observed patterns and the biological mechanisms associated with those STRs.


A long-term 0.01° surface air temperature dataset of Tibetan Plateau.
The surface air temperature (Ta) dataset of the Tibetan Plateau is obtained by downscaling the China regional surface meteorological feature dataset (CRSMFD). It contains the daily mean Ta and 3-hourly instantaneous Ta. This dataset has a spatial resolution of 0.01°. Its time range for surface air temperature dataset is from 2000 to 2015. Spatial dimension of data: 73°E-106°E, 40°N-23°N. The Ta with a 0.01° can serve as an important input for the modeling of land surface processes, such as surface evapotranspiration estimation, agricultural monitoring, and climate change analysis.


Investigating quality of life and coping resources after laryngectomy.
Surgical procedures and in particular laryngectomy can become a life-saving treatment for patients with laryngeal or hypopharyngeal cancer, but can result in permanent damage. Clinical observation suggests that patients vary considerably in their ways of dealing with this new situation and in their ability to cope. The aim of our interdisciplinary group was to investigate the quality of life of laryngectomy patients and learn about their perceptions, situation and coping mechanisms. The development of an appropriate study design and a measurement strategy is presented. We investigated 29 laryngectomized patients who had joined the local self-help group. The patients were free from tumour disease and were mostly married with children, retired from work and had not graduated from high school. Assessment of the quality of life was performed with the European Organization for Research on Treatment of Cancer questionnaires QLQ-C30 and H+N35 and additional open questions. Analysis of the acquired data showed that family support was judged most important for overcoming the problems of disease and treatment. Deficits in this area were highly correlated with a low overall quality of life. Financial problems resulted because of the high percentage of retirement before or after therapy. We suggest that perioperative support taking these facts into consideration can result in an improved coping process. Further prospective studies are needed to reveal the effect of such measures.


A highly selective purine-based inhibitor of CSF1R potently inhibits osteoclast differentiation.
The colony-stimulating factor 1 receptor (CSF1R) plays an important role in the regulation of many inflammatory processes, and overexpression of the kinase is implicated in several disease states. Identifying selective, small-molecule inhibitors of CSF1R may be a crucial step toward treating these disorders. Through modelling, synthesis, and a systematic structure-activity relationship study, we have identified a number of potent and highly selective purine-based inhibitors of CSF1R. The optimized 6,8-disubstituted antagonist, compound 9, has enzymatic IC50 of 0.2 nM, and displays a strong affinity toward the autoinhibited form of CSF1R, contrasting that of other previously reported inhibitors. As a result of its binding mode, the inhibitor shows excellent selectivity (Selectivity score: 0.06), evidenced by profiling towards a panel of 468 kinases. In cell-based assays, this inhibitor shows dose-dependent blockade of CSF1-mediated downstream signalling in murine bone marrow-derived macrophages (IC50 = 106 nM) as well as disruption of osteoclast differentiation at nanomolar levels. In vivo experiments, however, indicate that improve metabolic stability is needed in order to further progress this compound class.


MM 42842, a new member of the monobactam family produced by Pseudomonas cocovenenans. II. Production, isolation and properties of MM 42842.
A new member of the monobactam family of beta-lactam antibiotics, designated MM 42842, has been detected in a culture of Pseudomonas cocovenenans. The production, isolation and some properties of the antibiotic are described. Structural studies show MM 42842 to be closely related to the previously described antibiotic sulfazecin.


Prevalence of transthyretin cardiac amyloidosis in elderly patients diagnosed with heart failure.
There is increased interest in studying ATTR-CA, a pathology that primarily affects patients of geriatric age and is frequently underdiagnosed. We aim to establish the prevalence of ATTR-CA in a cohort of patients with a history of HFpEF and to describe its characteristics. We conducted a prospective observational study. Patients ≥75 years, clinical history of HFpEF, atrial dilation ≥34ml/m2 and left ventricular wall thickening >13mm, were included. Demographic and analytical parameters were collected, and a comprehensive geriatric assessment was performed, along with a transthoracic echocardiogram and cardiac scintigraphy. Finally, telephone follow-up was carried out at 6 and 12 months. 50 patients were recruited, mean age 86±6 years, 54% women. Age and functional class (I-II vs. III-IV) were factors associated with presenting with ATTR-CA. Patients with positive scintigraphy had a median time to admission of 5.2 months (confidence interval [CI] 95% 0-10.9), while in those with negative scintigraphy, it was 12.2 months (95% CI 11.7-12.8); log-rank: p=0.064. Patients with positive scintigraphy had a median time to the combined endpoint (death and readmission) of 1.9 months (95% CI 0-6.1), and patients with negative scintigraphy of 11.9 months (95% CI 11.7-12); log-rank: p=0.027. ATTR-CA appears to be a prevalent etiology in elderly patients within the spectrum of HFpEF. Patients with a diagnosis of ATTR-CA had a shorter time to admission for HF and the combined event of death and admission than patients with a negative result on scintigraphy.


