Successful aging in individuals with schizophrenia dwelling in the community: a study on attitudes toward aging and preparing behavior for old age.
'Successful aging' in individuals with schizophrenia has been attracting attention. We examined two forward-looking factors of successful aging among schizophrenia patients: 'attitude toward aging' and 'preparing behavior for old age'. Fifty-seven middle-aged and elderly schizophrenia patients with successful aging were identified using the Attitude toward Aging Scale, the Preparing Behavior for Old Age Scale, and assessments of their cognitive function, psychiatric symptoms, social functioning and quality of life. A multiple regression analysis was used to detect determinants of attitude toward aging/preparing behavior for old age at that time ('present': community dwelling). We also analyzed predictors of successful aging using demographic/clinical data assessed 3 years previously ('past': residential care). The multiple regression analysis revealed that quality of life was a significant determinant: a higher quality of life was related to a more positive attitude toward aging and less active preparing behavior. The significant predictors of preparing behavior were quality of life and the length of the hospital stay: a longer hospital stay and a higher quality of life were related to less active preparing behavior. Quality of life and the length of the hospital stay significantly contributed to forward-looking factors of successful aging. Avoiding long hospitalization periods for patients with schizophrenia may lead to more active preparing behavior, but the improvement of quality of life may not be a sufficient condition. As schizophrenia patients have an optimistic attitude and insufficient preparing behavior, support to prepare such individuals for old age is required as part of community-based psychiatric care strategies.


Hereditary ATTR amyloidosis: burden of illness and diagnostic challenges.
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease characterized by deposition of amyloid fibrils in various organs and tissues of the body. There are a wide variety of clinical presentations for this multisystemic disorder, so it is often misdiagnosed or subject to delayed diagnosis. Although the exact prevalence is difficult to determine, existing estimates suggest a worldwide prevalence of 50,000 individuals, with varying phenotypic presentations of disease. Due to the heterogeneous nature of its presentation, incorrect or delayed diagnosis can severely impact quality of life for these patients. hATTR amyloidosis can lead to significant disability and mortality. After an accurate diagnosis of hATTR amyloidosis is established, new patients should undergo appropriate therapy as soon as possible. Current treatment options for hATTR amyloidosis are limited, but orthotopic liver transplant serves as an established option for patients with early-stage disease. Consequently, there is a need for new, effective, and safe therapies.


Molecular Characterization and Seroprevalence in Pigs of SC0806, a Cat Que Virus Isolated from Mosquitoes in Sichuan Province, China.
The Simbu serogroup currently consists of a highly diverse group of related arboviruses that infect both humans and economically important livestock species. Cat Que virus (CQV), a Simbu serogroup virus of the genus Orthobunyavirus (family Bunyaviridae), was first isolated in 2004 from mosquitoes during surveillance of arbovirus activity in acute pediatric encephalitis in northern Vietnam. We report here the complete genome sequence of SC0806 isolated from mosquitoes (Culex tritaeniorhynchus) in Sichuan Province, China. Consistent with the genomic organization of Simbu serogroup viruses, the SC0806 genome comprises three RNA segments-a large (L) segment (6928 nucleotides) that encodes the 2261-amino-acid RNA-dependent RNA polymerase, a medium (M) segment (4481 nucleotides) that encodes the 1433-amino-acid polyprotein, and a small (S) segment (984 nucleotides) that encodes a 234-amino-acid nucleocapsid protein and a 95-amino-acid nonstructural protein. The respective lengths of the 5'-untranslated region (UTR) and 3'-UTR of L, M, and S are 56 and 86, 43 and 136, and 44 and 238 nucleotides. Sequence (nucleotide and deduced amino acid) comparison and phylogenetic analysis revealed that SC0806 was closely related to the reported Vietnam isolate CQV. This is the first time that CQV has been isolated in Sichuan Province, China. Anti-SC0806 immunoglobulin M (IgM) and IgG antibodies were found in pigs reared locally, indicating that CQV has formed a natural cycle in the local area. Surveillance of the distribution and pathogenicity of SC0806 should be strengthened.


Impact of respiratory motion correction and spatial resolution on lesion detection in PET: a simulation study based on real MR dynamic data.
The aim of this study is to investigate the impact of respiratory motion correction and spatial resolution on lesion detectability in PET as a function of lesion size and tracer uptake. Real respiratory signals describing different breathing types are combined with a motion model formed from real dynamic MR data to simulate multiple dynamic PET datasets acquired from a continuously moving subject. Lung and liver lesions were simulated with diameters ranging from 6 to 12 mm and lesion to background ratio ranging from 3:1 to 6:1. Projection data for 6 and 3 mm PET scanner resolution were generated using analytic simulations and reconstructed without and with motion correction. Motion correction was achieved using motion compensated image reconstruction. The detectability performance was quantified by a receiver operating characteristic (ROC) analysis obtained using a channelized Hotelling observer and the area under the ROC curve (AUC) was calculated as the figure of merit. The results indicate that respiratory motion limits the detectability of lung and liver lesions, depending on the variation of the breathing cycle length and amplitude. Patients with large quiescent periods had a greater AUC than patients with regular breathing cycles and patients with long-term variability in respiratory cycle or higher motion amplitude. In addition, small (less than 10 mm diameter) or low contrast (3:1) lesions showed the greatest improvement in AUC as a result of applying motion correction. In particular, after applying motion correction the AUC is improved by up to 42% with current PET resolution (i.e. 6 mm) and up to 51% for higher PET resolution (i.e. 3 mm). Finally, the benefit of increasing the scanner resolution is small unless motion correction is applied. This investigation indicates high impact of respiratory motion correction on lesion detectability in PET and highlights the importance of motion correction in order to benefit from the increased resolution of future PET scanners.


A phase II study of liposomal doxorubicin in recurrent epithelial ovarian carcinoma.
We conducted a phase II trial to evaluate the efficacy and safety of liposomal formulation of doxorubicin in recurrent ovarian carcinoma patients. Thirty patients were included in the study after having obtained an informed consent. Their main characteristics were: median age, 64 years (range, 45-80), ECOG performance status 0 in 17 patients (56%), 1 in 11 patients (36%) and 2 in 2 patients (6.6%). Eighteen patients had metastatic disease and 12 locally advanced disease. All patients were pretreated with a platinum-based chemotherapy: 3 were considered refractory to platinum (progression or stable disease), 2 were platinum resistant (relapse < 12 months), and 7 were platinum sensitive (relapse > or = 12 months). Treatment consisted of liposomal doxorubicin, 50 mg/m2 every 4 weeks. The overall response rate was 26.6%, with 2 complete responses and 6 partial responses lasting 3.5 months. The incidence of grade 3-4 toxicity was 23.3% for neutropenia, 10% for mucositis and 10% for plantar-palmar erythrodysesthesia. Median survival was 12+ months (range, 2-26+). Liposomal doxorubicin appears to be a moderately active drug in pretreated patients, and its activity seems to be similar to that reported for other active regimens in terms of response rate. The toxicological profile of liposomal doxorubicin suggests that it may be combined with other drugs in the treatment of patients with ovarian cancer.


Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice.
A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.


The role of menopausal hormone therapy in women with or at risk of ovarian and breast cancers: Misconceptions and current directions.
For women who are candidates for menopausal hormone therapy (MHT), estrogen can provide relief from symptomatic menopause, decrease rates of chronic illnesses, and improve health-related quality of life. However, confusion surrounds the evidence regarding the impact of exogenous estrogen and progesterone on the breast and ovary. Available data regarding the risks of MHT (estrogen and/or progestin) related to the development of breast and ovarian cancer are often inconsistent or incomplete. Modern molecular and genetic techniques have improved our understanding of the heterogeneity of breast and ovarian cancer. This enhanced understanding of the disease has impacted our understanding of carcinogenesis. Treatment options have evolved to be more targeted toward hormonal therapy for certain subtypes of disease, whereas cytotoxic chemotherapy remains the standard for other histological and molecular subtypes. The role of MHT in the breast and ovarian cancer survivor, as well as women who are at high risk for the development of hereditary breast and ovarian cancer, remains controversial despite evidence that this treatment can improve quality of life and survival outcomes. Through this article, we examine the evidence for and against the use of MHT with a focus on women who have or are at high risk for breast and ovarian cancer.


Hair Cortisol, Testosterone, Dehydroepiandrosterone Sulfate and Their Ratios in Stallions as a Retrospective Measure of Hypothalamic-Pituitary-Adrenal and Hypothalamic-Pituitary-Gonadal Axes Activity: Exploring the Influence of Seasonality.
The monitoring of stress physiology includes studying a wide range of endocrinological mechanisms, which can be assessed using multiple tissue samples. This study aimed to evaluate the seasonal variations of hair C, T and DHEA-S in horses for a whole year, as well as to assess the variations between seasons of C/DHEA-S and T/C ratios as a retrospective measure of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axis activity. Ten pure-breed Menorca stallions were included in the study. The hair samples were collected approximately every two months following the shave-reshave method caudally to the sternum. After a methanol-based extraction, samples were analyzed by enzyme immunoassay for cortisol, testosterone, and dehydroepiandrosterone sulphate. Following our findings, we detected that cortisol, testosterone and dehydroepiandrosterone sulphate were significantly affected by seasonality, with the highest values of cortisol during summer and the lowest values of testosterone during spring. Dehydroepiandrosterone sulphate concentrations were increased in autumn compared to the other studied periods. Additionally, the studied hormone ratios showed variations between seasons. To conclude, season should, therefore, be considered when assessing sexual and stress hormones in stallion hair, since this variable can be a potential influencing factor and led to misinterpretations.


