Preparation of Microsponge Drug Delivery System (MSDDS) Followed by a Scale-Up Approach.

In 1987, Won invented the solid-phase porous microsphere (MS), which stores bioactive compounds in many interconnected voids. Spherical particles (5-300 µm), MS, may form clusters of smaller spheres, resulting in many benefits. The current investigation focussed on gel-encased formulation, which can be suitable for dermal usage. First, quasi-emulsion (w/o/w) solvent evaporation was used to prepare 5-fluorouracil (5 FU) MS particles. The final product was characterized (SEM shows porous structure, FTIR and DSC showed drug compatibility with excipients, and gel formulation is shear-thinning) and further scaled up using the 8-fold method. Furthermore, CCD (Central Composite Design) was implemented to obtain the optimized results. After optimizing the conditions, including the polymer (600 mg, ethyl cellulose (EC), eudragit RS 100 (ERS)), stirring speed (1197 rpm), and surfactant concentration (2% w/v), we achieved the following results: optimal yield (63%), mean particle size (152 µm), drug entrapment efficiency (76%), and cumulative drug release (74.24% within 8 h). These findings are promising for industrial applications and align with the objectives outlined in UN Sustainable Development Goals 3, 9, and 17, as well as the goals of the G20 initiative.

How does deep learning/machine learning perform in comparison to radiologists in distinguishing glioblastomas (or grade IV astrocytomas) from primary CNS lymphomas?: a meta-analysis and systematic review.

BACKGROUND: Several studies have been published comparing deep learning (DL)/machine learning (ML) to radiologists in differentiating PCNSLs from GBMs with equivocal results. We aimed to perform this meta-analysis to evaluate the diagnostic accuracy of ML/DL versus radiologists in classifying PCNSL versus GBM using MRI. METHODOLOGY: The study was performed in accordance with PRISMA guidelines. Data was extracted and interpreted by two researchers with 12 and 23 years' experience, respectively, and QUADAS-2 tool was used for quality and risk-bias assessment. We constructed contingency tables to derive sensitivity, specificity accuracy, summary receiver operating characteristic (SROC) curve, and the area under the curve (AUC). RESULTS: Our search identified 11 studies, of which 8 satisfied our inclusion criteria and restricted the analysis in each study to reporting the model showing highest accuracy, with a total sample size of 1159 patients. The random effects model showed a pooled sensitivity of 0.89 [95% CI:0.84-0.92] for ML and 0.82 [95% CI:0.76-0.87] for radiologists. Pooled specificity was 0.88 [95% CI: 0.84-0.91] for ML and 0.90 [95% CI: 0.81-0.95] for radiologists. Pooled accuracy was 0.88 [95% CI: 0.86-0.90] for ML and 0.86 [95% CI: 0.78-0.91] for radiologists. Pooled AUC of ML was 0.94 [95% CI:0.92-0.96]and for radiologists, it was 0.90 [95% CI: 0.84-0.93]. CONCLUSIONS: MRI-based ML/DL techniques can complement radiologists to improve the accuracy of classifying GBMs from PCNSL, possibly reduce the need for a biopsy, and avoid any unwanted neurosurgical resection of a PCNSL.

Declining Use of Corticosteroids for Crohn's Disease Has Implications for Study Recruitment: Results of a Pilot Randomized Controlled Trial.

BACKGROUND: Corticosteroids (CS) have been used extensively to induce remission in Crohn's disease (CD); however, they are associated with severe side effects. We hypothesized that the administration of an exclusive enteral nutrition (EEN) formula to CS would lead to increased CD remission rates and to decreased CS-related adverse events. We proposed to undertake a pilot study comparing EEN and CS therapy to CS alone to assess decrease symptoms and inflammatory markers over 6 weeks. AIM: The overall aim was to assess study feasibility based on recruitment rates and acceptability of treatment in arms involving EEN. METHODS: The pilot study intended to recruit 100 adult patients with active CD who had been prescribed CS to induce remission as part of their care. The patients were randomized to one of three arms: (i) standard-dose CS; (ii) standard-dose CS plus EEN (Modulen 1.5 kcal); or (iii) short-course CS plus EEN. RESULTS: A total of 2009 CD patients attending gastroenterology clinics were screened from October 2018 to November 2019. Prednisone was prescribed to only 6.8% (27/399) of patients with active CD attending outpatient clinics. Of the remaining 372 patients with active CD, 34.8% (139/399) started or escalated immunosuppressant or biologics, 49.6% (198/399) underwent further investigation and 8.8% (35/399) were offered an alternative treatment (e.g., antibiotics, surgery or investigational agents in clinical trials). Only three patients were enrolled in the study (recruitment rate 11%; 3/27), and the study was terminated for poor recruitment. CONCLUSION: The apparent decline in use of CS for treatment of CD has implications for CS use as an entry criterion for clinical trials.

