Search

Brain metastasis (BrM) is an area of unmet medical need that poses unique therapeutic challenges and heralds a dismal prognosis. The intracranial tumor microenvironment (TME) presents several challenges, including the therapy-resistant blood–brain barrier, a unique immune milieu, distinct intercellular interactions, and specific metabolic conditions, that are responsible for treatment failures and poor clinical outcomes. There is a complex interplay between malignant cells that metastasize to the central nervous system (CNS) and the native TME. Cancer cells take advantage of vascular, neuronal, immune, and anatomical vulnerabilities to proliferate with mechanisms specific to the CNS. In this review, we discuss unique aspects of the TME in the context of brain metastases and pathways through which the TME may hold the key to the discovery of new and effective therapies for patients with BrM.

Introduction: Ocular burns are ophthalmic emergencies due to their visual morbidity. The extent of ocular surface involvement at the time of presentation is critically associated with visual outcome. Comprehensive ocular examination and prompt management is needed to optimize visual outcome. Objective: This study aims to evaluate the epidemiological trends, clinical features of patients with ocular burns and to determine their relationship with visual outcome. Methods:This prospective, cross-sectional study was conducted on 96 consecutive in-patients who were admitted in the Department of Plastic surgery and Burns in our hospital and sought opinion for ocular burns, irrespective of age and sex. The main outcome measures evaluated were clinical features of ocular burns and prognostic factors associated with visual impairment. Results: In our study, the mean age (S.D.) of patients was 32.83+/- 18.70 years with both males and females equally affected. The most common mode of injury was thermal injury due to domestic accidents (88.5%). 74% of patients had bilateral ocular presentation. Lid burns (42.2%) and lid edema (41.1%) were the most common ocular findings. About 5.2% of eyes showed corneal involvement. About 14 eyes (7.3%) had severe ocular complications among which one eye developed phthisis bulbi. 20 eyes (16.1%) had visual acuity of less than 6/60 causing visual morbidity. In multivariate logistic regression analysis, corneal involvement (p

No abstract available. Article truncated after 150 words. History of Present Illness: A 55-year-old man with a past medical history significant for endocarditis secondary to intravenous drug use, osteomyelitis of the right lower extremity was admitted for ankle debridement. Pre-operative assessment revealed no acute illness complaints and no significant findings on physical examination except for the ongoing right lower extremity wound. He did well during the approximate one-hour “incision and drainage of the right lower extremity wound”, but became severely hypotensive just after the removal of the tourniquet placed on his right lower extremity. Soon thereafter he experienced pulseless electrical activity (PEA) cardiac arrest and was intubated with return of spontaneous circulation being achieved rapidly after the addition of vasopressors. He remained intubated and on pressors when transferred to the intensive care unit for further management. PMH, PSH, SH, and FH: • S/P Right lower extremity incision and drainage for suspected osteomyelitis as above • Distant history of endocarditis related …

Mucormycosis, formerly known as zygomycosis, is a potentially fatal invasive fungal disease (IFD) caused by fungi in the Mucorales order and the zygomycetes class. Mucormycosis is a rare but deadly fungal infection that generally affects those who have weakened immune systems. The infection has the potential to spread throughout the body. Death is a possibility with this type of severe infection. It’s important to get treatment. If left untreated, mucormycosis can be fatal. Zygomycosis has a high mortality of 70–100%. The prevalence of mucormycosis in India is approximately 80 times that of developed countries, with 0.14 cases per 1000 population. The main aim and purpose of this review related to overview and history, causative agents, epidemiology, etiopathogenesis, transmission, types, clinical features, recent advances in diagnosis and treatment of Mucormycosis. A systematic literature search was conducted in the electronic databases of PubMed, Google Scholar and relevant sources. It will be helpful for those who work in the medicine field to explore their knowledge about mucormycosis.