Role of antiviral antibodies in resistance against coxsackievirus B3 infection: interaction between preexisting antibodies and an interferon inducer.
An experimental model of coxsackievirus B3 infection in newborn mice was utilized to examine the protective role of antiviral antibodies and an interferon inducer, polyinosinic acid-polycytidylic acid [poly(I:C)]. Subcutaneous administration to the infected mice of specific antiviral antibodies resulted in significant protection against coxsackievirus B3 infection. Antibody-treated animals had shortened viremia, early clearance of virus from tissues, and a reduced mortality rate. Dose response to antibodies was clearly demonstrated. However, the time of antibody administration in relation to the infection cycle was important. The protection was observed if antibodies were given before infection (24 h) or shortly after (2 h) infection. Administration of antibodies 24 h after infection resulted in no protection. The interferon inducer poly(I:C) prolonged the survival time of the infected mice, but this protective effect was incomplete and could only be demonstrated in animals treated before infection (24 h) or shortly after (2 h) infection. Enhanced protection against lethal coxsackievirus B3 infection was achieved in animals treated with a combination of antiviral antibodies and poly(I:C). These data confirm that antibody-mediated immunity plays a significant role in resistance against coxsackievirus B3 infection and suggest that antiviral antibodies may interact with poly(I:C) or work independently to produce an enhanced protective effect.


Comparison of genetic diversity between Canadian adapted genotypes and exotic germplasm of soybean.
Soybean (Glycine max (L.) Merr.) was domesticated in China and the greatest genetic diversity for this species is found in Asia. In contrast, in North America, soybean cultivars trace back to a small number of plant introductions from Asia and genetic diversity is typically quite limited. The purpose of this work was to measure and compare the genetic diversity in two sets of soybean lines. The first set (termed "local") was composed of 100 lines used in a private breeding program in Quebec. The second set (termed "exotic") was composed of 200 lines from elsewhere in the world (but mostly from Asia) and included a few lines of Glycine soja, the wild progenitor of cultivated soybean. Almost all the genotypes belonged to maturity groups between 000 and II. A total of 39 microsatellites (SSRs) were used to genotype the two collections. The number of alleles per locus was almost twice as great in the exotic set compared with the local set. Also, the number of "unique" alleles, i.e., those uniquely present in one set and absent in the other, was almost fivefold greater (191 vs. 37) in a subset of 108 exotic lines with good adaptation than among the local set. A genetic distance matrix, a UPGMA cluster analysis, and a principal coordinate analysis were conducted based on the SSR data. These analyses all indicated that the exotic set was much more diverse and formed a clearly distinct group from the local set. Interestingly, some of the lines showing the best adaptation to local conditions were quite distinctive in terms of their genotype and could potentially contribute useful novel genetic variation within the breeding program.


Trafficking and secretion of matrix metalloproteinase-2 in olfactory ensheathing glial cells: A role in cell migration?
Olfactory ensheathing cells (OECs) are unique glia found only in the olfactory system. They retain exceptional plasticity and support olfactory neurogenesis and retargeting across the PNS:CNS boundary in the olfactory system. OECs have been shown to improve functional outcome when transplanted into rodents with spinal cord injury. The growth-promoting properties of implanted OECs encompass their ability to migrate through the scar tissue and render it more permissive for axonal outgrowth, but the underlying molecular mechanisms remain poorly understood. OECs appear to regulate molecules of the extracellular matrix (ECM) that inhibit axonal growth. Among the proteins that have the potential to promote cell migration, axonal regeneration and remodeling of the ECM are matrix metalloproteinases (MMPs), a family of endopeptidases that cleave matrix, soluble, and membrane-bound proteins and that are regulated by their endogenous inhibitors, the tissue inhibitors of MMPs (TIMPs). Little is known about MMP/TIMP trafficking, secretion, and role in OECs. Using a combination of cell biology, biochemistry, pharmacology, and imaging techniques, we show that MMP-2 and MMP-9 are expressed and proteolytically active in the olfactory epithelium and in particular in the OECs of the lamina propria. These proteinases and regulatory proteins such as MT1-MMP and TIMP-2 are expressed in cultured OECs. MMPs exhibit nuclear localization and vesicular trafficking and secretion, with distribution along microtubules and microfilaments and co-localization with the molecular motor protein kinesin. Finally, we show that MMPs are involved in migration of OECs in vitro on different ECM substrates.


Evaluating participant responses to a virtual reality experience using reinforcement learning.
Virtual reality applications depend on multiple factors, for example, quality of rendering, responsiveness, and interfaces. In order to evaluate the relative contributions of different factors to quality of experience, post-exposure questionnaires are typically used. Questionnaires are problematic as the questions can frame how participants think about their experience and cannot easily take account of non-additivity among the various factors. Traditional experimental design can incorporate non-additivity but with a large factorial design table beyond two factors. Here, we extend a previous method by introducing a reinforcement learning (RL) agent that proposes possible changes to factor levels during the exposure and requires the participant to either accept these or not. Eventually, the RL converges on a policy where no further proposed changes are accepted. An experiment was carried out with 20 participants where four binary factors were considered. A consistent configuration of factors emerged where participants preferred to use a teleportation technique for navigation (compared to walking-in-place), a full-body representation (rather than hands only), the responsiveness of virtual human characters (compared to being ignored) and realistic compared to cartoon rendering. We propose this new method to evaluate participant choices and discuss various extensions.


The current use of human cadaveric models in urology: a systematic review.
We aim to perform a systematic review of the current use of cadaveric models in urology and analyze their role within urological training and the experimentation of novel surgical techniques. A systematic review of the current literature was conducted through the Medline and NCBI PubMed, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL) databases in September 2019. All papers published after 2000, concerning studies conducted on human cadaveric models for training in urological surgical procedures, developing of new techniques and technologies were considered for the review. From the literature search we found a total of 3769 different articles of those only 58 articles were included in the study. Eleven studies (19%) were published between 2000 and 2009, and the trend increased almost fourfold in the following period (2010-2019) with 47 studies (81%) being published. Surprisingly, a clear statement on the approval of the use of cadavers was written in less than 50% of the studies. About the 48% of the studies were aimed to experiment a novel surgical technique while in the 31% of studies the cadavers were used for surgical training. More than half of the studies evaluated did not provide any information about the type and method of preparation of cadaveric models while specific outcomes in terms of satisfaction with the use of cadaver models were reported clearly only in less than a third of them. The quality of the materials and methods described in most studies is often characterized by poor detail with regards to the preservation and preparation of the bodies and the satisfaction of use, which might affect training and testing.


Effect of co-trimoxazole and N-acetylcysteine alone and in combination on bacterial adherence on ureteral stent surface.
To assess the effect of co-trimoxazole and N-acetylcysteine (NAC), alone and in combination, on bacterial adherence to biofilm formed on ureteral stent surfaces. This prospective randomized study was conducted on 636 patients who underwent double J ureteral stent insertion after variable urological procedures. Patients were randomized into four groups: A (n = 165), no antibiotics or mucolytics during stent indwelling; B (n = 153), oral NAC (200 mg/day for children aged < 12 years old and 600 mg/day for adults) during stent indwelling; C (n = 162), oral co-trimoxazole (2 mg TMP/kg/day) during stent indwelling; and D (n = 156), both oral NAC and co-trimoxazole during stent indwelling. Two weeks following double J stent (JJ stent) insertion, urinalysis was performed on all patients and urine culture was done for all the patients at the day of double J stent removal. The stent was removed 2 weeks postoperatively, and a stent segment sized 3-5 cm from the bladder segment of the stent was sent for culture. Positive stent cultures were found in 63.6% (105/165), 43.1% (66/153), 37% (60/162), and 19.2% (30/156) patients of groups A, B, C, and D, respectively. E. coli was the organism most commonly isolated from the stent culture in all groups. The combination of co-trimoxazole and NAC was more effective in reducing bacterial adherence on ureteral stent surfaces than either alone.


A SURVEY ON MOSQUITO CONTROL KNOWLEDGE AND INSECTICIDE USE IN NEW ORLEANS, LA, 2020-2021.
Mosquitoes are a known public nuisance and can vector various diseases. Historically, New Orleans, LA, has long been acquainted with the burden of mosquito-borne diseases, such as malaria and yellow fever in the 20th century and West Nile virus in the 21st century. Government mosquito control awareness campaigns have been around for decades as has the use of organophosphate and pyrethroid insecticides by mosquito abatement districts. However, few data are available on public perception of mosquito control and public usage of insecticides to kill mosquitoes in New Orleans. We conducted a survey from August 2020 to July 2021 to evaluate New Orleans residents' 1) general knowledge regarding mosquito control and 2) what measures and products they use to control mosquitoes. The aim of this survey was to determine how residents contribute to backyard mosquito control by do-it-yourself or professional applications of insecticides. The survey was disseminated both online and via mail. Of the 396 survey participants, nearly all (99.48%) agreed that mosquito control is important in New Orleans because it prevents mosquito bites (30.85%), prevents mosquito borne-diseases (38.51%), and prevents nuisance mosquitoes (29.17%). More than one-third (35%) of survey participants indicated that they empty containers to reduce adult mosquitoes on their own property. More than two-thirds of the participants (69.95%) would not hire a pest management professional to spray their yard for adult mosquitoes, and only 20% of survey participants do apply a pesticide to kill adult mosquitoes on their own property. None of our findings were associated with the level of education, gender, or age of participants. This study suggests that the City of New Orleans Mosquito, Termite and Rodent Control Board educational and outreach campaigns may be an effective tool in spreading mosquito control awareness and contribute to residents' knowledge of mosquito control. The data we collected indicate that residents understand what mosquito control is and why it is important in New Orleans.


Complement receptor 1 gene polymorphisms in sarcoidosis.
Sarcoidosis is likely to result from exposure of genetically susceptible hosts to environmental agents. Erythrocyte (E) complement receptor 1 (CR1) is a membrane protein mediating the transport of immune complexes (ICs) to phagocytes, and at least three polymorphisms on the CR1 gene are related to erythrocyte surface density of CR1 molecules, in turn related to the rate of IC clearance from circulation. We hypothesized that sarcoidosis could be associated with increased frequency of the CR1 gene alleles coding for reduced CR1/E ratio. We studied 91 sarcoid patients and two control groups: 94 healthy volunteers and 71 patients with chronic obstructive pulmonary disease (COPD). Three polymorphic sites of CR1 gene, His1208Arg, intron 27 HindIII/RFLP, and Pro1827Arg, were analyzed. The three polymorphisms were in linkage disequilibrium. The GG genotype for the Pro1827Arg (C(5507)G) polymorphism was significantly associated with sarcoidosis in comparison to both control groups (odds ratio [OR] = 3.13; 95% confidence interval [CI] 1.49-6.69 versus healthy control subjects, and OR= 2.82, 95% CI 1.27-6.39 versus COPD control subjects). The same genotype was particularly associated to disease in females (OR = 7.05; 95% CI 3.10-16.61 versus healthy control subjects). These findings agree with speculations on the role of CR1 gene as a possible susceptibility factor.


