Inflammatory myofibroblastic tumors: A short series with an emphasis on the diagnostic and therapeutic challenges.

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are a distinct entity of mesenchymal tumors. We present the challenges in their diagnosis and management. MATERIALS AND METHODS: A retrospective study with detailed clinical, radiological, and histopathological (HPE) features along with management and outcome of 10 biopsy-proven patients with IMT, between 2001 and 2020. RESULTS: The location included intracranial (5), orbital (4), and spinal (1) with M : F = 7 : 3. The mean age of onset was in the third decade. The commonest symptom was headache, while proptosis and blurred vision occurred in orbital IMTs. HPE revealed diffuse infiltration of mixed inflammatory cells over proliferating myofibroblasts. Smooth muscle antigen immunoreactivity was noted in fibroblastic spindle cells of all IMTs. However, we did not find anaplastic lymphoma kinase expression in any of our cases, as this is only found in ~ 50% of all IMTs. Tumor infiltration into adjacent tissue was noted in 4 patients. Surgical excision was limited to orbital IMTs, as most central nervous system (CNS) tumors were not amenable for resection. Steroid administration showed moderate improvement in the IMT-CNS patients but also required additional immunomodulation. Four patients had a median long-term follow-up of 7 years. Two patients had recurrent lesions demonstrated by imaging after 2 years of initial presentation. CONCLUSION: IMTs are rare and ambiguous tumors of unknown etiology that can occur anywhere in the body. Clinical and radiological features may not be specific to determine the diagnosis, but it should be considered as a differential diagnosis. Extensive thorough workup with histopathology along with the help of immunohistochemistry is conducive to better clinical outcomes. Surgical biopsy with extensive and total resection of these tumors along with steroid and radiotherapy may enhance the survival outcomes.

Functional parcellation of mouse visual cortex using statistical techniques reveals response-dependent clustering of cortical processing areas.

The visual cortex of the mouse brain can be divided into ten or more areas that each contain complete or partial retinotopic maps of the contralateral visual field. It is generally assumed that these areas represent discrete processing regions. In contrast to the conventional input-output characterizations of neuronal responses to standard visual stimuli, here we asked whether six of the core visual areas have responses that are functionally distinct from each other for a given visual stimulus set, by applying machine learning techniques to distinguish the areas based on their activity patterns. Visual areas defined by retinotopic mapping were examined using supervised classifiers applied to responses elicited by a range of stimuli. Using two distinct datasets obtained using wide-field and two-photon imaging, we show that the area labels predicted by the classifiers were highly consistent with the labels obtained using retinotopy. Furthermore, the classifiers were able to model the boundaries of visual areas using resting state cortical responses obtained without any overt stimulus, in both datasets. With the wide-field dataset, clustering neuronal responses using a constrained semi-supervised classifier showed graceful degradation of accuracy. The results suggest that responses from visual cortical areas can be classified effectively using data-driven models. These responses likely reflect unique circuits within each area that give rise to activity with stronger intra-areal than inter-areal correlations, and their responses to controlled visual stimuli across trials drive higher areal classification accuracy than resting state responses.

Signal-to-signal neural networks for improved spike estimation from calcium imaging data.

Spiking information of individual neurons is essential for functional and behavioral analysis in neuroscience research. Calcium imaging techniques are generally employed to obtain activities of neuronal populations. However, these techniques result in slowly-varying fluorescence signals with low temporal resolution. Estimating the temporal positions of the neuronal action potentials from these signals is a challenging problem. In the literature, several generative model-based and data-driven algorithms have been studied with varied levels of success. This article proposes a neural network-based signal-to-signal conversion approach, where it takes as input raw-fluorescence signal and learns to estimate the spike information in an end-to-end fashion. Theoretically, the proposed approach formulates the spike estimation as a single channel source separation problem with unknown mixing conditions. The source corresponding to the action potentials at a lower resolution is estimated at the output. Experimental studies on the spikefinder challenge dataset show that the proposed signal-to-signal conversion approach significantly outperforms state-of-the-art-methods in terms of Pearson's correlation coefficient, Spearman's rank correlation coefficient and yields comparable performance for the area under the receiver operating characteristics measure. We also show that the resulting system: (a) has low complexity with respect to existing supervised approaches and is reproducible; (b) is layer-wise interpretable, and (c) has the capability to generalize across different calcium indicators.