Stimulus modality influences session-to-session transfer of training effects in auditory and tactile streaming-based P300 brain-computer interfaces.

Despite recent successes, patients suffering from locked-in syndrome (LIS) still struggle to communicate using vision-independent brain-computer interfaces (BCIs). In this study, we compared auditory and tactile BCIs, regarding training effects and cross-stimulus-modality transfer effects, when switching between stimulus modalities. We utilized a streaming-based P300 BCI, which was developed as a low workload approach to prevent potential BCI-inefficiency. We randomly assigned 20 healthy participants to two groups. The participants received three sessions of training either using an auditory BCI or using a tactile BCI. In an additional fourth session, BCI versions were switched to explore possible cross-stimulus-modality transfer effects. Both BCI versions could be operated successfully in the first session by the majority of the participants, with the tactile BCI being experienced as more intuitive. Significant training effects were found mostly in the auditory BCI group and strong evidence for a cross-stimulus-modality transfer occurred for the auditory training group that switched to the tactile version but not vice versa. All participants were able to control at least one BCI version, suggesting that the investigated paradigms are generally feasible and merit further research into their applicability with LIS end-users. Individual preferences regarding stimulus modality should be considered.

Practical consensus recommendations regarding role of mastectomy in metastatic breast cancer.

Whether to recommend mastectomy in metastatic disease or not has been a matter of debate. Is local therapy, such as mastectomy, of any benefit in advanced breast cancer is the main question. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations for the benefit of community oncologists.

Socio-demographic and Clinical Characteristics of Patients who Attempt Suicide: A Hospital-based Study from Eastern India.

INTRODUCTION: Suicide has become an important public health concern with a high number of deaths and increasing number of attempted suicides every year. There are multiple factors that underlie a suicide attempt. Although mental illness and severe stress have long been known to be associated with suicide, socio-demographic and clinical characteristics of those attempting suicide can also provide indications of suicidal intent. The present study aimed to explore the socio-demographic and clinical characteristics of patients in Kolkata, India who attempted suicide. METHODS: Consecutive patients (n = 100) with failed suicide attempt who were referred to the psychiatry department of 2 multispecialty hospitals in Kolkata were included in the study. Their socio-demographic details and clinical characteristics were recorded. Suicidal intent and depressive symptoms were assessed and psychosocial risk factors were identified following detailed clinical interview. RESULTS: Suicide attempt was more frequent among younger female patients. Reaction to stress was the most common risk factor. The majority of attempts were impulsive in nature rather than planned. CONCLUSION: Young adults under stress are more vulnerable. Early identification of such individuals and psychosocial support to prevent suicidal ideation is vital.

Tension pneumoperitoneum: a very rare complication of acute gangrenous appendicitis.

Tension pneumoperitoneum is a very rare consequence of acute gangrenous appendicitis. We report a case of a 32-year-old woman who presented with abdominal pain, progressively increasing abdominal distension, profound hemodynamic instability and ventilatory compromise. The diagnosis of tension pneumoperitoneum was confirmed by computed tomography, which showed compression of the intra-abdominal viscera and liver (saddlebag sign) by a large volume of intraperitoneal free air. Urgent needle decompression was done as an emergency measure. Exploratory laparotomy, planned due to persistent peritonitis, revealed gangrenous appendicitis with perforation near its base. Appendicectomy with excision of gangrenous portion of caecum was performed. The purpose of the reporting this case is to highlight that the tension pneumoperitoneum can be, very rarely, associated with gangrenous appendicitis and timely diagnosis is very important for the emergency management of this deadly condition.

Neuroprotective impact of prothymosin alpha-derived hexapeptide against retinal ischemia-reperfusion.