[Neuroplasticity as a basis for early rehabilitation of stroke patients].
The review is devoted to the current state of the problem of early rehabilitation of stroke patients. The rate of primary disability in patients after stroke is 3.2 per 10000 population but only 20% of previously working patients return to work. Early rehabilitation is treatment actions during a period following stroke. Adequate treatment during this period may decrease the extent of brain damage and improve disease outcome. The complexity of rehabilitation consists in using several complementary pharmacological and non-pharmacological rehabilitation measures. Appearance of new techniques of rehabilitation treatment aimed at neuroplasticity stimulation increases treatment potential of rehabilitative technologies.


Quantifying the force in flow-cell based single-molecule stretching experiments.
The flow-cell based single-molecule manipulation technique has found many applications in the study of DNA mechanics and protein-DNA interactions. However, the force in these experiments has not been fully characterized and is usually limited to a moderate force regime (<25 pN). In this work, using the "tethered-bead" assay, the hydrodynamic drag of DNA has been quantitatively evaluated based on a "bead-spring chain" model. The force derived from the Brownian motion of the bead thus contains both contributions from this equivalent hydrodynamic drag of DNA and the pulling force from the tethered bead. Next, using flow-cell based DNA pulling experiments, the linear relationship between the flow rate and total hydrodynamic force on the bead-DNA system has been demonstrated to be valid over a wide force range (0-110 pN). Consequently, the force can be directly converted from the flow rate by a linear factor that can be calibrated either by the bead's Brownian motion at low flow rates or using DNA overstretching transition. Furthermore, the hydrodynamic force and torque due to the shear flow on the bead as well as the equivalent stretching force on DNA are calculated based on theoretical models with the hydrodynamic drag on DNA also considered. The calculated force-extension curves show a good agreement with the measured ones. These results offer important insights into the force in flow-cell based single-molecule stretching experiments and provide a foundation for establishing flow-cells as a simple, low-cost, yet flexible and precise tool for single-molecule force measurements over a wide force range.


Panretinal photocoagulation in central retinal vein occlusion: A randomised controlled clinical study.
A randomised controlled study of photocoagulation compared with no treatment in central retinal vein occlusion is reported. Forty-eight patients were allocated into treated and control groups by a random procedure 3 months after their first visual symptoms. For the analysis they were subdivided into (1) ischaemic type, and (2) hyperpermeability-response macular-oedema type of central retinal vein occlusion. In neither group did treatment confer benefit as far as visual acuity was concerned. However, iris, disc, and retinal neovascularisation improved after treatment in the ischaemic group. In addition none of the treated patients progressed to neovascular glaucoma. Macular-oedema improved in treated patients with the hyperpermeability response, but the visual field was affected and atrophic changes at the macular precluded visual improvement. It is concluded that photocoagulation should be used only to prevent complications in the ischaemic type of central retinal vein occlusion. It does not appear to be of value in the hyperpermeability group.


Prognostic factors for radiosurgery treatment of trigeminal neuralgia.
Trigeminal neuralgia treatment results are thought to be highly dependent upon selection criteria. We retrospectively analyzed a series of patients to determine the likelihood of treatment success for patients treated with radiosurgery. A retrospective analysis of 82 patients treated with linear accelerator radiosurgery was undertaken with a median follow-up period of 18 months. Patients were evaluated with a standard inventory using the Barrow Neurological Institute pain scale as the primary means of outcome measurement. Patients were treated with a linear accelerator using a single isocenter plan delivered via a 4-mm collimator, typically with seven noncoplanar arcs to a peak dose of 85 or 90 Gy in primary treatments and 60 Gy in retreatments. The primary target was the cisternal component of the trigeminal nerve. Posttreatment outcomes were analyzed in light of pretreatment patient characteristics, including age, sex, anticonvulsant responsiveness, quality and pattern of pain, length of disease, number of previous procedures, and radiation dose exposure to the root entry zone. Univariate analysis and multivariate logistic regression analysis were used to determine the prognostic significance of various pretreatment variables. Good results as defined by a Barrow Neurological Institute outcome score of IIIb or better were seen in 85.3% of patients. Excellent results as defined by a Barrow Neurological Institute outcome score of I were seen in 49% of patients. The median time to satisfactory improvement of pain was 4 weeks. Only one variable, sensitivity to anticonvulsant medication, was found to be statistically significant in both univariate (P = 0.003) and multivariate analysis (P = 0.025). All other variables analyzed failed to reach statistical significance. Complications were not common, with seven patients (8.5%) developing new-onset hypoesthesia and two patients (2%) developing dry eye symptoms. Anticonvulsant responsiveness is the single most important prognostic indicator of treatment success for patients presenting with facial pain. Other predictive factors generally failed to reach statistical significance. Linear accelerator radiosurgery for trigeminal neuralgia is a safe and effective treatment for well-selected patients, with results similar to those obtained with gamma unit radiosurgery.


Acute myeloid leukemia with t(10;17)(p13;q12) chromosome translocation: a case report and literature review.
More than 50% of adult patients with acute myeloid leukemia (AML) carry chromosome abnormalities, like t(8;21)(q22;q22), t(15;17), t(8;21)inv(16) or t(16;16). t(10;17) translocation was very rare in AML. There are only 10 such cases reported in the literature. Here, we describe a case of acute myeloid leukemia with t(10;17)(p13;q12) chromosome translocation, who had complete remission after one course of chemotherapy.


Transient middle cerebral artery occlusion induces microglial priming in the lumbar spinal cord: a novel model of neuroinflammation.
Middle cerebral artery occlusion (MCAo) in mice results in a brain infarct, the volume of which depends on the length of occlusion. Following permanent occlusion, neuropathological changes - including a robust glial inflammatory response - also occur downstream of the infarct in the spinal cord. We have performed short, transient MCAo in mice to induce penumbral damage spanning the motor cortex. A 30 minute MCAo using a poly-L-lysine-coated intraluminal suture introduced through a common carotid artery incision was performed in 17 female C57BL/6 mice. Five sham-operated mice received common carotid artery ligation without insertion of the suture. Neurobehavioural assessments were performed during occlusion, immediately following reperfusion, and at 24 and 72 hours post-reperfusion. Routine histological and immunohistochemical studies were performed at 24 and 72 hours. In 11 of the surviving 16 mice subjected to MCAo, we observed a focal, subcortical necrotic lesion and a reproducible, diffuse cortical lesion with accompanying upper motor neuron involvement. This was associated with contralateral ventral spinal cord microglial priming without significant reactive astrocytosis or lower motor neuron degeneration. The advantages to this method are that it yields a reproducible cortical lesion, the extent of which is predictable using behavioural testing during the period of ischemia, with upper motor neuron involvement and downstream priming, but not full activation, of microglia in the lumbar spinal cord. In addition, survival is excellent following the 30 minutes of occlusion, rendering this a novel and useful model for examining the effects of microglial priming in the spinal motor neuron pool.


Human extravillous trophoblast invasion: intrinsic and extrinsic regulation.
During the establishment of pregnancy, a human blastocyst implants into the uterine endometrium to facilitate the formation of a functional placenta. Implantation involves the blastocyst adhering to the uterine luminal epithelium before the primitive syncytiotrophoblast and subsequently specialised cells, the extravillous trophoblast (EVT), invade into the decidua in order to engraft and remodel uterine spiral arteries, creating the placental blood supply at the end of the first trimester. Defects in EVT invasion lead to abnormal placentation and thus adverse pregnancy outcomes. The local decidual environment is thought to play a key role in regulating trophoblast invasion. Here we describe the major cell types present in the decidua during the first trimester of pregnancy and review what is known about their regulation of EVT invasion. Overall, the evidence suggests that in a healthy pregnancy almost all cell types in the decidua actively promote EVT invasion and, further, that reduced EVT invasion towards the end of the first trimester is regulated, in part, by the reduced invasive capacity of EVTs shown at this time.


Limited evidence for the use of imaging to detect prostate cancer: a systematic review.
To assess the diagnostic accuracy of imaging technologies for detecting prostate cancer in patients with elevated PSA-values or suspected findings on clinical examination. The databases Medline, EMBASE, Cochrane, CRD HTA/DARE/NHS EED and EconLit were searched until June 2013. Pre-determined inclusion criteria were used to select full text articles. Risk of bias in individual studies was rated according to QUADAS or AMSTAR. Abstracts and full text articles were assessed independently by two reviewers. The performance of diagnostic imaging was compared with systematic biopsies (reference standard) and sensitivity and specificity were calculated. The literature search yielded 5141 abstracts, which were reviewed by two independent reviewers. Of these 4852 were excluded since they did not meet the inclusion criteria. 288 articles were reviewed in full text for quality assessment. Six studies, three using MRI and three using transrectal ultrasound were included. All were rated as high risk of bias. Relevant studies on PET/CT were not identified. Despite clinical use, there is insufficient evidence regarding the accuracy of imaging technologies for detecting cancer in patients with suspected prostate cancer using TRUS guided systematic biopsies as reference standard.