Herbal plants are the most valuable resources to prevent from many illness and to treat the many disorders in humans. Cissus quadrangularis is a one of the traditional medicine and belonging to vitaceae family. In Ayurvedha medicinal system this plant is used to treat many diseases like diabetes, snake bites, rheumatic pain, cardiovascular diseases. Cissus quadrangularis used as anticancer properties against MG63 human osteocarcinoma cells. Stem of the Cissus quadrangularis is an edible vegetable and the plant commonly called as ‘bone setter’. Our present study was analyzed the primary phyto constituents present the different solvents of Cissus quadrangularis and antioxidant activity. Three different extracts aqueous, methanol and ethanol were used to find out the phytoconstituents and antioxidant properties. The results were reveals that the plant Cissus quadrangularis consists of numerous primary and secondary phytoconstituents. Flavonoids and tannins were found to be higher in ethanol extracts, legnings, saponins was high in methanol extracts. Antioxidant study also reveals ethanol extracts shows more antioxidant activity than other two solvents.

BACKGROUND AND PURPOSE: Asymmetries in the circle of Willis have been associated with several conditions, including migraines and stroke, but they may also be age-dependent. This study examined the impact of age and age-dependent changes in cerebral perfusion on circle of Willis anatomy in healthy children and adults. MATERIALS AND METHODS: We performed an observational, cross-sectional study of bright and black-blood imaging of the proximal cerebral vasculature using TOF-MRA and T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (T2-SPACE) imaging at the level of the circle of Willis in 23 healthy children and 43 healthy adults (4–74 years of age). We compared arterial diameters measured manually and cerebral perfusion via pseudocontinuous arterial spin-labeling between children and adults. RESULTS: We found that the summed cross-sectional area of the circle of Willis is larger in children than in adults, though the effect size was smaller with T2-SPACE-based measurements than with TOF-MRA. The circle of Willis is also more symmetric in children, and nonvisualized segments occur more frequently in adults than in children. Moreover, the size and symmetry of the circle of Willis correlate with cerebral perfusion. CONCLUSIONS: Our results demonstrate that the circle of Willis is different in size and symmetry in healthy children compared with adults, likely associated with developmental changes in cerebral perfusion. Further work is needed to understand why asymmetric vasculature develops in some but not all adults.

BACKGROUND: Mucormycosis is a rapidly progressing, life threatening, opportunistic fungal infection caused by angioinvasive mucorales species of the phylum zygomycetes.The major risk factors of the disease are uncontrolled diabetes mellitus, COVID-19 infection,prolonged usage of high dose of systemic corticosteroids,immunocompromised status and neutropenia. These create a nidus for fungal infection through nasal mucosa which spreads up through paranasal sinuses into orbit manifesting as rhino-orbital mucormycosis. AIM 1. To study the epidemiology and various clinical patterns of presentation of rhino-orbital mucormycosis in post covid patients. 2. To analyse the risk factors associated with progression of rhino-orbital mucormycosis in post covid patients. METHODS: A retrospective study of 25 patients diagnosed as rhino-orbital mucormycosis in post covid patients at Government Kilpauk Medical College Hospital between April and July 2021 was done. RESULTS: In our study,males (64%) are more commonly affected with age preponderance of 51-60 years(28%). The mean age of presentation was 52.1+/-4.49years.The most common symptom of the disease is nasal discharge with sinus and orbital pain(52%).The most common form of presentation is orbital apex syndrome in seven patients(28%).Five patients had loss of vision, of which four were due to central retinal artery occlusion(16%) and one due to cavernous sinus thrombosis.MRI imaging of these patients showed sinus involvement(100%) in all cases ,orbital(48%) and cerebral involvement(8%).The major risk factors responsible for progression of disease in our study are uncontrolled diabetes, prolonged usage of high dose steroid therapy, medial wall involvement, optic nerve head involvement and artery thrombosis. CONCLUSION: Post covid patients presenting with nasal discharge with sinus and orbital pain symptoms need to be diagnosed and managed properly to avoid spread of infection and fatal complications. Aggressive surgical debridement of infected tissues helps in increasing the survival rate of the patients. Patients with risk factors need to be closely monitored to prevent vision loss and cosmetic disfigurement surgeries.