Microspheres for biomedical applications: preparation of reactive and labelled microspheres.
This review describes the synthesis and physico-chemical properties of reactive and labelled microspheres useful for biomedical applications. Preparation of microspheres with specific functional groups, fluorescent species, radionuclides and magnetite particles (Fe2O3) are discussed. Physico-chemical properties of microspheres, including surface charge and hydrophilicity/hydrophobicity, are also briefly covered.


Disinfection of surfaces by photocatalytic oxidation with titanium dioxide and UVA light.
Particularly in microbiological laboratories and areas in intensive medical use, regular and thorough disinfection of surfaces is required in order to reduce the numbers of bacteria and to prevent bacterial transmission. The conventional methods of disinfection with wiping are not effective in the longer term, cannot be standardized, are time- and staff-intensive and use aggressive chemicals. Disinfection with hard ultraviolet C (UVC) light is usually not satisfactory, as the depth of penetration is inadequate and there are occupational medicine risks. Photocatalytic oxidation on surfaces coated with titanium dioxide (TiO2) might offer a possible alternative. In the presence of water and oxygen, highly reactive OH-radicals are generated by TiO2 and mild ultraviolet A (UVA). These radicals are able to destroy bacteria, and may therefore be effective in reducing bacterial contamination. Direct irradiation with UVC however can produce areas of shadow in which bacteria are not inactivated. Using targeted light guidance and a light-guiding sheet (out of a UVA-transmittant, Plexiglas, for example), as in the method described in the present study, bacterial inactivation over the entire area is possible. The effectiveness of the method was demonstrated using bacteria relevant to hygiene such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecium. For these bacteria, a reduction efficiency (RE) more than 6log10 steps in 60 min was observed. Using Candida albicans, a RE of 2log10 steps in 60 min was seen. Light and scanning electron microscopic examinations suggest that the germ destruction achieved takes place through direct damage to cell walls caused by OH-radicals.


Analysis of sequence-similar pentapeptides in unrelated protein tertiary structures. Strategies for protein folding and a guide for site-directed mutagenesis.
From the most recent Brookhaven Protein Co-ordinate Databank, 229 sequence-identical pentapeptide pairs, each found in two unrelated protein structures, were collected; 9115 such pairs differing in only one residue were also gathered. For both samples the main-chain fold was conserved about 20% of the time, despite the different atomic environments presented by the unrelated protein architectures. An analysis of the substituted residues as well as the composition of the sequence-similar pentapeptides allowed several suggestions regarding protein folding mechanisms. An examination of the most frequently observed residue substitutions and their correlation with structural changes in the oligopeptide pairs yields a possible guide for site-directed mutagenesis experiments, especially when no tertiary structural information is at hand.


Engaging medical physics students in active and authentic learning through the use of monte-carlo simulation and inverse treatment planning.
Engagement and participation of students with the learning process has been recognised as a growing problem across the higher education sector. The aim of this study was to investigate the value and impact of introducing Problem-based Learning (PBL) activities into a radiotherapy physics unit of a postgraduate medical physics course. Computer-based problem solving activities on 1) monte-carlo modelling of a linear accelerator and 2) inverse radiotherapy treatment planning were designed and implemented into a one-semester unit on radiotherapy physics. The value and impact of the activities on the student learning were evaluated through student surveys, a focus group, and peer observation of the sessions by members of the learning design team. Student attendance and grade profile data are also reported. Overall the results indicated that students had a positive experience with the new problem solving activities that were implemented. Survey responses from a number of students indicated a desire for increased theoretical and technical support prior to and during activities. Another underlying theme that emerged from survey and focus group response was the perceived lack of reward in terms of marks for their efforts working on the learning activities. This may have influenced students' choices around attendance and participation. No significant changes were noted in the overall grades achieved in the unit. Students appreciated the more hands-on approach to learning in the form of more authentic activities that they could directly relate to clinical radiotherapy. Further work is required to update and integrate assessment into the new learning delivery model more directly.