Re-ordered fuzzy conformance checking for uncertain clinical records.
Modern hospitals implement clinical pathways to standardize patients' treatments. Conformance checking techniques provide an automated tool to assess whether the actual executions of clinical processes comply with the corresponding clinical pathways. However, clinical processes are typically characterized by a high degree of uncertainty, both in their execution and recording. This paper focuses on uncertainty related to logging clinical processes. The logging of the activities executed during a clinical process in the hospital information system is often performed manually by the involved actors (e.g., the nurses). However, such logging can occur at a different time than the actual execution time, which hampers the reliability of the diagnostics provided by conformance checking techniques. To address this issue, we propose a novel conformance checking algorithm that leverages principles of fuzzy set theory to incorporate experts' knowledge when generating conformance diagnostics. We exploit this knowledge to define a fuzzy tolerance in a time window, which is then used to assess the magnitude of timestamp violations of the recorded activities when evaluating the overall process execution compliance. Experiments conducted on a real-life case study in a Dutch hospital show that the proposed method obtains more accurate diagnostics than the state-of-the-art approaches. We also consider how our diagnostics can be used to stimulate discussion with domain experts on possible strategies to mitigate logging uncertainty in the clinical practice.


Stem Cells, Helicobacter pylori, and Mutational Landscape: Utility of Preclinical Models to Understand Carcinogenesis and to Direct Management of Gastric Cancer.
Several genetic and environmental factors increase gastric cancer (GC) risk, with Helicobacter pylori being the main environmental agent. GC is thought to emerge through a sequence of morphological changes that have been elucidated on the molecular level. New technologies have shed light onto pathways that are altered in GC, involving mutational and epigenetic changes and altered signaling pathways. Using various new model systems and innovative approaches, the relevance of such alterations for the emergence and progression of GC has been validated. Here, we highlight the key strategies and the resulting achievements. A major step is the characterization of epithelial stem cell behavior in the healthy stomach. These data, obtained through new reporter mouse lines and lineage tracing, enabled insights into the processes that control cellular proliferation, self-renewal, and differentiation of gastric stem cells. It has become evident that these cells and pathways are often deregulated in carcinogenesis. Second, insights into how H pylori colonizes gastric glands, directly interacts with stem cells, and alters cellular and genomic integrity, as well as the characterization of tissue responses to infection, provide a comprehensive picture of how this bacterium contributes to gastric carcinogenesis. Third, the development of stem cell- and tissue-specific reporter mice have driven our understanding of the signals and mutations that promote different types of GC and now also enable the study of more advanced, metastasized stages. Finally, organoids from human tissue have allowed insights into gastric carcinogenesis by validating mutational and signaling alterations in human primary cells and opening a route to predicting responses to personalized treatment.


Dissecting Fertility Functions of Drosophila Y Chromosome Genes with CRISPR.
Gene-poor, repeat-rich regions of the genome are poorly understood and have been understudied due to technical challenges and the misconception that they are degenerating "junk." Yet multiple lines of evidence indicate these regions may be an important source of variation that could drive adaptation and species divergence, particularly through regulation of fertility. The ∼40 Mb Y chromosome of Drosophila melanogaster contains only 16 known protein-coding genes, and is highly repetitive and entirely heterochromatic. Most of the genes originated from duplication of autosomal genes and have reduced nonsynonymous substitution rates, suggesting functional constraint. We devised a genetic strategy for recovering and retaining stocks with sterile Y-linked mutations and combined it with CRISPR to create mutants with deletions that disrupt three Y-linked genes. Two genes, PRY and FDY, had no previously identified functions. We found that PRY mutant males are subfertile, but FDY mutant males had no detectable fertility defects. FDY, the newest known gene on the Y chromosome, may have fertility effects that are conditional or too subtle to detect. The third gene, CCY, had been predicted but never formally shown to be required for male fertility. CRISPR targeting and RNA interference of CCY caused male sterility. Surprisingly, however, our CCY mutants were sterile even in the presence of an extra wild-type Y chromosome, suggesting that perturbation of the Y chromosome can lead to dominant sterility. Our approach provides an important step toward understanding the complex functions of the Y chromosome and parsing which functions are accomplished by genes vs. repeat elements.


[Percutaneous laser denervation of the zygapophyseal joints in the pain facet syndrome].
Percutaneous laser denervation of archoappendicular joints in spinal pain was made in 15 patients from a study group. Percutaneous high-frequency denervation of archoappendicular joints was performed in a control group consisting of 15 patients with facet syndrome. A preoperative protocol for each patient included at least two diagnostic segmental blocks. A surgical intervention was morphologically substantiated during an experiment; the most optimum surgery protocol was chosen. Destruction was performed by 0.97-micron laser radiation for 4-6 sec at 5-10 W. The number of cases of a complete or partial pain regression, the duration of its impact, side effects and complications were determined. Of the 15 patients from the study group, 8 and 6 patients were observed to have a complete and significant pain regression (more than 50% of the baseline). No effect was achieved in one patient. The similar results were obtained in the control group. There were no postoperative infectious complications in the patients of both groups; transient pain dysesthesia was registered in one case. The findings have led to the conclusion that laser denervation of archoappendicular joints is effective in the pain facet syndrome.


Antigen-specific and nonspecific deletion of immature cortical thymocytes caused by antigen injection.
Analysis of antigen-induced negative selection of thymocytes in T cell receptor (TCR)-transgenic mice is complicated by the presence of an antigen-responsive peripheral T cell compartment. Our experiments address the question of whether and how peripheral T cell activation can affect immature thymocytes. Following three daily injections of peptide antigen into mice expressing a peptide-specific transgenic TCR and deficient for TAP1, we and others have found profound deletion of the CD4+CD8+ (DP) thymocyte subset. However, our work shows that even though mature CD8+ T cells are inefficiently selected in TAP1-deficient mice, there was a striking degree of peripheral expansion and activation of CD8+ peripheral T cells. Furthermore, when cells from TCR-transgenic mice were adoptively transferred, we found that deletion of nontransgenic DP thymocytes occurred in Thy-1-congenic and even more efficiently in TAP1-deficient recipients after repeated peptide injection resulting in peripheral T cell activation. In the adoptive transfer experiments the degree of deletion of immature bystander thymocytes was decreased upon blocking of TNF. These data show that deletion of DP thymocytes can result from excessive peripheral T cell activation and identify TNF as an important effector molecule for this process. When steps are taken to avoid peripheral T cell activation, peptide antigen can induce TCR-mediated thymocyte deletion, presumably in the thymus cortex, since injection of TAP1-deficient TCR-transgenic mice resulted in deletion of immature DP thymocytes prior to detectable peripheral T cell expansion and activation. This effect was not blocked by inhibiting tumor necrosis factor activity. In addition, DP depletion was seen in the absence of peripheral T cell activation when antibody-mediated depletion of CD8+ T cells was performed. Our work clearly shows that two mechanisms for deletion of DP thymocytes exist: deletion induced by antigen presentation in the thymus and deletion as a consequence of repeated stimulation of mature peripheral T cells.


First experience with the new extracorporeal membrane oxygenation system Colibrì.
Extracorporeal membrane oxygenation (ECMO) is increasingly used for circulatory or pulmonary support not only in-hospital but also out-of-hospital. Small dimensions and a lightweight design are important, especially for out-of-hospital use but also for intra-hospital transportation of patients who require ECMO support. We share our first experience with the new Colibrì ECMO system. From December 2022 to January 2023, we used the new Colibrì extracorporeal circulation (ECC) system in six patients with cardiac or pulmonary failure. The Colibrì system was used in-hospital in six patients with post-cardiac surgery low output syndrome, respiratory failure due to influenza or acute respiratory distress syndrome, cardiogenic shock, pulmonary embolism, and failed weaning from cardiopulmonary bypass. The system was implanted in venovenous (VV) and venoarterial (VA) fashion in 3 patients, respectively. In one patient, the configuration was switched from VA to VV after cardiac recovery. One patient received left-ventricular unloading using the IMPELLA®5.5. ECMO run time was 1 to 13 days. We did not notice any ECC system-associated complications. No ECMO system changes were required. Our case series concludes that the new Colibrì system is safe and effective for in-hospital ECMO indications. The small dimensions and lightweight design are very beneficial for the transportation of patients. It might be especially helpful for out-of-hospital situations.


The Role of Galectin-3 in the Kidneys.
Galectin-3 is a 32- to 35-kDa member of the galectin family of b-galactoside-binding lectins, which is characterized by a carbohydrate recognition domain. Through its carbohydrate-binding function, it regulates cell growth, differentiation, and inflammation. It also plays a complex, context-dependent role in the kidneys. During development, it promotes nephrogenesis and is strongly expressed in the ureteric bud and its derivatives. An increase in the concentration of galectin-3 has been reported to be associated with fibrosis of the kidneys. Elevated levels of plasma galectin-3 are also associated with increased risks of rapid renal function decline, incident chronic kidney disease, and progressive renal impairment, and also with cardiovascular end points, infection, and all-cause mortality in patients with renal function impairment. This review discusses a general survey on galectin-3 expressions in nephrogenesis, kidney injury animal models, clinical renal diseases, renal transplantation and the potential role of galectin-3 for treatment in kidney disease.


Label Propagation via Teaching-to-Learn and Learning-to-Teach.
How to propagate label information from labeled examples to unlabeled examples over a graph has been intensively studied for a long time. Existing graph-based propagation algorithms usually treat unlabeled examples equally, and transmit seed labels to the unlabeled examples that are connected to the labeled examples in a neighborhood graph. However, such a popular propagation scheme is very likely to yield inaccurate propagation, because it falls short of tackling ambiguous but critical data points (e.g., outliers). To this end, this paper treats the unlabeled examples in different levels of difficulties by assessing their reliability and discriminability, and explicitly optimizes the propagation quality by manipulating the propagation sequence to move from simple to difficult examples. In particular, we propose a novel iterative label propagation algorithm in which each propagation alternates between two paradigms, teaching-to-learn and learning-to-teach (TLLT). In the teaching-to-learn step, the learner conducts the propagation on the simplest unlabeled examples designated by the teacher. In the learning-to-teach step, the teacher incorporates the learner's feedback to adjust the choice of the subsequent simplest examples. The proposed TLLT strategy critically improves the accuracy of label propagation, making our algorithm substantially robust to the values of tuning parameters, such as the Gaussian kernel width used in graph construction. The merits of our algorithm are theoretically justified and empirically demonstrated through experiments performed on both synthetic and real-world data sets.