In chronic infections and in cancer, persistent antigen stimulation under suboptimal conditions can lead to the induction of T-cell exhaustion. Exhausted T cells are characterized by an increased expression of inhibitory markers and a progressive and hierarchical loss of function. Although cancer-induced exhaustion in CD8 T cells has been well-characterized and identified as a therapeutic target (i.e., via checkpoint inhibition), in-depth analyses of exhaustion in other immune cell types, including CD4 T cells, is wanting. While perhaps attributable to the contextual discovery of exhaustion amidst chronic viral infection, the lack of thorough inquiry into CD4 T-cell exhaustion is particularly surprising given their important role in orchestrating immune responses through T-helper and direct cytotoxic functions. Current work suggests that CD4 T-cell exhaustion may indeed be prevalent, and as CD4 T cells have been implicated in various disease pathologies, such exhaustion is likely to be clinically relevant. Defining phenotypic exhaustion in the various CD4 T-cell subsets and how it influences immune responses and disease severity will be crucial to understanding collective immune dysfunction in a variety of pathologies. In this review, we will discuss mechanistic and clinical evidence for CD4 T-cell exhaustion in cancer. Further insight into the derivation and manifestation of exhaustive processes in CD4 T cells could reveal novel therapeutic targets to abrogate CD4 T-cell exhaustion in cancer and induce a robust antitumor immune response.

The Severe Acute Respiratory Syndrome (SARS) coronavirus-2 is a novel coronavirus belonging to the family Coronaviridae originating in Wuhan, China has created a impact across the globe. The disease has been declared a pandemic by the WHO on March 11, 2020. In this review, an update on virology, pathophysiology, clinical presentation with detailed update on oral manifestations .

The present research shows an adsorbent prepared from an agricultural waste was studied for its efficiency in removal color. The process parameters were analyzed like agitation time, initial dye concentration, adsorbent dose, pH and temperature. The experimental data analysed by the Langmuir and Freundlich models of adsorption. The adsorption isotherm data were fitted well to Langmuir isotherm. The Kinetic data obtained at different concentrations were analysed using a pseudo first order and second order kinetic model. The experimental data fitted very well the pseudo second-order kinetic model. This study proves that the novel activated carbon is a promising adsorbent for remediation of textile effluent in a sustainable manner.

Purpose: To study the prevalence of dry eye in a hospital-based population and to study the tear film parameters in dry eye patients presenting with symptoms of grittiness and foreign body sensation attending the ophthalmology outpatient department of Karpaga Vinayaka Institute of Medical Sciences, Chengalpattu, Tamil Nadu. Materials and Methods: Cross Sectional study conducted in the out patient department of our department among patients presenting with symptoms suggestive of dry eyes both male and female patients consenting to the study were included. Results: A total of 125 participants were enrolled, of these 38 had dry eye, 67 had long duration of work. 86 patients had complaints suggestive of dry eye. 38 had all 3 parameters tested abnormal. Tear film was evaluated with Schirmer test, TBUT, TMH and a proforma to record patient demographic details, symptoms, test values and dry eye diagnosis. Conclusion: our study showed 86 participants with symptoms such as grittiness, foreign body sensation, dryness, burning sensation and 38 patients had dry eye and required treatment such as lubricants. Poor quality and function of tears, combined with subnormal ocular surface, makes patients symptomatic and on evaluation show ocular surface disease dry eye which can be treated accordingly to relieve the patient of symptoms and improve the quality of life. Thus routine and early examination of tear function and ocular surface parameters should form a part of the workup of all patients with symptoms of dry eye. Keywords: Dry eye, Grittiness, Schirmer test, TMH, TBUT.

Purpose: Danvatirsen is a therapeutic antisense oligonucleotide (ASO) that selectively targets STAT3 and has shown clinical activity in two phase I clinical studies. We interrogated the clinical mechanism of action using danvatirsen-treated patient samples and conducted back-translational studies to further elucidate its immunomodulatory mechanism of action. Experimental Design: Paired biopsies and blood samples from danvatirsen-treated patients were evaluated using immunohistochemistry and gene-expression analysis. To gain mechanistic insight, we used mass cytometry, flow cytometry, and immunofluorescence analysis of CT26 tumors treated with a mouse surrogate STAT3 ASO, and human immune cells were treated in vitro with danvatirsen. Results: Within the tumors of treated patients, danvatirsen uptake was observed mainly in cells of the tumor microenvironment (TME). Gene expression analysis comparing baseline and on-treatment tumor samples showed increased expression of proinflammatory genes. In mouse models, STAT3 ASO demonstrated partial tumor growth inhibition and enhanced the antitumor activity when combined with anti–PD-L1. Immune profiling revealed reduced STAT3 protein in immune and stromal cells, and decreased suppressive cytokines correlating with increased proinflammatory macrophages and cytokine production. These changes led to enhanced T-cell abundance and function in combination with anti–PD-L1. Conclusions: STAT3 ASO treatment reverses a suppressive TME and promotes proinflammatory gene expression changes in patients' tumors and mouse models. Preclinical data provide evidence that ASO-mediated inhibition of STAT3 in the immune compartment is sufficient to remodel the TME and enhance the activity of checkpoint blockade without direct STAT3 inhibition in tumor cells. Collectively, these data provide a rationale for testing this combination in the clinic.