[Diabetes mellitus and high blood pressure over risk in HIV-infected people followed at Souro Sanou University Hospital Day Hospital, Bobo-Dioulasso 2018]. / Sur-risque de diabète sucré et d'hypertension artérielle chez les personnes infectées par le VIH suivies à l'hôpital de jour du CHU Souro Sanou, Bobo-Dioulasso, Burkina Faso, 2018.

BACKGROUND: Non-communicable diseases (NCDs) represent the leading causes of death worldwide. HIV also increases the risk of developing NCDs including diabetes mellitus and hypertension. METHODS: A cross-sectional study, based on an analysis of the cohort database of the day hospital of the Souro Sanou teaching hospital in Bobo-Dioulasso (Burkina Faso). Diabetes mellitus was defined by the undergoing of anti-diabetic treatment or two successive measurements of fasting blood sugar above 7mmol/l and high blood pressure by the undergoing of antihypertensive treatment or two successive measurements of blood pressure above 140/90mmHg. Comparison of the frequency of diabetes and hypertension in the people living with HIV/AIDS (PLWHA) population on antiretroviral therapy (ART) with that of the general population of Burkina Faso was made by indirect standardization according to age and gender. RESULTS: A total of 4259 patients including 3148 women (73.9%) were included in this study. The median age of the patients was 45 years (IQR: 38-52); the median body mass index (BMI) was 19.6kg/m2 (IQR: 15.4 - 22.7) and 48.3% of patients had a BMI≥25kg/m2. The median CD4 count was 590 cells/mm3 (IQR: 417-785). The median ART duration was 8.2 years (IQR: 4.7-11.2). The majority of patients (82.9%) were on treatment combinations consisting in 2 INTI+1 NNRTI. Prevalence of hypertension was 39.8%; it was statistically higher in men than in women (45.8% versus 37.8%). Prevalence of hypertension was 87.0% higher in the PLWHA population than among same-sex and same-age subjects in the general population. Prevalence of diabetes mellitus was 7.3%. Diabetes mellitus was more common in men than in women (10.1% versus 6.3%; P<10-3). Prevalence of diabetes mellitus was 36.0% higher in the PLWHA population than among same-sex and same-age subjects in the general population. CONCLUSION: Prevalence of diabetes mellitus and hypertension was higher among PLHWA undergoing ART than in the general population. Care for the PLHWA population should more widely include NCD treatment.

Data-driven measurement of precision of components of pitch curves in Carnatic music.

Carnatic music (CM) is characterized by continuous pitch variations called gamakas, which are learned by example. Precision is measured on the points of zero-slope in gamaka- and non-gamaka-segments of the pitch curve as the standard deviation (SD) of the error in their pitch with respect to targets. Two previous techniques are considered to identify targets: the nearest semitone and the most likely mean of a semi-continuous Gaussian mixture model. These targets are employed irrespective of where the points of zero-slope occur in the pitch curve. The authors propose segmenting CM pitch curves into non-overlapping components called constant-pitch notes (CPNs) and stationary points (STAs), i.e., points where the pitch curve outside the CPNs changes direction. Targets are obtained statistically from the histograms of the mean pitch-values of CPNs, anchors (CPNs adjacent to STAs), and STAs. The upper and lower quartiles of SDs of errors in long CPNs (9-15 cents), short CPNs (20-26 cents), and STAs (41-54 cents) are separable, which justifies the component-wise treatment. The CPN-STA model also brings out a hitherto unreported structure in ragas and explains the precision obtained using the previous techniques.

Spike Estimation from Fluorescence Signals Using High-Resolution Property of Group Delay.