Pollen wall and tapetal development in Cymbalaria muralis: the role of physical processes, evidenced by in vitro modelling.
Our aim was to unravel the underlying mechanisms of pollen wall development in Cymbalaria muralis. By determining the sequence of developing substructures with TEM, we intended to compare it with that of other taxa and clarify whether physical processes of self-assembly and phase separation were involved. In parallel, we tried to simulate in vitro the substructures observed in Cymbalaria muralis exine development, using colloidal mixtures, to determine whether purely physical self-assembly processes could replicate them. Exine ontogeny followed the main stages observed in many other species and was initiated by phase separation, resulting in heterogeneity of the homogeneous contents of the periplasmic space around the microspore which is filled with genome-determined substances. At every stage, phase separation and self-assembly come into force, gradually driving the substances through the sequence of mesophases: spherical micelles, columns of spherical micelles, cylindrical micelles arranged in a layer, laminate micelles. The final two of these mesophases define the structure of the columellate ectexine and lamellate endexine respectively. Structures obtained in vitro from colloidal mixtures simulated the developing exine structures. Striking columella-like surface of some abnormal tapetal cells and lamella-like structures in the anther medium confirm the conclusion that pattern generation is a feature of colloidal materials, after genomic control on material contents. Simulation experiments show the high pattern-generating capacity of colloidal interactions.


Fat tissue and inflammation in patients undergoing peritoneal dialysis.
Body weight has been increasing in the general population and is an established risk factor for hypertension, diabetes, and all-cause and cardiovascular mortality. Patients undergoing peritoneal dialysis (PD) gain weight, mainly during the first months of treatment. The aim of this study was to assess the relationship between body composition and metabolic and inflammatory status in patients undergoing PD. This was a prospective, non-interventional study of prevalent patients receiving PD. Body composition was studied every 3 months using bioelectrical impedance (BCM(®)). We performed linear regression for each patient, including all BCM(®) measurements, to calculate annual changes in body composition. Thirty-one patients in our PD unit met the inclusion criteria. Median follow-up was 26 (range 17-27) months. Mean increase in weight was 1.8 ± 2.8 kg/year. However, BCM(®) analysis revealed a mean increase in fat mass of 3.0 ± 3.2 kg/year with a loss of lean mass of 2.3 ± 4.1 kg/year during follow-up. The increase in fat mass was associated with the conicity index, suggesting that increases in fat mass are based mainly on abdominal adipose tissue. Changes in fat mass were directly associated with inflammation parameters such as C-reactive protein (r = 0.382, P = 0.045) and inversely associated with high-density lipoprotein cholesterol (r=-0.50, P = 0.008). Follow-up of weight and body mass index can underestimate the fat mass increase and miss lean mass loss. The increase in fat mass is associated with proinflammatory state and alteration in lipid profile.


Critical review on uranium and arsenic content and their chemical mobilization in groundwater: A case study of the Malwa region Punjab, India.
The presence of pollutants like uranium and arsenic in the groundwater can have a terrible impact on people's health (both radiologically and toxicologically) and their economic conditions. Their infiltration into groundwater can occur through geochemical reactions, natural mineral deposits, mining and ore processing. Governments and scientists are working to address these issues, and significant progress has been achieved, but it's challenging to deal with and mitigate without adequately understanding the different chemical processes and the mobilization mechanism of these hazardous chemicals. Most of the articles and reviews have focused on the particular form of contaminants and specific sources of pollution, such as fertilizers. However, no literature report exists explaining why particular forms appear and the possible basis of their chemical origins. Hence, in this review, we tried to answer the various questions by devising a hypothetical model and chemical schematic flowcharts for the chemical mobilization of arsenic and uranium in groundwater. An effort has been made to explain how chemical seepage and excessive groundwater use resulted in the change in aquifers' chemistry, as evidenced by their physicochemical parameters and heavy metal analysis. Many technological advancements have taken place to mitigate these issues. Still, in low-middle-income countries, especially in the Malwa region of Punjab, also known as Punjab's cancer belt, paying a high amount for installing and maintaining these technologies is an unviable option. In addition to working to improve people's access to sanitary facilities and clean water to drink, the policy-level intervention would focus on increasing community awareness and continued research on developing better and more economical technologies. Our designed model/chemical flowcharts will help policymakers and researchers better understand the problems and alleviate their effects. Moreover, these models can be utilized in other parts of the globe where similar questions exist. This article emphasises the value of understanding the intricate issue of groundwater management through a multidisciplinary and interdepartmental approach.