We report the clinical and microbiological features of contact lens-related mixed infectious keratitis caused by a spore-forming filamentous fungus and a rare gram-negative bacterial infection. A 66-year-old Caucasian female presented with right eye (OD) pain after sleeping in her 2-weekly contact lenses for 3 days. On presentation, corrected distance visual acuity was 0.46 LogMAR OD and 0.20 in the left eye. Slit lamp biomicroscopy revealed a 1.9 mm by 1.9 mm area of dense stromal infiltrate with epithelial defect. Corneal scrapes grew Aspergillus fumigatus and Pseudomonas koreensis, and culture-directed microbial therapy with oral and topical voriconazole and topical fortified gentamicin along with regular debridement resulted in slow resolution of the infection, leaving a dense stromal scar in the visual axis requiring penetrating keratoplasty. Mixed infectious keratitis caused by filamentous fungi and gram-negative bacteria is rare. Pseudomonas koreensis infection has not been previously reported as a cause of infectious keratitis in humans. In our experience, these mixed infections require prolonged systemic and topical therapy and the secondary scarring may require surgical intervention for vision rehabilitation.

Split cord malformation (SCM) is a developmental disorder that is usually symptomatic and diagnosed in childhood. The majority of these lesions are in the thoracic and lumbar spine, with only 1%-3% of cases found in the cervical spine. This is a case report of a 55-year-old female patient with an unremarkable medical history who presented with neck pain. Upon workup, she was found to have extensive developmental anomalies throughout her cervical and thoracic spine, including an incidentally found type 2 SCM and multiple autofused vertebrae. There are only 6 similar studies published in the literature. There was extensive facet degeneration in her cervical spine, which was suspected to be the etiology of her neck pain. This case illustrates the rare finding of asymptomatic adult cervical SCM and the likely significance of her autofused vertebrae causing accelerated symptomatic facet spondylosis.

The coronavirus disease 2019 (COVID-19) is highly infectious, with the current pandemic causing significant morbidity and mortality worldwide. As large numbers of frontline healthcare workers (HCWs) have also been infected and several have died, there is much global concern about protective measures for them, particularly those performing surgery or other procedures with close patient contact. Since the beginning of the pandemic, there has been and there remains a shortage in the supply of personal protective equipment (PPE), including the N95 filtering facepiece (FFP) respirator, for HCWs. N95 respirators have filtration efficiency of 95% of aerosol particles. Surgical N95 respirators are used where fluid resistance is also required together with respiratory protection, e.g. during surgery or interventional procedures. The shortage of N95 respirators may be overcome by extended use and reuse - comprising rotation and decontamination by approved techniques. The additional role of powered air-purifying respirators (PAPR) is also discussed.

AIM: To estimate the proportion of incidence of glaucoma cases in a screening camp conducted at a tertiary Ophthalmology centre. BACKGROUND: 1,2 Glaucoma is the second leading cause of blindness in the adult population in India .The diagnosis of glaucoma was based on the presence of at least two of the following criteria:IOP ≥ 21 mmHg,glaucomatous optic disc abnormalities,and glaucomatous visual field defects. MATERIALS AND METHODS: A prospective, cross sectional study was conducted on 100 consecutive individuals aged more than 40 years who came to our hospital Ophthalmology department from 08-March, 2020 to 14-March, 2020. All subjects underwent a comprehensive eye examination including brief history taking, slit lamp examination, applanation tonometry, gonioscopy, pachymetry, dilated fundus examination using slit lamp biomicroscopy with 90D lens and automated perimetry. RESULTS: One hundred individuals including 43 males and 57 females are screened.The screening result found to be positive in 9 (9%) subjects who underwent further diagnostic evaluation which concluded 3 cases of Normotension glaucoma,5 cases of Primary angle closure glaucoma and 1 individual with Secondary Glaucoma. CONCLUSION: Periodical glaucoma screening helps to detect more number of glaucoma cases thereby preventing blindness. Routine glaucoma screening for individuals more than 40 years should be strictly followed by Ophthalmologists in the society