Spike estimation from calcium (Ca2+) fluorescence signals is a fundamental and challenging problem in neuroscience. Several models and algorithms have been proposed for this task over the past decade. Nevertheless, it is still hard to achieve accurate spike positions from the Ca2+ fluorescence signals. While existing methods rely on data-driven methods and the physiology of neurons for modelling the spiking process, this work exploits the nature of the fluorescence responses to spikes using signal processing. We first motivate the problem by a novel analysis of the high-resolution property of minimum-phase group delay (GD) functions for multi-pole resonators. The resonators could be connected either in series or in parallel. The Ca2+ indicator responds to a spike with a sudden rise, that is followed by an exponential decay. We interpret the Ca2+ signal as the response of an impulse train to the change in Ca2+ concentration, where the Ca2+ response corresponds to a resonator. We perform minimum-phase group delay-based filtering of the Ca2+ signal for resolving spike locations. The performance of the proposed algorithm is evaluated on nine datasets spanning various indicators, sampling rates and, mouse brain regions. The proposed approach: GDspike, is compared with other spike estimation methods including MLspike, Vogelstein de-convolution algorithm, and data-driven Spike Triggered Mixture (STM) model. The performance of GDSpike is superior to that of the Vogelstein algorithm and is comparable to that of MLSpike. It can also be used to post-process the output of MLSpike, which further enhances the performance.

17ß-Hydroxy-18-acetoxywithanolides from Aeroponically Grown Physalis crassifolia and Their Potent and Selective Cytotoxicity for Prostate Cancer Cells.

When cultivated under aeroponic growth conditions, Physalis crassifolia produced 11 new withanolides (1-11) and seven known withanolides (12-18) including those obtained from the wild-crafted plant. The structures of the new withanolides were elucidated by the application of spectroscopic techniques, and the known withanolides were identified by comparison of their spectroscopic data with those reported. Withanolides 1-11 and 16 were evaluated for their potential anticancer activity using five tumor cell lines. Of these, the 17ß-hydroxy-18-acetoxywithanolides 1, 2, 6, 7, and 16 showed potent antiproliferative activity, with some having selectivity for prostate adenocarcinoma (LNCaP and PC-3M) compared to the breast adenocarcinoma (MCF-7), non-small-cell lung cancer (NCI-H460), and CNS glioma (SF-268) cell lines used. The cytotoxicity data obtained for 12-15, 17, and 19 have provided additional structure-activity relationship information for the 17ß-hydroxy-18-acetoxywithanolides.

Development and evaluation of buccoadhesive tablet for selegiline hydrochloride based on thiolated polycarbophil.

Selegiline hydrochloride (SHCl), a monoamine oxidase B inhibitor, is used as an adjunct in the therapy of Parkinson's disease. This study is concerned with the preparation and evaluation of mucoadhesive buccal tablet for controlled systemic delivery of SHCl. Buccal absorption of selegiline can bypass its first-pass metabolism and improve bioavailability accompanied by greatly reduced metabolite formation, which is potentially of enhanced therapeutic value in patients with Parkinson's disease. Polycarbophil-cysteine (PCP-cys) conjugate, which is a thiolated derivative of the mucoadhesive polymer polycarbophil, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride-mediated amide bond coupling. Tablets of SHCl based on native and thiolated polycarbophil were prepared. The prepared tablets were evaluated for drug content, swelling behavior, mucoadhesive strength, in vitro drug release, ex vivo permeation and in vitro cytotoxicity. PCP-cys tablets showed enhanced mucoadhesion and retarded drug release compared to polycarbophil tablets. Permeation data of SHCl from matrices prepared using the PCP-cys polymer revealed a significantly higher value of apparent permeability in comparison to polycarbophil, which supported the information in literature that thiolation imparts permeation enhancing properties to mucoadhesive polymers. In vitro cytotoxicity studies on PCP-cys using L-929 mouse fibroblast cell line indicated that conjugation with cysteine does not impart any apparent toxicity to polycarbophil. The results from the study indicate that the buccal delivery of SHCl using thiolated polycarbophil tablet could provide a way for improved therapy of Parkinson's disease.

Design and characterization of chitosan-alginate microspheres for ocular delivery of azelastine.