Integrative Review of Programs to Improve Outcomes for Children With Comorbid Asthma and Anxiety/Depressive Symptoms.
Asthma is one of the most common pediatric chronic physical conditions. Youth with comorbid asthma and anxiety/depressive symptoms tend to have less controlled asthma and an increased use of health services in schools. The purpose of this integrative review was to examine the literature on educational and behavioral/ cognitive behavioral skills interventions for children with asthma and anxiety/depressive symptoms. Five electronic databases and forward/backward citations were searched. Eleven peer reviewed articles were retained for review. Main findings of the limited evidence suggest that educational and behavioral/cognitive behavioral skills programs may increase asthma knowledge and asthma-related self-efficacy while reducing anxiety/depressive symptoms. One study showed a decrease in use of quick relief inhalers and another had increased adherence to asthma controller medication. The literature indicates that educational and cognitive behavioral skills programs can have a positive impact on children with asthma and symptoms of anxiety/depression. School-based skills programs had better retention than outpatient programs.


Synthetic and structural study of the coordination chemistry of a peri-backbone-supported phosphino-phosphonium salt.
Coordination chemistry of an acenaphthene peri-backbone-supported phosphino-phosphonium chloride (1) was investigated, revealing three distinct modes of reactivity. The reaction of 1 with Mo(CO)4(nor) gives the Mo(0) complex [(1)Mo(CO)4Cl] (2), in which the ligand 1 exhibits monodentate coordination through the phosphine donor and the P-P bond is retained. PtCl2(cod) reacts with the chloride and triflate salts of 1 to form a mononuclear complex [(1Cl)PtCl2] (3) and a binuclear complex [((1Cl)PtCl)2][2TfO] (4), respectively. In both of these complexes, the platinum center adds across the P-P bond, and subsequent chloride transfer to the phosphenium center results in phosphine-chlorophosphine bidentate coordination. [((1)PdCl)2] (5) was isolated from the reaction of 1 and Pd2(dba)3 (dba = dibenzylideneacetone). Oxidative addition to palladium(0) results in a heteroleptic phosphine bridging phosphide coordination to the Pd(II) center. In addition, reaction of 1 with BH3·SMe2 leads to the bis(borane) adduct of the corresponding mixed tertiary/secondary phosphine (6), with BH3 acting as both a reducing agent and a Lewis acid. The new compounds were fully characterized, including X-ray diffraction. The ligand properties of 1 and related bonding issues are discussed with help of DFT computations.


Postinsertional processing of sucrase-alpha-dextrinase precursor to authentic subunits: multiple step cleavage by trypsin.
Sucrase-alpha-dextrinase, a hybrid digestive carbohydrase of the intestinal brush border, is initially synthesized and transported to the surface membrane as a single-chain glycoprotein, P, which is then cleaved to alpha- and beta-subunits, presumably by one or more pancreatic proteases. However, efforts to convert P under controlled conditions to authentic alpha and beta have been unsuccessful. Sucrase-dextrinase immunoprecipitates from rats intraintestinally labeled with [3H]leucine or [35S]methionine without presence of biliary-pancreatic secretions revealed only the 230-kDa P precursor. Restoration of intestinal flow converted the brush border P to the alpha- (140 kDa) and beta- (125 kDa) subunits. Biliary plus pancreatic secretions facilitated this postinsertional cleavage, but bile alone played no role in conversion. When isolated brush borders, prelabeled in vivo, were exposed to a mixture of pancreatic proteases at physiological concentrations, P was converted to authentic alpha and beta, but only trypsin was responsible for the conversion. Kinetic analysis in prelabeled isolated brush-border vesicles revealed the appearance of several intermediate species (205-145 kDa) produced either by endogenous membrane proteases or by trypsin itself. Reconstituted duodenal luminal contents yielded a fragmentation pattern identical to that produced by trypsin alone. Trypsin was necessary and sufficient for processing of the intermediate precursors to the final authentic alpha- and beta-subunits. Based on the alpha- to beta radioactivity ratio and the known amino acid composition of the subunits, differential cleavage occurred with relatively greater production of the beta-subunit (alpha-to-beta molar ratio = 0.77). The conversion of P to the alpha- and beta-units, rather than occurring in a single step after membrane insertion, is differentially catalyzed by trypsin trimming to unequal amounts of the subunits involving a complex series of cleavage steps.


Microbial deterioration of stone monuments--an updated overview.
Cultural heritage monuments may be discolored and degraded by growth and activity of living organisms. Microorganisms form biofilms on surfaces of stone, with resulting aesthetic and structural damage. The organisms involved are bacteria (including actinomycetes and cyanobacteria), fungi, archaea, algae, and lichens. Interactions between these organisms and stone can enhance or retard the overall rate of degradation. Microorganisms within the stone structure (endoliths) also cause damage. They grow in cracks and pores and may bore into rocks. True endoliths, present within the rock, have been detected in calcareous and some siliceous stone monuments and are predominantly bacterial. The taxonomic groups differ from those found epilithically at the same sites. The nature of the stone substrate and the environmental conditions influence the extent of biofilm colonization and the biodeterioration processes. A critical review of work on microbial biofilms on buildings of historic interest, including recent innovations resulting from molecular biology, is presented and microbial activities causing degradation are discussed.


Adrenal tumors treated by adrenalectomy following spontaneous rupture carry an overall favorable prognosis: retrospective evaluation of outcomes in 59 dogs and 3 cats (2000-2021).
To conduct a retrospective multi-institutional study reporting short- and long-term outcomes of adrenalectomy in patients presenting with acute hemorrhage secondary to spontaneous adrenal rupture. 59 dogs and 3 cats. Medical records of dogs and cats undergoing adrenalectomy between 2000 and 2021 for ruptured adrenal masses were reviewed. Data collected included clinical presentation, preoperative diagnostics, surgical report, anesthesia and hospitalization findings, histopathology, adjuvant treatments, and long-term outcome (recurrence, metastasis, and survival). Median time from hospital admission to surgery was 3 days, with 34% of surgeries being performed emergently (within 1 day of presentation). Need for intraoperative blood transfusion was significantly associated with emergent surgery and presence of active intraoperative hemorrhage. The short-term (≤ 14 days) complication and mortality rates were 42% and 21%, respectively. Negative prognostic factors for short-term survival included emergent surgery, intraoperative hypotension, and performing additional surgical procedures. Diagnoses included adrenocortical neoplasia (malignant [41%], benign [12%], and undetermined [5%]), pheochromocytoma (38%), a single case of adrenal fibrosis and hemorrhage (2%), and a single case of hemangiosarcoma (2%). Local recurrence and metastasis of adrenocortical carcinoma were confirmed in 1 and 3 cases, respectively. Overall median survival time was 574 days and 900 days when short-term mortality was censored. No significant relationship was found between histopathological diagnosis and survival. Adrenalectomy for ruptured adrenal gland masses was associated with similar short- and long-term outcomes as compared with previously reported nonruptured cases. If hemodynamic stability can be achieved, delaying surgery and limiting additional procedures appear indicated to optimize short-term survival.


The effect of music reinforcement for non-nutritive sucking on nipple feeding of premature infants.
In this randomized, controlled multi-site study, the pacifier-activated-lullaby system (PAL) was used with 68 premature infants. Dependent variables were (a) total number of days prior to nipple feeding, (b) days of nipple feeding, (c) discharge weight, and (d) overall weight gain. Independent variables included contingent music reinforcement for non-nutritive sucking for PAL intervention at 32 vs. 34 vs. 36 weeks adjusted gestational age (AGA), with each age group subdivided into three trial conditions: control consisting of no PAL used vs. one 15-minute PAL trial vs. three 15-minute PAL trials. At 34 weeks, PAL trials significantly shortened gavage feeding length, and three trials were significantly better than one trial. At 32 weeks, PAL trials lengthened gavage feeding. Female infants learned to nipple feed significantly faster than male infants. It was noted that PAL babies went home sooner after beginning to nipple feed, a trend that was not statistically significant.


Short-term effect of the soil amendments activated carbon, biochar, and ferric oxyhydroxide on bacteria and invertebrates.
The aim of the present study was to evaluate the secondary ecotoxicological effects of soil amendment materials that can be added to contaminated soils in order to sequester harmful pollutants. To this end, a nonpolluted agricultural soil was amended with 0.5, 2, and 5% of the following four amendments: powder activated carbon (PAC), granular activated carbon, corn stover biochar, and ferric oxyhydroxide powder, which have previously been proven to sequester pollutants in soil. The resulting immediate effects (i.e., without aging the mixtures before carrying out tests) on the springtail Folsomia candida, the earthworm species Aporectodea caliginosa and Eisenia fetida, the marine bacteria Vibrio fischeri, a suite of ten prokaryotic species, and a eukaryote (the yeast species Pichia anomalia) were investigated. Reproduction of F. candida was significantly increased compared to the unamended soil when 2% biochar was added to it. None of the treatments caused a negative effect on reproduction. All amendments had a deleterious effect on the growth of A. caliginosa when compared to the unamended soil, except the 0.5% amendment of biochar. In avoidance tests, E. fetida preferred biochar compared to all other amendments including the unamended soil. All amendments reduced the inhibition of luminescence to V. fischeri, i.e., were beneficial for the bacteria, with PAC showing the greatest improvement. The effects of the amendments on the suite of prokaryotic species and the eukaryote were variable, but overall the 2% biochar dose provided the most frequent positive effect on growth. It is concluded that the four soil amendments had variable but never strongly deleterious effects on the bacteria and invertebrates studied here during the respective recommended experimental test periods.