Introduction: The optimal treatment paradigm for brain metastasis that recurs locally after initial radiosurgery (BMRS) remains an area of active investigation. Here, we report outcomes for patients with BMRS treated with stereotactic laser ablation (SLA, also known as laser interstitial thermal therapy, LITT)followed by consolidation radiosurgery (cSRS). Methods: Clinical outcome of 20 patients with 21histologically confirmed BMRS treated with SLA followed by consolidation SRS and >6 months follow-up were collected retrospectively across three participating institutions. Results: Consolidation SRS (5 Gy x 5 or 6 Gy x 5) wascarried out 16-73 days (median of 26 days) post-SLA of BMRS. There were no new neurological deficits after SLA/cSRS. While 3/21 (14.3%) patients suffered temporary Karnofsky Performance Score (KPS) decline after SLA, no KPS declines was observed after cSRS. There were no 30-day mortalities or wound complications. Two patients required re-admission within 30 days of cSRS (severe headache that resolved with steroid therapy (n=1) and new onset seizure (n=1)). With a median follow-up of 228 days (range: 178-1367 days), the local control rate at 6 and 12 months (LC6, LC12) was 100%. All showed diminished FLAIR volume surrounding the SLA/cSRS treated BMRS at the six-month follow-up; none of the patients required steroid for symptoms attributable to these BMRS. These results compare favorably to the available literature for repeat SRS or SLA-only treatment of BMRS.Conclusions: This multi-institutional experience supports further investigations of SLA/cSRS as a treatment strategyfor BMRS.

The 24 h and 14-day relationship between indoor and outdoor PM2.5, PM10, NO2, relative humidity, and temperature were assessed for an elementary school (site 1), a laboratory (site 2), and a residential unit (site 3) in Gainesville city, Florida. The primary aim of this study was to introduce a biplot-based PCA approach to visualize and validate the correlation among indoor and outdoor air quality data. The Spearman coefficients showed a stronger correlation among these target environmental measurements on site 1 and site 2, while it showed a weaker correlation on site 3. The biplot-based PCA regression performed higher dependency for site 1 and site 2 (p &lt, 0.001) when compared to the correlation values and showed a lower dependency for site 3. The results displayed a mismatch between the biplot-based PCA and correlation analysis for site 3. The method utilized in this paper can be implemented in studies and analyzes high volumes of multiple building environmental measurements along with optimized visualization.

Pure and dual doped ZnO nanoparticles were synthesized via the wet chemical method. The synthesized samples were characterized by XRD, HR-SEM/EDS, HR-TEM, UV–Vis, PL, FT-IR, and FT-Raman spectral measurements. The prepared ZnO nanoparticles exhibit a hexagonal wurtzite structure and [Ce–La, La–Gd, Gd–Ce] rare earth dual doped ZnO nanoparticles was confirmed from the shift in XRD peaks position, cell parameter and also changes in the peaks intensity. HR-SEM/EDS and HR-TEM show spherical in shape with less agglomeration on the surface of all samples and the images are clearly revealed that the particle size ~ 40 nm (PZ), 14 nm (ZCL3), 16 nm (ZLG3) and 28 nm (ZGC3). UV–Vis spectra show a strong Ultraviolet region absorbance for ZCL3 sample with the low Energy band gap value of 2.81 eV. The presences of the functional group and molecular vibrations are characterized by employing the FT-IR and FT-Raman spectra. From the PL spectra, it was found that the peak position of all samples produces a visible emission. The photocatalytic performance of the synthesized doped nanoparticles found to exhibit better degradation of MB dye under solar irradiation ZCL3 showed an increase in the photo catalytic decolorization efficiency. The bactericidal activity of dual doped ZnO nanoparticles was investigated against Gram-positive and Gram-negative bacteria and compare with standard ampicillin. We observe that ZCL3 sample have excellent antibacterial activity against Gram-negative bacteria (P. mirabilis) and the mean zone of inhibition ~ 20 mm.