The use of mucoadhesive biopolymers is one of the best approaches to prolong the drug residence inside the cul-de-sac, consequently increasing the bioavailability. Thus, the focus of this work was to develop mucoadhesive microspheres to overcome the limitations of ocular drug delivery. The chitosan-sodium alginate microspheres of azelastine hydrochloride were fabricated using modified ionotropic gelation technique. The particle size, zeta potential, entrapment efficiency and drug release kinetics were evaluated and characterized by SEM, FT-IR, DSC, in vitro mucoadhesion and in vivo study. The microspheres had average particle size in the range of 3.55 to 6.70 µm and zeta potential +24.55 to +49.56 mV. The fabricated microspheres possess maximum drug entrapment of 73.05% with 65% mucin binding efficiency and revealed a controlled release over the 8-h period following a non-Fickian diffusion. SEM showed that microspheres were distinct solid with irregular shape. FT-IR and DSC results concluded the drug entrapment into microspheres. In vivo studies on ocular rat model revealed that azelastine microspheres had better efficacy. Chitosan sodium alginate microspheres prepared were in particle size range suitable for ocular purpose. In vitro release and in vivo efficacy studies revealed that the microspheres were effective in prolonging the drug's presence in cul de sac with improved therapeutic efficacy.

Implementation of the WHO core components of an infection prevention and control programme in two sub-saharan African acute health-care facilities: a mixed methods study.

BACKGROUND: The coronavirus pandemic again highlighted the need for robust health care facility infection prevention and control (IPC) programmes. WHO guidelines on the core components (CCs) of IPC programmes provides guidance for facilities, but their implementation can be difficult to achieve in resource-limited settings. We aimed to gather evidence on an initial WHO IPC implementation experience using a mixed methods approach. METHODS: A five-day training on the WHO IPC CCs was conducted at two reference acute health care facilities in the Democratic Republic of Congo and Burkina Faso. This was accompanied by a three-part mixed-methods evaluation consisting of a: (1) baseline and follow-up survey of participants' knowledge, attitudes and practices (KAP), (2) qualitative assessment of plenary discussion transcripts and (3) deployment of the WHO IPC assessment framework (IPCAF) tool. Results were analysed descriptively and with a qualitative inductive thematic approach. RESULTS: Twenty-two and twenty-four participants were trained at each facility, respectively. Baseline and follow-up KAP results suggested increases in knowledge related to the necessity of a dedicated IPC focal person and annual evaluations of IPC training although lack of recognition on the importance of including hospital leadership in IPC training and hand hygiene monitoring recommendations remained. Most participants reported rarely attending IPC meetings or participating in IPC action planning although attitudes shifted towards stronger agreement with the feeling of IPC responsibility and importance of an IPC team. A reocurring theme in plenary discussions was related to limited resources as a barrier to IPC implementation, namely lack of reliable water access. However, participants recognised the importance of IPC improvement efforts such as practical IPC training methods or the use of data to improve quality of care. The facilities' IPCAF scores reflected a 'basic/intermediate' IPC implementation level. CONCLUSIONS: The training and mixed methods evaluation revealed initial IPC implementation experiences that could be used to inform stepwise approaches to facility IPC improvement in resource-limited settings. Implementation strategies should consider both global standards such as the WHO IPC CCs and specific local contexts. The early involvement of all relevant stakeholders and parallel efforts to advocate for sufficient resources and health system infrastructure are critical.

A history of being prescribed controlled substances and risk of drug overdose death.

OBJECTIVE: The abuse of prescription drugs has increased dramatically since 1990. Persons who overdose on such drugs frequently consume large doses and visit multiple providers. The risk of fatal overdose for different patterns of use of opioid analgesics and sedative/hypnotics has not been fully quantified. DESIGN: Matched case-control study. Cases were 300 persons who died of unintentional drug overdoses in New Mexico during 2006-2008, and controls were 5,993 patients identified through the state prescription monitoring program with matching 6-month exposure periods. OUTCOME MEASURES: Death from drug overdose or death from opioid overdose. Exposures were demographic variables and characteristics of prescription history. Crude and adjusted odds ratios (AOR) were calculated. RESULTS: Increased risk was associated with male sex (AOR 2.4, 95% confidence interval [CI] 1.8-3.1), one or more sedative/hypnotic prescriptions (AOR 3.0, CI 2.2-4.2), greater age (AOR 1.3, CI 1.2-1.4 for each 10-year increment), number of prescriptions (AOR 1.1, CI 1.1-1.1 for each additional prescription), and a prescription for buprenorphine (AOR 9.5, CI 3.0-30.0), fentanyl (AOR 3.5, CI 1.7-7.0), hydromorphone (AOR 3.3, CI 1.4-7.5), methadone (AOR 4.9, CI 2.5-9.6), or oxycodone (AOR 1.9, CI 1.4-2.6). Patients receiving a daily average of >40 morphine milligram equivalents had an OR of 12.2 (CI 9.2-16.0). CONCLUSIONS: Patients being prescribed opioid analgesics frequently or at high dosage face a substantial overdose risk. Prescription monitoring programs might be the best way for prescribers to know their patients' prescription histories and accurately assess overdose risk.