Prothymosin alpha (ProTα) has robustness roles against brain and retinal ischemia or serum-starvation stress. In the ProTα sequence, the active core 30-amino acid peptide/P30 (a.a.49-78) is necessary for the original neuroprotective actions against ischemia. Moreover, the 9-amino acid peptide sequence/P9 (a.a.52-60) in P30 still shows neuroprotective activity against brain and retinal ischemia, though P9 is less potent than P30. As the previous structure-activity relationship study for ProTα may not be enough, the possibility still exists that any sequence smaller than P9 retains potent neuroprotective activity. When different P9- and P30-related peptides were intravitreally injected 24h after retinal ischemia in mice, the 6-amino acid peptide/P6 (NEVDEE, a.a.51-56) showed potent protective effects against ischemia-induced retinal functional deficits, which are equipotent to the level of P30 peptide in electroretinography (ERG) and histological damage in Hematoxylin and Eosin (HE) staining. Further studies using ERG and HE staining suggested that intravitreal or intravenous (i.v.) injection with modified P6 peptide/P6Q (NEVDQE) potently inhibited retinal ischemia-induced functional and histological damage. In an immunohistochemical analysis, the ischemia-induced loss of retinal ganglion, bipolar, amacrine and photoreceptor cells were inhibited by a systemic administration with P6Q peptide 24h after the ischemic stress. In addition, systemic post-treatment with P6Q peptide significantly inhibited retinal ischemia-induced microglia and astrocyte activation in terms of increased ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) intensity, respectively, as well as their morphological changes, increased number and migration. Thus, this study demonstrates the therapeutic significance of modified P6 peptide P6Q (NEVDQE) derived from 6-amino acid peptide (P6) in ProTα against ischemic damage.

Effects of training and motivation on auditory P300 brain-computer interface performance.

OBJECTIVES: Brain-computer interface (BCI) technology aims at helping end-users with severe motor paralysis to communicate with their environment without using the natural output pathways of the brain. For end-users in complete paralysis, loss of gaze control may necessitate non-visual BCI systems. The present study investigated the effect of training on performance with an auditory P300 multi-class speller paradigm. For half of the participants, spatial cues were added to the auditory stimuli to see whether performance can be further optimized. The influence of motivation, mood and workload on performance and P300 component was also examined. METHODS: In five sessions, 16 healthy participants were instructed to spell several words by attending to animal sounds representing the rows and columns of a 5 × 5 letter matrix. RESULTS: 81% of the participants achieved an average online accuracy of ⩾ 70%. From the first to the fifth session information transfer rates increased from 3.72 bits/min to 5.63 bits/min. Motivation significantly influenced P300 amplitude and online ITR. No significant facilitative effect of spatial cues on performance was observed. CONCLUSIONS: Training improves performance in an auditory BCI paradigm. Motivation influences performance and P300 amplitude. SIGNIFICANCE: The described auditory BCI system may help end-users to communicate independently of gaze control with their environment.

Training leads to increased auditory brain-computer interface performance of end-users with motor impairments.

OBJECTIVE: Auditory brain-computer interfaces are an assistive technology that can restore communication for motor impaired end-users. Such non-visual brain-computer interface paradigms are of particular importance for end-users that may lose or have lost gaze control. We attempted to show that motor impaired end-users can learn to control an auditory speller on the basis of event-related potentials. METHODS: Five end-users with motor impairments, two of whom with additional visual impairments, participated in five sessions. We applied a newly developed auditory brain-computer interface paradigm with natural sounds and directional cues. RESULTS: Three of five end-users learned to select symbols using this method. Averaged over all five end-users the information transfer rate increased by more than 1800% from the first session (0.17 bits/min) to the last session (3.08 bits/min). The two best end-users achieved information transfer rates of 5.78 bits/min and accuracies of 92%. CONCLUSIONS: Our results show that an auditory BCI with a combination of natural sounds and directional cues, can be controlled by end-users with motor impairment. Training improves the performance of end-users to the level of healthy controls. SIGNIFICANCE: To our knowledge, this is the first time end-users with motor impairments controlled an auditory brain-computer interface speller with such high accuracy and information transfer rates. Further, our results demonstrate that operating a BCI with event-related potentials benefits from training and specifically end-users may require more than one session to develop their full potential.

Non-enteric infections, antibiotic use, and risk of development of functional gastrointestinal disorders.