Aims To investigate the safety and cost-effectiveness of interscalene brachial plexus block/regional anaesthesia (ISB-RA) in patients undergoing reverse total shoulder replacement. Patients and methods This retrospective study included 15 patients with symptomatic rotator cuff arthropathy who underwent reverse total shoulder arthroplasty (rTSA) under ISB-RA without general anaesthesia in the beach chair position from 2010 to 2018. The mean patient age was 77 years (range 59-82 years). Patients had associated medical comorbidities: American Society of Anesthesiologists (ASA) grade 2-4. Assessed parameters were: duration of anaesthesia, intra-operative systolic blood pressure variation, sedation and vasopressor use, duration of post-operative recovery, recovery scores, length of stay, and complications. A robust cost analysis was also performed. Results The mean (range) duration of anaesthesia was 38.66 (20-60) min. Maximum and minimum intra-operative systolic blood pressure ranges were 130-210 and 75-145 mmHg, respectively (mean [range] drop, 74.13 [33-125] mmHg). Mean (range) propofol dose was 1.74 (1-3.0) mg/kg/h. The Median (interquartile range) post-operative recovery time was 30 (20-50) min. The mean (range) postoperative recovery score (local scale, range 5-28 where lower values are superior) was 5.2 (5-8). The mean (range) length of stay was 8 (1-20 days); the two included patients with ASA grade 2 were both discharged within 24 hours. One patient with predisposing history developed pneumonia; however, there were no complications related to ISB-RA. The mean (range) cost per patient was £101.36 (£59.80-£132.20). Conclusions Our data demonstrate that rTSA under ISB-RA is safe, comfortable, and cost-effective. Notably, patients with ASA grade 2 who underwent rTSA under ISB-RA had a reduced length of stay and were discharged within 24 hours. Clinical relevance rTSA under ISB-RA is potentially a safe, cost-effective, and viable alternative for patients with multiple comorbidities.

Minimally invasive lumbar laminectomies utilize tubular retractors to minimize tissue disturbance, blood loss, and hospital length of stay compared to open operations. Here, we highlight the operative treatment of a 68-yr-old male entailing a 2-level minimally invasive lumbar laminectomy and foraminotomy at L2-L3 and L3-L4. The patient initially presented with symptoms of treatment-refractory lower extremity numbness and limited ambulation. His imaging demonstrated coronal scoliosis and severe lumbar central and foraminal stenosis at L2-L3 and L3-L4, with enlarged spinous processes, laminae, and facets. The patient consented to the procedure and publication of their image. The operation proceeded with the patient in a prone position with paramedian dissection to the lamina through a minimally invasive tubular retractor. Laminectomies and foraminotomies were performed at each level with high-speed drill and a Kerrison rongeur, with care to identify and protect the relevant spinal nerve roots. Postoperatively, the patient reported significantly reduced numbness and improved ambulation, with a well-healed surgical incision notably smaller than those produced in an open operation.

White Blood Cell (WBC) cancer or leukemia is one of the serious cancers that threaten the existence of human beings. In spite of its prevalence and serious consequences, it is mostly diagnosed through manual practices. The risks of inappropriate, sub-standard and wrong or biased diagnosis are high in manual methods. So, there is a need exists for automatic diagnosis and classification method that can replace the manual process. Leukemia is mainly classified into acute and chronic types. The current research work proposed a computer-based application to classify the disease. In the feature extraction stage, we use excellent physical properties to improve the diagnostic system’s accuracy, based on Enhanced Color Co-Occurrence Matrix. The study is aimed at identification and classification of chronic lymphocytic leukemia using microscopic images of WBCs based on Enhanced Virtual Neural Network (EVNN) classification. The proposed method achieved optimum accuracy in detection and classification of leukemia from WBC images. Thus, the study results establish the superiority of the proposed method in automated diagnosis of leukemia. The values achieved by the proposed method in terms of sensitivity, specificity, accuracy, and error rate were 97.8%, 89.9%, 76.6%, and 2.2%, respectively. Furthermore, the system could predict the disease in prior through images, and the probabilities of disease detection are also highly optimistic.