HPLC-DAD Analysis, SFE-CO2 Extraction, and Antibacterial Activity on Bioactive Compounds from Mosla chinensis Maxim.
Mosla chinensis Maxim is an annual herb with many potential purposes in agricultural, industrial, and pharmaceutical fields. At present, the extract of the whole plant from M. chinensis has been proven to demonstrate antifungal, antioxidant, and anti-inflammatory activities. Previous studies focused on the enzyme pretreatment in hydrodistillation from M. chinensis. However, organic solvent or supercritical fluid carbon dioxide extraction (SFE-CO2) methods, which are commonly utilized in industry, have seldom been studied and cannot provide multiple evaluations of yield. In this work, we analysed compounds from M. chinensis by HPLC-DAD, discussed n-hexane extraction, and conducted further investigations on SFE-CO2 through the design of response surface methodology (RSM). The sample obtained from pilot-scale SFE-CO2 was also tested against nine kinds of microorganisms. Single-factor results revealed that the extraction rates from M. chinensis by steam distillation, n-hexane extraction, and SFE-CO2 were 1%, 2.09%, and 3.26%, respectively. RSM results showed a significant improvement in extraction rate through optimising pressure and time, and the interaction of both factors was more important than that of temperature-pressure and temperature-time. A pilot-scale test with an extraction rate of 3.34% indicated that the predicted RSM condition was operable. In addition, samples from the pilot-scale SFE-CO2 showed antibacterial effects against three previously unreported bacteria (Gardnerella vaginalis, methicillin-resistant Staphylococcus aureus, and Propionibacterium acnes). These results fill the gap in previous research and provide more information for the application and development of M. chinensis in the future.


GRP78 and Integrins Play Different Roles in Host Cell Invasion during Mucormycosis.
Mucormycosis, caused by Rhizopus species, is a life-threatening fungal infection that occurs in patients immunocompromised by diabetic ketoacidosis (DKA), cytotoxic chemotherapy, immunosuppressive therapy, hematologic malignancies, or severe trauma. Inhaled Rhizopus spores cause pulmonary infections in patients with hematologic malignancies, while patients with DKA are much more prone to rhinoorbital/cerebral mucormycosis. Here, we show that Rhizopus delemar interacts with glucose-regulated protein 78 (GRP78) on nasal epithelial cells via its spore coat protein CotH3 to invade and damage the nasal epithelial cells. Expression of the two proteins is significantly enhanced by high glucose, iron, and ketone body levels (hallmark features of DKA), potentially leading to frequently lethal rhinoorbital/cerebral mucormycosis. In contrast, R. delemar CotH7 recognizes integrin β1 as a receptor on alveolar epithelial cells, causing the activation of epidermal growth factor receptor (EGFR) and leading to host cell invasion. Anti-integrin β1 antibodies inhibit R. delemar invasion of alveolar epithelial cells and protect mice from pulmonary mucormycosis. Our results show that R. delemar interacts with different mammalian receptors depending on the host cell type. Susceptibility of patients with DKA primarily to rhinoorbital/cerebral disease can be explained by host factors typically present in DKA and known to upregulate CotH3 and nasal GRP78, thereby trapping the fungal cells within the rhinoorbital milieu, leading to subsequent invasion and damage. Our studies highlight that mucormycosis pathogenesis can potentially be overcome by the development of novel customized therapies targeting niche-specific host receptors or their respective fungal ligands.IMPORTANCE Mucormycosis caused by Rhizopus species is a fungal infection with often fatal prognosis. Inhalation of spores is the major route of entry, with nasal and alveolar epithelial cells among the first cells that encounter the fungi. In patients with hematologic malignancies or those undergoing cytotoxic chemotherapy, Rhizopus causes pulmonary infections. On the other hand, DKA patients predominantly suffer from rhinoorbital/cerebral mucormycosis. The reason for such disparity in disease types by the same fungus is not known. Here, we show that the unique susceptibility of DKA subjects to rhinoorbital/cerebral mucormycosis is likely due to specific interaction between nasal epithelial cell GRP78 and fungal CotH3, the expression of which increases in the presence of host factors present in DKA. In contrast, pulmonary mucormycosis is initiated via interaction of inhaled spores expressing CotH7 with integrin β1 receptor, which activates EGFR to induce fungal invasion of host cells. These results introduce a plausible explanation for disparate disease manifestations in DKA versus those in hematologic malignancy patients and provide a foundation for development of therapeutic interventions against these lethal forms of mucormycosis.


Explicit attention interferes with selective emotion processing in human extrastriate cortex.
Brain imaging and event-related potential studies provide strong evidence that emotional stimuli guide selective attention in visual processing. A reflection of the emotional attention capture is the increased Early Posterior Negativity (EPN) for pleasant and unpleasant compared to neutral images (approximately 150-300 ms poststimulus). The present study explored whether this early emotion discrimination reflects an automatic phenomenon or is subject to interference by competing processing demands. Thus, emotional processing was assessed while participants performed a concurrent feature-based attention task varying in processing demands. Participants successfully performed the primary visual attention task as revealed by behavioral performance and selected event-related potential components (Selection Negativity and P3b). Replicating previous results, emotional modulation of the EPN was observed in a task condition with low processing demands. In contrast, pleasant and unpleasant pictures failed to elicit increased EPN amplitudes compared to neutral images in more difficult explicit attention task conditions. Further analyses determined that even the processing of pleasant and unpleasant pictures high in emotional arousal is subject to interference in experimental conditions with high task demand. Taken together, performing demanding feature-based counting tasks interfered with differential emotion processing indexed by the EPN. The present findings demonstrate that taxing processing resources by a competing primary visual attention task markedly attenuated the early discrimination of emotional from neutral picture contents. Thus, these results provide further empirical support for an interference account of the emotion-attention interaction under conditions of competition. Previous studies revealed the interference of selective emotion processing when attentional resources were directed to locations of explicitly task-relevant stimuli. The present data suggest that interference of emotion processing by competing task demands is a more general phenomenon extending to the domain of feature-based attention. Furthermore, the results are inconsistent with the notion of effortlessness, i.e., early emotion discrimination despite concurrent task demands. These findings implicate to assess the presumed automatic nature of emotion processing at the level of specific aspects rather than considering automaticity as an all-or-none phenomenon.


Influence of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia.
Mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was used for treatment of 12 patients with moderate hypercholesterolemia, but not classical familial hypercholesterolemia. For most patients, measurements of turnover of low density lipoprotein-apolipoprotein B (LDL-apoB) were made on placebo and during treatment with two doses of mevinolin. LDL turnover was determined after injection of autologous 125I-labeled radioiodinated LDL. Compared to placebo, a low dose of mevinolin (10 mg, twice daily (BID] caused reductions of plasma total cholesterol and LDL-cholesterol averaging 15% and 20%, respectively; corresponding reductions on high doses of mevinolin (20 mg BID) were 22% and 31%, respectively. Triglyceride levels were unchanged by the drug. High density lipoprotein cholesterol levels rose significantly on the high dose, but not on the low dose. Neither dose produced a stastistically significant change in fractional catabolic rate (FCR) for LDL-apoB for the whole group, although several patients had increases in FCR on both doses. In contrast, both doses of mevinolin caused decreases in production rates of LDL-apoB. Thus, the fall in LDL levels in patients with moderate hypercholesterolemia can be explained more by a reduction in the input rate of LDL-apoB than by enhanced fractional removal of LDL from the circulation.


A temperature-based feedback control system for electromagnetic phased-array hyperthermia: theory and simulation.
A hybrid proportional-integral-in-time and cost-minimizing-in-space feedback control system for electromagnetic, deep regional hyperthermia is proposed. The unique features of this controller are that (1) it uses temperature, not specific absorption rate, as the criterion for selecting the relative phases and amplitudes with which to drive the electromagnetic phased-array used for hyperthermia and (2) it requires on-line computations that are all deterministic in duration. The former feature, in addition to optimizing the treatment directly on the basis of a clinically relevant quantity, also allows the controller to sense and react to time- and temperature-dependent changes in local blood perfusion rates and other factors that can significantly impact the temperature distribution quality of the delivered treatment. The latter feature makes it feasible to implement the scheme on-line in a real-time feedback control loop. This is in sharp contrast to other temperature optimization techniques proposed in the literature that generally involve an iterative approximation that cannot be guaranteed to terminate in a fixed amount of computational time. An example of its application is presented to illustrate the properties and demonstrate the capability of the controller to sense and compensate for local, time-dependent changes in blood perfusion rates.


Occupational physicians' perceived value of evidence-based medicine intervention in enhancing their professional performance.
This study evaluated how physicians in a nonclinical setting perceive the value of an intervention with multifaceted evidence-based medicine with regard to enhancing their professional performance. A qualitative study was conducted using focus groups and face-to-face interviews with 14 of the 48 Dutch occupational physicians who participated in the intervention. The intervention combined a didactic course in evidence-based medicine with recurrent case-method learning sessions. During the sessions, the participants were challenged to discuss their cases and to give one another feedback on how to find information on cases. Five main themes and four subthemes were identified: professional behavior and quality of care (subtheme: transparency): occupational physicians associated being up-to-date with quality of care, and evidence-based medicine was associated with improvements in professional standards; critical attitude and improved recommendations: occupational physicians asked themselves more-profound questions and searched more for information; sharing knowledge: the peer-group sessions facilitated the sharing of knowledge; communication (subthemes: colleagues, clients and other specialists): the more soundly based recommendations enhanced self-confidence positively and therefore altered interaction with medical specialists in particular; and satisfaction and barriers: the occupational physicians were especially content with the structured discussion in the peer-group sessions. However, the intervention was very time consuming. The participants regarded the intervention as a useful method for enhancing their professional performance. They stated that they became more up-to-date and more self-confident by searching for and sharing knowledge. These actions resulted in more scientifically based recommendations and improved interaction with clients and other specialists. However, time constraints remain an important barrier.