Modulation of reflex responses during fictive locomotion in the forelimb of the cat.
During cat forelimb fictive locomotion, short-latency reflex pathways were examined by recording nerve discharges and intracellularly from motoneurones. Stimulation of cutaneous afferents, superficial radial nerves, evoked trisynaptic excitation of the elbow flexors, biceps brachii and brachialis, and stimulation of muscle afferents, deep radial nerves, evoked oligosynaptic, i.e. monosynaptic and disynaptic excitation of the flexors. The short-latency excitatory postsynaptic potentials (EPSPs) evoked from both nerves were rhythmically modulated; they were facilitated during the flexion phase and suppressed during the extension phase. Stimulation of high threshold muscle afferents evoked EPSPs with a central delay of ca. 4.2 ms, which were depressed throughout episodes of fictive locomotion. Since the short-latency EPSPs and longer-latency EPSPs in the same motoneurone were differently influenced during fictive locomotion, the effects observed could not be explained by changes occurring at only the motoneuronal level but they probably occurred at the premotoneuronal level. In addition, short-latency cutaneous excitation of the distal muscles, innervated by the median and ulnar nerves, was little modulated during fictive locomotion.


Lipocortin-1 (annexin-1) suppresses activation of autoimmune T cell lines in the Lewis rat.
Increased levels of lipocortins occur in the nervous system in multiple sclerosis, in experimental autoimmune encephalomyelitis and experimental neuritis at the height of disease and decrease thereafter, suggesting their potential involvement in recovery from disease. We therefore investigated whether lipocortins may suppress activation of autoimmune T cells. Antigen-specific and growth factor-mediated proliferation of T cell lines reactive with myelin basic protein (MBP) was measured in the presence of recombinant lipocortin-1, -2, and -5, and natural bovine lipocortin-1 using various concentrations and incubation periods. We also employed an N-terminal lipocortin-1 peptide spanning aa 1-26, a proteolytic fragment of lipocortin-1 where the respective N-terminal region was clipped off, tested blocking with a neutralizing antibody, and investigated the effect of alkaline phosphatase treatment. Both human recombinant and bovine lipocortin-1 had a marked suppressive effect on T cell activation by MBP and the respective immunogenic peptide. When added at 3 micrograms/ml we observed up to 90% inhibition of T cell proliferation between day 2 and 3, but not at earlier time points of activation. The inhibitory effect of human lipocortin-1 was blocked after addition of a neutralizing antibody directed against lipocortin-1. Lipocortin-2 and -5, and the N-terminal peptide of lipocortin-1 were ineffective, whereas the fragment spanning residues 27-345 of lipocortin-1 retained full activity. Treatment of bovine lipocortin-1 with alkaline phosphatase did not alter immunosuppressive properties.


Cross-sectional exploration of brain functional connectivity in the triadic development model of adolescents.
Adolescence represents a transitional stage with increased risk taking and mood dysregulation. These vulnerabilities are accountable by developmental dynamics in the triadic functional brain networks underlying reward seeking (REW), emotional avoidance (EMO), and cognitive regulation (COG). However, these triadic dynamics, though conceptually established, have yet been investigated directly. Capitalizing on public database of resting-state fMRI from 222 adolescents (8-18 years old, 89F133M), this study examined cross-sectional development profiles of functional connectivity (FC) by jointly considering bilateral seeds of the ventral striatum, amygdala, and dorsal lateral prefrontal cortex in probing the networks of REW, EMO, and COG, respectively. Positive and negative FCs were considered separately for clarification of synergetic and suppressive interactions. While the REW and EMO mostly exhibited quadratic FC changes across age, suggesting reduced reward sensitivity and risk avoidance, the COG exhibited both linear and quadratic FC changes, suggesting both protracted maturation of cognitive ability and lowered top-down regulation. Additional age × gender effects were identified in the precentral gyrus and superior medial prefrontal cortex, which may associate risky action and emotion dysregulation to boys and girls, respectively. These results provide network evidence in substantiating the "triadic model" and deepening existing insights into neurodevelopmental mechanisms associated with adolescent behavior.