BACKGROUND: Gastrointestinal infections are risk factors for irritable bowel syndrome (IBS) and functional dyspepsia (FD). We investigated whether non-enteric infections and antibiotic exposure are also associated with the development of functional gastrointestinal disorders (FGIDs). METHODS: In a nested case-control study, random samples of Olmsted County, MN, were mailed valid self-report questionnaires from 1988 through 1994, and then follow-up questionnaires from 1995 through 2003. Survey responders who did not report any FGID symptoms at baseline, but then reported such symptoms in at least one subsequent survey, were classified as new-onset cases. Age-matched controls were individuals who did not have symptoms at either the initial or subsequent surveys. KEY RESULTS: The overall response rate was 78% to the initial survey and 52% to the follow-up survey. Based on the responses, 316 participants had a new onset of an FGID (43 IBS constipation, 95 IBS diarrhea, 25 IBS mixed, and 153 other FGIDs, including FD) and 250 did not (controls). Around 76% (241/316) of cases reported a non-enteric infection vs 66% (166/250) of the controls. The frequency of enteric infections was similar between the two groups. Of the new FGID cases, 83% had a non-enteric infection that was treated with antibiotic. In a logistic regression model, treatment with antibiotics for a non-gastrointestinal infection was associated with the development of an FGID (odds ratio = 1.90; 95% CI: 1.21-2.98; p = 0.005), after adjusting for age and sex. CONCLUSIONS & INFERENCES: Based on a case-control study, treatment of a non-gastrointestinal infection with antibiotics appears to be a risk factor for development of an FGID.

Epidemiological Aspect and common Bacterial and Fungal isolates from Suppurative Corneal Ulcer in Mymensingh Region.

This prospective study was done to find out the epidemiological factors of suppurative corneal ulcer and the common causative bacterial and fungal isolates from the, patients with suppurative corneal ulcer in secondary and tertiary level hospital at Mymensingh region. A total 100 samples of corneal scrapings were collected purposively from clinically diagnosed suppurative corneal ulcer patients from March 18, 2012 to March 17, 2013. Out of the total 100 samples, bacterial species were 29(29%) cases and the fungal spacies were 71(71%) identified by the culture in blood agar, chocolate agar and sabouraud's agar media and also by microscopic examination. The bacterial species were streptococcus pneumonae 12 cases (12%), Staphylococcus aureus 9 cases (9%), pseudomonas in 6 cases (6%), and Streptococcus pyoganes 2 cases (2%). Fungal species were aspergillus fumigatus 61 cases (61%), aspergillus niger 10 cases (10%). Out of the study populations, most of the populations were from the age group of 41 to 60 years (39 %), followed 21 to 40 years (34%) age group. Considering the sex, male were 67%, female were 33%. The majority of patients came from the rural area of Mymensingh region; occupationally they were farmers (44%). Ocular trauma due to agricultural materials was the most common associated factor (71%). The etiological and epidemiological pattern of suppurative corneal ulcer varies significantly with geographical region, patient population and health of the cornea. The present study was carried out to explore the epidemiological pattern, causative bacterial and fungal specie by laboratory procedure from corneal scraping and to invent a prospective guide line for the management of corneal ulcer in the community.

Comparative anti-proliferative activity of some new 2-(arylazo)phenolate-palladium (II) complexes and cisplatin against some human cancer cell lines.

In this study, we report the synthesis of four 2-(arylazo)phenol-Pd(II) complexes and their anti-proliferative property against the human lung cancer (A549), cervical cancer (HeLa), and ovarian teratocarcinoma (PA-1) cell lines with cisplatin as the gold standard. One of the complexes, [Pd(L(2))2], induced robust apoptosis in all the chosen cells, as revealed by annexin-V-positive/propidium iodide dual staining, increased sub-G1 cell cycle population, and significant morphological changes in the treated cells. The Pd complex inflicted mitochondrial dysfunction leading to mitochondrial membrane potential loss, reactive oxygen species generation and release of cytosolic cytochrome c that activated caspase-9 and caspase-3 proteins which finally caused programmed cell death.

Bulk growth of ninhydrin single crystals by solvent evaporation method and its characterization for SHG and THG applications.

Ninhydrin is a well-known compound generally used in amino acid synthesis and also for detecting the latent fingerprints on porous surfaces. Single crystals can be grown by dissolving the compound in double distilled water at ambient temperature, and can be used as a potential material for second and third harmonic generation applications. The grown specimen was subjected to different characterization techniques in order to find out its suitability for device fabrication. Its lattice dimensions have been confirmed by X-ray powder diffraction and its crystalline quality has been assessed by high resolution X-ray diffraction and X-ray topography methods. The presence of functional groups was identified from HETCOR analysis and confirmed the absence of impurities during crystallization. Its optical properties have been examined by photoluminescence and birefringence analyses. Its thermal parameters such as thermal diffusivity, thermal conductivity and specific capacity have been carried out by following photopyroelectric method. Third order nonlinear optical measurements have been carried out using Z-scan technique and its nonlinear optical absorption coefficient has been determined.