Superantigen activation of immune cells evokes epithelial (T84) transport and barrier abnormalities via IFN-gamma and TNF alpha: inhibition of increased permeability, but not diminished secretory responses by TGF-beta2.
Superantigens (SAgs) are extremely potent stimulants of T cell activity that have been implicated in the etiopathophysiology of inflammatory disease. Here, we tested the hypothesis that Staphylococcus aureus enterotoxin B (SEB), a model SAg, can alter epithelial transport and/or barrier functions via immune stimulation. Confluent monolayers of the human colonic T84 epithelial cell line, grown on filter supports, were cocultured with SEB +/- PBMC. Subsequently, T84 transport (consisting of baseline short-circuit current (Isc, indicates net ion transport) and secretory responses to carbachol and forskolin) and barrier functions (consisting of transepithelial resistance and fluxes of 3H-labeled mannitol and 51Cr-EDTA) were examined in Ussing chambers. T84 monolayers cocultured with SEB-activated PBMC displayed a time- and dose-dependent decrease in secretory responses to carbachol and forskolin and a significant increase in permeability. These dramatic changes in epithelial function were not due to reduced epithelial viability. Neutralizing Abs to IFN-gamma partially prevented the transport abnormalities, and Abs to TNF-alpha inhibited the increase in epithelial permeability. Abs to IL-1beta and IL-6 did not modulate the SEB-activated PBMC-induced T84 pathophysiology. Addition of TGF-beta2 to conditioned medium from SEB-activated PBMC partially inhibited the increase in T84 permeability but did not affect the transport abnormalities. We conclude that SAgs can elicit epithelial irregularities characteristic of enteric inflammation and that IFN-gamma and TNF-alpha are key mediators in this coculture model of epithelial dysfunction. Additionally, we would highlight the role that TGF-beta2 may play in preventing prolonged increases in epithelial permeability.


Attributable Delay of Discharge for Children with Long-Term Mechanical Ventilation.
To assess the reasons for discharge delays for children with long-term mechanical ventilation. Charts of children (0-18 years of age) with a new tracheostomy in the Pulmonary Habilitation Program at the Ann and Robert H. Lurie Children's Hospital of Chicago were retrospectively reviewed for demographic information, medical diagnoses, medical stability, discharge to home, reasons for discharge delay, and hours of staffed home nursing. All patients were discharged on mechanical ventilation. Discharge delay was defined as >10 days after medical stability. Hospital charges were analyzed and excess charges quantified beginning with the date of delay. Descriptive statistics and Pearson χ2 tests were used to compare nursing hours and demographics. Of 72 patients, 55% were male with mean age 1.8 years (SD 3.8) at tracheostomy placement. The most common long-term mechanical ventilation indication was chronic lung disease (n = 47, 65%); 54% had discharge delays, the majority were primarily due to lack of home nursing (62%), followed by delay of caregiver training (18%), caregiver health and social issues (8%), and delay in a transitional care facility bed (8%). Of the 39 delayed patients, 10% ($13 217 889) of hospital charges occurred during excess days with a median of $186 061 (IQR $117 661-$386 905) per patient. Over one-half of children discharged to the community from a large inpatient pediatric long-term mechanical ventilation program had a nonmedical delay of discharge home, most commonly because of home nurse staffing. This case series provides further evidence that limited availability of home nursing impedes efficient discharge and prolongs hospitalizations.


Agent-based models of collective intelligence.
Collective or group intelligence is manifested in the fact that a team of cooperating agents can solve problems more efficiently than when those agents work in isolation. Although cooperation is, in general, a successful problem solving strategy, it is not clear whether it merely speeds up the time to find the solution, or whether it alters qualitatively the statistical signature of the search for the solution. Here we review and offer insights on two agent-based models of distributed cooperative problem-solving systems, whose task is to solve a cryptarithmetic puzzle. The first model is the imitative learning search in which the agents exchange information on the quality of their partial solutions to the puzzle and imitate the most successful agent in the group. This scenario predicts a very poor performance in the case imitation is too frequent or the group is too large, a phenomenon akin to Groupthink of social psychology. The second model is the blackboard organization in which agents read and post hints on a public blackboard. This brainstorming scenario performs the best when there is a stringent limit to the amount of information that is exhibited on the board. Both cooperative scenarios produce a substantial speed up of the time to solve the puzzle as compared with the situation where the agents work in isolation. The statistical signature of the search, however, is the same as that of the independent search.


Multiple flap coverage for degloving hand injuries.
A technic incorporating the simultaneous elevation of multiple adjacent thoracoabdominal pedicale flaps, based in opposite directions, has been successfully used on four patients with extensive degloving injuries of the hand. In all cases, the hand was later divided into individual digits. A five-year follow-up of three patients is presented, illustrating functional results good enough to allow the patients to return to work. The special problems of a circumferential wound and digital shortening appear to be better controlled by this technic than by a single long "wrap-around" flap. Various technics of skin coverage are reviewed.


Palindrome content of the yeast Saccharomyces cerevisiae genome.
Palindromic sequences are important DNA motifs involved in the regulation of different cellular processes, but are also a potential source of genetic instability. In order to initiate a systematic study of palindromes at the whole genome level, we developed a computer program that can identify, locate and count palindromes in a given sequence in a strictly defined way. All palindromes, defined as identical inverted repeats without spacer DNA, can be analyzed and sorted according to their size, frequency, GC content or alphabetically. This program was then used to prepare a catalog of all palindromes present in the chromosomal DNA of the yeast Saccharomyces cerevisiae. For each palindrome size, the observed palindrome counts were significantly different from those in the randomly generated equivalents of the yeast genome. However, while the short palindromes (2-12 bp) were under-represented, the palindromes longer than 12 bp were over-represented, AT-rich and preferentially located in the intergenic regions. The 44-bp palindrome found between the genes CDC53 and LYS21 on chromosome IV was the longest palindrome identified and contained only two C-G base pairs. Avoidance of coding regions was also observed for palindromes of 4-12 bp, but was less pronounced. Dinucleotide analysis indicated a strong bias against palindromic dinucleotides that could explain the observed short palindrome avoidance. We discuss some possible mechanisms that may influence the evolutionary dynamics of palindromic sequences in the yeast genome.


Exploring the diffusion of molecular oxygen in the red fluorescent protein mCherry using explicit oxygen molecular dynamics simulations.
The development of fluorescent proteins (FPs) has revolutionized cell biology research. The monomeric variants of red fluorescent proteins (RFPs), known as mFruits, have been especially valuable for tagging and tracking cellular processes in vivo. Determining oxygen diffusion pathways in FPs can be important for improving photostability and for understanding maturation of the chromophore. We use molecular dynamics (MD) calculations to investigate the diffusion of molecular oxygen in one of the most useful monomeric RFPs, mCherry. We describe a pathway that allows oxygen molecules to enter from the solvent and travel through the protein barrel to the chromophore. We calculate the free-energy of an oxygen molecule at points along the path. The pathway contains several oxygen hosting pockets, which are identified by the amino acid residues that form the pocket. We also investigate an RFP variant known to be significantly less photostable than mCherry and find much easier oxygen access in this variant. The results provide a better understanding of the mechanism of molecular oxygen access into the fully folded mCherry protein barrel and provide insight into the photobleaching process in these proteins.


Bayesian space-time analysis of Echinococcus multilocularis-infections in foxes.
A total of 26,220 foxes that were hunted or found dead in Thuringia, Germany, between 1990 and 2009 were examined for infection with Echinococcus multilocularis, the causative agent of human alveolar echinococcosis, and 6853 animals were found infected. The available data on the foxes including the location (local community; district) and the date of hunting/death were analyzed using a hierarchical Bayesian space-time model. The distribution of the model parameters and their variability was estimated on the basis of the sample size, the number of cases per spatial unit and time interval, and an adjacency matrix of the municipalities using a Markov Chain Monte Carlo simulation technique to assess the spatial and temporal changes in the distribution of the parasite. The model used to evaluate the data is widely applicable and can be applied to analyse data sets with gaps and variable sample sizes per spatial and temporal unit. In the study area, the prevalence of E. multilocularis increased from 11.9% (95% confidence interval 9.9-14.0%) in 1990 to 42.0% (39.1-44.1%) in 2005. While the infection was present in foxes only in the north-western parts of Thuringia in 1990, it had spread over the entire state by 2004. These results demand increased vigilance for human alveolar echinococcosis in Thuringia.


Phenytoin and formation of T lymphocyte rosettes.
Phenytoin sodium has been associated with the formation of altered T lymphocyte rosettes in vitro. To investigate the clinical relevance of this observation, the formation of T lymphocyte rosettes in nine patients was studied before treatment with phenytoin and after therapeutic concentrations of the drug in plasma were attained. The percentage of total rosette-forming cells found before treatment was not significantly different from the percentage found 24 hours after treatment. Likewise, the percentage of active rosette-forming cells before phenytoin therapy was not significantly less than after therapy. These results suggest that in vivo treatment with phenytoin does not acutely inhibit the formation of T lymphocyte rosettes.


Tumor-to-tumor metastasis: breast carcinoma to meningioma.
Metastasis of breast carcinoma to meningioma is a rare phenomenon with relatively few reports in the literature, although it is the most common type of carcinoma-to-meningioma metastasis. Several factors have been implicated in the pathogenesis of these lesions, including the microenvironment and vascular network of the meningioma, expression of cell-cell adhesion molecules, local immunosuppression, and hormonal factors, including estrogen and progesterone, whose receptors have been well-characterized in these two tumor types. While histopathologic study is the cornerstone of diagnosis of these lesions, newer radiological modalities such as magnetic resonance spectroscopy and perfusion MRI have shown promise, particularly in screening patients at risk for developing these lesions. Because their detection is problematic, it is imperative that clinicians thoroughly examine tissue samples of resected meningiomas, as this may alter the patient's treatment plan and prognosis. Furthermore, as both of these neoplasms often co-occur in women with breast cancer, clinicians should be vigilant of the potential for intrameningioma metastasis when neurological involvement becomes apparent in late-stage disease. While these unusual lesions should be managed surgically, as with meningiomas, it is unclear whether proposed adjuvants such as hormonal and radiation therapy improve survival.