INTRODUCTION Radiation necrosis (RN) occurs in 9–14% of patients after stereotactic radiosurgery (SRS) for brain metastases (BM). Medical management (MM) with steroids is a common first-line therapy, with variable response and numerous side effects, especially regarding immunotherapy. Laser interstitial thermal therapy (LITT) has been introduced as an efficacious, steroid-reducing alternative, however limited data exists comparing LITT to MM. METHODS Patients with biopsy-proven RN after SRS for BM who received LITT or MM at two academic centers were retrospectively reviewed. Treatment failure was defined as radiographic progression that necessitated a change in management. Measurements of total (TLV) and contrast-enhancing lesion volume (ceLV) were obtained from MRI by semi-automated analysis using the BrainLab iPlan Cranial 3.0 software. RESULTS Eighty-one patients were followed for 11.7 (4.3–27.0) months and 57 (70%) received LITT. Steroid cessation occurred at a median of 37 days post-LITT compared to 162 days after MM (p< 0.01). Treatment failure occurred in 5% of LITT patients at 4.0 (3.2–4.8) months and 13% of MM patients at 4.4 (4.1–5.3) months (p >0.05). Patients were 3.2 times more likely to be weaned off steroids when treated with LITT compared to MM (p< 0.01), when controlled for age, pre-operative ceLV, and post-operative seizure on multivariate analysis. Both groups demonstrated decreasing TLV and ceLV between baseline and last follow-up MRI. At 6–9 months, the LITT cohort demonstrated a -59% change in ceLV compared to -7% with MM (p >0.05). The LITT cohort demonstrated a significant decrease in ceLV between scans at 0–2 and 6–9 months (p< 0.01). The MM group did not demonstrate a statistically significant decrease in ceLV until 12 months. CONCLUSION This study suggests that LITT for RN significantly reduces the time to steroid cessation, and earlier radiographic response to treatment by LITT. Large, prospective trials are needed to validate these findings.

Diabetic foot and lower limb complications are one of serious diabetes related complaints that in most cases lead to infections and amputations. While the Mean Foot Temperature (MFT) of a healthy human being is $30.6 \pm 2.6 ^{\circ}\mathrm{C}$ [1], any underlying pathology may cause an unusual variation in the temperature distribution as a result of inflammatory response of the human body. The quantitative and qualitative characterization of the temperature distributions in plantar feet helps in detecting the differences between healthy and at-risk foot. Contrasting the plantar foot into 4 angiosomes, the dissimilarity matrix could be an approach to ascertain the similarity and dissimilarity between the contralateral and ipsilateral angiosomes. Thus making it a suitable measure for quantitative analysis of angiosome temperature patterns which can thereby expedite the detection of ‘at-risk’ regions of plantar foot.

Nowadays many of the conventional materials are effectively replaced by composite materials, because of their light weight to stiffness ratio. Gears are the very essential components in mechanical power transmission, and drive in the most industrial rotating machinery. Polymer gears are used in motion and power transmission under different loads and speeds. Gears are generally made from metallic materials but recently advanced polymeric materials were developed because of low cost, light weight, high strength and improved performance of the system. Nylon, polymers, acetal and derlin are the structural polymeric materials used in printing and robotics, mechanical machines such as washing machines, sugarcane crushing machine and gear pump that are used for power and speed transmission. The paper investigates the polymer matrix composites gear with different fiber proportions. The main objective is to make glass fiber reinforced polymer gears using epoxy resin with various proportions of E-glass CSM (5%, 10%, 15%, 20%). The work investigates the wear testing of polymer gears of different proportions with metal gear using gear testing rig. The paper focused on morphology of fractured surfaces of polymer gears using scanning electron microscope. Finally, the gear is modeled in Catia software and imported to Ansys for static structural application.

Cognitive decline is common among patients with low- and high-grade glioma and can significantly impact quality of life. Although cognitive outcomes have been studied after therapeutic interventions such as surgery and radiation, it is important to understand the impact of the disease process itself prior to any interventions. Neurocognitive domains of interest in this disease context include intellectual function and premorbid ability, executive function, learning and memory, attention, language function, processing speed, visuospatial function, motor function, and emotional function. Here, we review oncologic factors associated with more neurocognitive impairment, key neurocognitive tasks relevant to glioma patient assessment, as well as the relevance of the human neural connectome in understanding cognitive dysfunction in glioma patients. A contextual understanding of glioma-functional network disruption and its impact on cognition is critical in the surgical management of eloquent area tumors.