Eudragit RL100 based microspheres for ocular administration of azelastine hydrochloride.

In the present study, potential of polymeric microspheres for treatment of allergic conjunctivitis was investigated. Azelastine hydrochloride loaded Eudragit RL100 microspheres were prepared by solvent evaporation technique. The change in drug-polymer ratio on the particle size, zeta potential, entrapment efficiency and in vitro drug release was investigated. As Eudragit concentration ranged from 40 to 80 mg/ml the size range obtained was 4.18-7.36 µm with positive zeta potential. With the increase in drug polymer ratio, the entrapment efficiency was increased with maximum 14.56%. In vitro release studies demonstrated prolonged release of the drug over the period of 6 hr. Scanning electron micrographs showed that microspheres were spherical with distinct solid dense structure. Fourier transform infrared and differential scanning calorimetry studies concluded slight change in peak intensities of drug in microspheres. In vivo studies in rat model indicated that reduction in eosinophil count number was more pronounced in azelastine hydrochloride microspheres than marketed formulation, Azelast®.

Prescription drug monitoring programs and death rates from drug overdose.

OBJECTIVE: Drug overdoses resulting from the abuse of prescription opioid analgesics and other controlled substances have increased in number as the volume of such drugs prescribed in the United States has grown. State prescription drug monitoring programs (PDMPs) are designed to prevent the abuse of such drugs. This study quantifies the relation of PDMPs to rates of death from drug overdose and quantities of opioid drugs distributed at the state level. DESIGN: Observational study of the United States during 1999-2005. OUTCOME MEASURES: Rates of drug overdose mortality, opioid overdose mortality, and opioid consumption by state. RESULTS: PDMPs were not significantly associated with lower rates of drug overdose or opioid overdose mortality or lower rates of consumption of opioid drugs. PDMP states consumed significantly greater amounts of hydrocodone (Schedule III) and nonsignificantly lower amounts of Schedule II opioids. The increases in overdose mortality rates and use of prescription opioid drugs during 1999-2005 were significantly lower in three PDMP states (California, New York, and Texas) that required use of special prescription forms. CONCLUSIONS: While PDMPs are potentially an important tool to prevent the nonmedical use of prescribed controlled substances, their impact is not reflected in drug overdose mortality rates. Their effect on overall consumption of opioids appears to be minimal. PDMP managers need to develop and test ways to improve the use of their data to affect the problem of prescription drug overdoses.

[Factors associated with the occurrence of acute respiratory distress and death in patients with COVID-19 in Burkina Faso]. / Facteurs associés à la survenue de la détresse respiratoire aiguë et au décès chez des patients atteints de COVID-19 au Burkina Faso.

INTRODUCTION: The development of acute respiratory distress syndrome indicates a serious form of COVID-19. Although there have been several studies on the prognostic factors of its severe form, no such study has been conducted in Burkina Faso. METHODS: This was a retrospective cohort study conducted from March 9 to June 9, 2020 in Ouagadougou, Burkina Faso which involved 456 patients with COVID-19. RESULTS: Nearly a quarter of the patients (23.2%) had presented with acute respiratory distress and 44.3% of them died. Being over 65 years old (HR: 2.7; 95% CI: 1.5-5.1) and having hypertension (HR: 1.9; 95% CI: 1-3.5) were independently associated with the risk of mortality. However, after adjustment, only age over 65 years (HR: 2.3; 95% CI: 1.2-4.3) was a risk factor for death. The survival rate for patients over 65 was 38.5% at 7 days and 30.3% at 15 days. CONCLUSIONS: Acute respiratory distress leading to death is mainly found in older people with COVID-19. Close monitoring of these high-risk patients may reduce the risk of death.

Time Warping Solutions for Classifying Artifacts in EEG.