Extremely Low-Volume Burpee Interval Training Equivalent to 8 Minutes Per Session Improves Vertical Jump Compared with Sprint Interval Training in Real-World Circumstances.
Pérez-Ifrán, P, Magallanes, CA, de S. Castro, FA, Astorino, TA, and Benítez-Flores, S. Extremely low-volume burpee interval training equivalent to 8 minutes per session improves vertical jump compared with sprint interval training in real-world circumstances. J Strength Cond Res 38(1): 10-20, 2024-The aim of this study was to compare the cardiometabolic and physical effects of 2 time-matched high-intensity programs in a real-world environment. Forty-three active and healthy adults (sex = 31 men and 12 women; age = 27 ± 5 years; peak heart rate [HR peak ] = 190.7 ± 10.6 beat·min -1 ) were randomized to 2 very low-volume protocols (∼8 minutes): sprint interval training (SIT) ( n = 15), burpee interval training (BIT) ( n = 15), and control (CON) ( n = 13). Subjects in SIT and BIT performed 5 days of 10 × 4 second "all-out" efforts with 30 seconds of recovery. Body composition, blood pressure, countermovement jump (CMJ), 10-m sprint, shuttle run test (SRT), autonomic modulation , self-efficacy, and intention were evaluated before and after training. Sprint interval training elicited a higher %HR peak , energy expenditure, rating of perceived exertion category ratio 10 scale, and feeling scale than BIT ( p < 0.05). SRT distance was significantly improved in SIT ( p = 0.03, d = 0.62), whereas CMJ height was significantly enhanced in BIT ( p = 0.0014, d = 0.72). Self-efficacy progressively worsened for SIT than for BIT as sessions increased, and significant differences were found in 5× a week frequency between protocols ( p = 0.040, d = 0.79). No differences in intention to engage were detected between the regimens ( p > 0.05). No changes were observed in body composition, blood pressure, 10-m sprint, SRTV̇O 2max , or autonomic variables with training ( p > 0.05). Results exhibit that extremely low-volume SIT improved running performance, whereas BIT increased the vertical jump.


A nonstructural polypeptide encoded by immediate-early transcription unit 1 of murine cytomegalovirus is recognized by cytolytic T lymphocytes.
We have constructed target cells by cotransfection of the MHC gene Ld and fragments of murine cytomegalovirus (MCMV) DNA coding for nonstructural immediate-early (IE) proteins. Transfectants were tested by using CTL clone IE1 with specificity for an IE epitope presented in association with Ld. Data show that clone IE1 recognizes a product of the ie1 transcription unit of MCMV, and that its specificity is shared by approximately 25% of polyclonal IE-specific CTL. The results provide the first definite evidence that expression of a herpes virus IE gene encoding a regulatory protein gives rise to antigen expression detectable by specific CTL.


Synaptic and nonsynaptic plasticity approximating probabilistic inference.
Learning and memory operations in neural circuits are believed to involve molecular cascades of synaptic and nonsynaptic changes that lead to a diverse repertoire of dynamical phenomena at higher levels of processing. Hebbian and homeostatic plasticity, neuromodulation, and intrinsic excitability all conspire to form and maintain memories. But it is still unclear how these seemingly redundant mechanisms could jointly orchestrate learning in a more unified system. To this end, a Hebbian learning rule for spiking neurons inspired by Bayesian statistics is proposed. In this model, synaptic weights and intrinsic currents are adapted on-line upon arrival of single spikes, which initiate a cascade of temporally interacting memory traces that locally estimate probabilities associated with relative neuronal activation levels. Trace dynamics enable synaptic learning to readily demonstrate a spike-timing dependence, stably return to a set-point over long time scales, and remain competitive despite this stability. Beyond unsupervised learning, linking the traces with an external plasticity-modulating signal enables spike-based reinforcement learning. At the postsynaptic neuron, the traces are represented by an activity-dependent ion channel that is shown to regulate the input received by a postsynaptic cell and generate intrinsic graded persistent firing levels. We show how spike-based Hebbian-Bayesian learning can be performed in a simulated inference task using integrate-and-fire (IAF) neurons that are Poisson-firing and background-driven, similar to the preferred regime of cortical neurons. Our results support the view that neurons can represent information in the form of probability distributions, and that probabilistic inference could be a functional by-product of coupled synaptic and nonsynaptic mechanisms operating over several timescales. The model provides a biophysical realization of Bayesian computation by reconciling several observed neural phenomena whose functional effects are only partially understood in concert.


Complex Management of Nephrotic Syndrome and Kidney Failure during Pregnancy in a Type 1 Diabetes Patient: A Challenging Case.
Pregnancy with chronic kidney disease is challenging, and patients with diabetic nephropathy are at particular risk of a rapid kidney function decline during pregnancy. While indications for the management of pregnant patients with initial diabetic nephropathy are widely available in the literature, data on patients with severe nephrotic syndrome and kidney function impairment are lacking, and the decision on whether and when dialysis should be initiated is not univocal. We report a type 1 diabetes patient who started pregnancy with a severe nephrotic syndrome and shifted from CKD stage 3b to stage 5 during pregnancy. The management was complicated by a fetal heart malformation and by poorly controlled diabetes. The evidence for and against starting dialysis was carefully evaluated, and the choice of strict nephrological and obstetrical monitoring, nutritional management, and diuretic treatment made it possible to avoid dialysis in pregnancy, after ruling out pre-eclampsia. This experience enables examination of some open issues and contributes to the discussion of when to start dialysis in pregnancy.


A metabolomics approach for predicting the response to neoadjuvant chemotherapy in cervical cancer patients.
Cervical cancer is a clinical and pathological heterogeneity disease, which requires different types of treatments and leads to a variety of outcomes. In clinical practice, only some patients benefit from chemotherapy treatment. Identifying patients who will be responsive to chemotherapy could increase their survival time, which has important implications in personalized treatment and outcomes, while identifying non-responders may reduce the likelihood for these patients to receive ineffective treatment and thereby enable them to receive other potentially effective treatments. Plasma metabolite profiling was performed in this study to identify the potential biomarkers that could predict the response to neoadjuvant chemotherapy (NACT) for cervical cancer patients. The metabolic profiles of plasma from 38 cervical cancer patients with a complete, partial and non-response to NACT were studied using a combination of liquid chromatography coupled with mass spectrometry (LC/MS) and multivariate analysis methods. L-Valine and L-tryptophan were finally identified and verified as the potential biomarkers. A prediction model constructed with L-valine and L-tryptophan correctly identified approximately 80% of patients who were non-response to chemotherapy and 87% of patients who were had a pathologically complete response to chemotherapy. The model has an excellent discriminant performance with an AUC of 0.9407. These results show promise for larger studies that could produce more personalized treatment protocols for cervical cancer patients.


The V3-directed immune response in natural human immunodeficiency virus type 1 infection is predominantly directed against a variable, discontinuous epitope presented by the gp120 V3 domain.
The specific binding of antibodies to the V3 loop in sera from human immunodeficiency type 1 (HIV-1)-infected individuals was investigated. Different V3 structures were analyzed as full-length loops or by pepscan. Our data show that on full-length V3 loops, both variable regions on either side of the tip of the loop (GPGRAF) contribute to a common epitope for type-specific antibodies. Type-specific antibodies bound strongly and at high titers to native V3 loops but negligibly once the loop was denatured. In contrast to the type-specific, discontinuous epitope, the linear, conserved epitopes presented by the full-length V3 loop, the tip, the amino-terminal base, and the carboxy-terminal base were not accessible to serum antibody. When the V3 sequences were analyzed with linear peptides, antibodies bound preferentially to peptides containing the conserved GPGRAF sequence. Thus, two different specificities of V3-directed antibodies were detected in patient sera. Unlike group-specific antibodies directed against GPGRAF peptides, lack of type-specific antibodies directed against the discontinuous epitope was correlated with viral escape from autologous neutralization. Our data suggest that the full-length conformation of the V3 loop is accessible predominantly to highly type-specific antibodies present in sera from HIV-1-infected individuals. These antibodies are directed against discontinuous V3 epitopes, not against conserved linear V3 targets. The implications of these findings for viral escape and blockade of infection with V3-based vaccines are discussed.


Quantitative HPLC analysis of acids in Brazilian cachaças and various spirits using fluorescence detection of their 9-anthrylmethyl esters.
An analytical procedure for the separation and quantification of 17 short-chain, medium-chain, and long-chain acids in cachaças and various spirits has been developed involving C18 solid phase extraction, derivatization with 9-anthryldiazomethane, and reverse phase HPLC using fluorescence detection. The limit of detection was between 5 and 15 fmol, whereas the recovery of nonanoic acid as internal standard was >95%. Relative standard deviation values for reproducibility were between 0.09 and 20.4%, and repeatability was between 0.05 and 11.3%.


[Kynurenines in pathogenesis of endogenous psychiatric disorders].
The essential amino acid tryptophan is metabolized on the methoxyindole pathway to serotonin, melatonin and 5-hydroxyindoleacetic acid and on the kynurenine pathway to kynurenine and related neuroactive metabolites, including 3-hydroxykynurenine, kynurenic acid, quinolinic acid and xanthurenic acid. Kynurenine and related metabolites play a significant role in the pathogenesis of major depressive disorder and schizophrenia. This paper is the review of literature data on the most modern state of this problem.


Preparation of nanocellulose and its applications in wound dressing: A review.
Nanocellulose, as a nanoscale polymer material, has garnered significant attention worldwide due to its numerous advantages including excellent biocompatibility, thermal stability, non-toxicity, large specific surface area, and good hydrophilicity. Various methods can be employed for the preparation of nanocellulose. Traditional approaches such as mechanical, chemical, and biological methods possess their own distinct characteristics and limitations. However, with the growing deterioration of our living environment, several green and environmentally friendly preparation techniques have emerged. These novel approaches adopt eco-friendly technologies or employ green reagents to achieve environmental sustainability. Simultaneously, there is a current research focus on optimizing traditional nanocellulose preparation methods while addressing their inherent drawbacks. The combination of mechanical and chemical methods compensates for the limitations associated with using either method alone. Nanocellulose is widely used in wound dressings owing to its exceptional properties, which can accelerate the wound healing process and reduce patient discomfort. In this paper, the principle, advantages and disadvantages of each preparation method of nanocellulose and the research findings in recent years are introduced Moreover, this review provides an overview of the utilization of nanocellulose in wound dressing applications. Finally, the prospective trends in its development alongside corresponding preparation techniques are discussed.