The most common brain-computer interface (BCI) devices use electroencephalography (EEG). EEG signals are noisy owing to the presence of many artifacts, namely head movement, and facial movements like eye blinks or jaw movements. Removal of these artifacts from EEG signals is essential for the success of any downstream BCI application. These artifacts influence different sensors of the EEG. In this paper, we devise algorithms for detection and classification of artifacts. Classification of artifacts into head nod, jaw movement and eye-blink is performed using two different varieties of time warping; namely, linear time warping, and dynamic time warping. The average accuracy of 85% and 90% is obtained using the former, and the later, respectively.

Subspace techniques for task-independent EEG person identification.

There has been a growing interest in studying electroencephalography signals (EEG) as a possible biometric. The brain signals captured by EEG are rich and carry information related to the individual, tasks being performed, mental state, and other channel/measurement noise due to session variability and artifacts. To effectively extract person-specific signatures present in EEG, it is necessary to define a subspace that enhances the biometric information and suppresses other nuisance factors. i-vector and x-vector are state-of-art subspace techniques used in speaker recognition. In this paper, novel modifications are proposed for both frameworks to project person-specific signatures from multi-channel EEG into a subspace. The modified i-vector and x-vector systems outperform baseline i-vector and x-vector systems with an absolute improvement of 10.5% and 15.9%, respectively.

Level-wise Subject adaptation to improve classification of motor and mental EEG tasks.

Classification of various cognitive and motor tasks using electroencephalogram (EEG) signals is necessary for building Brain Computer Interfaces (BCI) that are noninvasive. However, achieving high classification accuracy in a multi-subject multitask scenario is a challenge. A noticeable reduction in accuracy is observed when the subjects between train and test are mismatched. Drawing a similarity from speaker adaptation approaches in speech, we propose a method to perform subject-wise adaptation of EEG in order to improve the task classification performance. A Common Spatial Pattern (CSP) approach is employed for feature extraction. Gaussian Mixture Model (GMM) based subject-specific models are built for each of the tasks. Maximum a-posterior (MAP) adaptation is performed, and an absolute improvement of 1.22-7.26% is observed in the average accuracy.

Formulation and evaluation of microemulsion based delivery system for amphotericin B.

The present studies were designed to develop a formulation of amphotericin B in a lipid-based preparation as a microemulsion and to compare its toxicity with the commercial formulation Fungizone. The final product developed is a lyophilized amphotericin B, oil and surfactant blend for reconstitution in water to yield a microemulsion containing 5 mg/ml of the drug. Pseudoternary phase diagrams were constructed to identify areas of existence of microemulsion composed of Peceol (glyceryl monooleate) as oil phase and Mys 40 (polyethylene glycol 40 stearate) and Solutol HS 15 (polyethylene glycol 15 hydroxy stearate) as surfactants. Amphotericin B was co-evaporated with oil - surfactant mixture to produce a microemulsion pre-concentrate. The co-evaporate was diluted in water, filtered for sterilization and lyophilized to obtain the final product. The lyophilized as well as the reconstituted products were separately studied for stability and the latter was also characterized for various physicochemical aspects including droplet size of the dispersed phase, osmolarity and aggregation state of drug. The dispersion showed no evidence of precipitation of drug for 48 h, and resisted destabilization due to freeze-thaw cycles or centrifugation. The dispersed phase globules measured a mean size of 84 nm and uv-spectrophotometric studies indicated the presence of self-aggregated amphotericin B. The present formulation showed a 92% decrease in haemolysis of human RBC in vitro when compared with the commercially available Fungizone. The LD(50) in mice was estimated to be 3.4 mg/kg. The results indicate that the formulation holds promise for development as a safer and efficacious alternative for amphotericin B therapy.

[Short-term prognosis of the course of acute coronary syndrome (according to analysis of data of one-channel ECG in phase space and variability of the heart rhythm)].

74 patients with different variants of coronary syndrome have been observed at myocardial infarction department of #5 Kiev sity clinical hospital. Investigations showed that 66 (89%) patients from 74 had their symmetry dynamics of T wave in phase space correlated with a clinical picture and outcome of the treatment carried out in the cardioresuscitation of patients with acute coronary syndrome (ACS). Patients with positive results of the treatment of ACS had their T-waves decreased, patients who had not improved had their T-waves stable on increased. These changes were statistically certain. Changes of symmetry of T-wave in a phase space have a good correlation with treatment results.