The rise of immunotherapy (IT) in oncological treatment has greatly improved outcomes in a number of disease states. However, its use in tumors of the central nervous system (CNS) remains limited for multiple reasons related to the unique immunologic tumor microenvironment. As such, it is valuable to consider the intersection of IT with additional treatment methods that may improve access to the CNS and effectiveness of existing IT modalities. One such combination is the pairing of IT with localized hyperthermia (HT) generated through technologies such as laser interstitial thermal therapy (LITT). The wide-ranging immunomodulatory effects of localized and whole-body HT have been investigated for some time. Hyperthermia has demonstrated immunostimulatory effects at the level of tumor cells, immune cells, and the broader environment governing potential immune surveillance. A thorough understanding of these effects as well as the current and upcoming investigations of such in combination with IT is important in considering the future directions of neuro-oncology.

Paget's “seed and soil” hypothesis of metastatic spread has acted as a foundation of the field for over a century, with continued evolution as mechanisms of the process have been elucidated. The central nervous system (CNS) presents a unique soil through this lens, relatively isolated from peripheral circulation and immune surveillance with distinct cellular and structural composition. Research in primary and metastatic brain tumors has demonstrated that this tumor microenvironment (TME) plays an essential role in the growth of CNS tumors. In each case, the cancerous cells develop complex and bidirectional relationships that reorganize the local TME and reprogram the CNS cells, including endothelial cells, pericytes, astrocytes, microglia, infiltrating monocytes, and lymphocytes. These interactions create a structurally and immunologically permissive TME with malignant processes promoting positive feedback loops and systemic consequences. Strategies to interrupt interactions with the native CNS components, on “salting the soil,” to create an inhospitable environment are promising in the preclinical setting. This review aims to examine the general and specific pathways thus far investigated in brain metastases and related work in glioma to identify targetable mechanisms that may have general application across the spectrum of intracranial tumors.

Skin cancer is a highly contagious disease that spreads over the human body very rapidly within a short period of time. Skin cancer and rashes may seem to be similar to each other in the eyes of a dermatologist so it is not easy to determine whether the skin is affected by rashes or skin cancer. Rashes are generic terms used by people and doctors to denote the changes in the skin such as skin infections, skin allergies, skin diseases. Dermatologist identifies skin cancer from rashes when skin does not heal over medication for a prolonged period of time and continues to spread rapidly to other parts of the skin meanwhile knowing the differences between rashes and skin cancer can help a person seek the necessary help or avoid anxiety about a noncancerous rash. The objective of the paper is to differentiate skin cancer from rashes and helps in detecting skin cancer in human skin. Pervious researches were successful in classifying the skin cancer types using image classification and this modal detects and differentiates skin cancer images from rashes images by using CNN[Convolutional neural network] and classify the images as skin cancer or rashes. The model is able to classify the image as skin cancer affected image or rashes image and obtained an average accuracy of 80.2% for 20 epochs.

Recent studies have described the remarkable clinical outcome of anti-CD19 chimeric antigen receptor (CAR) T cells in treating B-cell malignancies. However, over 50% of patients develop life-threatening toxicities associated with cytokine release syndrome which may limit its utilization in low-resource settings. To mitigate the toxicity, we designed a novel humanized anti-CD19 CAR T cells by humanizing the framework region of single-chain variable fragment (scFv) derived from a murine FMC63 mAb and combining it with CD8α transmembrane domain, 4-1BB costimulatory domain, and CD3ζ signaling domain (h1CAR19-8BBζ). Docking studies followed by molecular dynamics simulation revealed that the humanized anti-CD19 scFv (h1CAR19) establishes higher binding affinity and has a flexible molecular structure with CD19 antigen compared with murine scFv (mCAR19). Ex vivo studies with CAR T cells generated from healthy donors and patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) expressing either h1CAR19 or mCAR19 showed comparable antitumor activity and proliferation. More importantly, h1CAR19-8BBζ T cells produced lower levels of cytokines (IFNγ, TNFα) upon antigen encounter and reduced the induction of IL6 cytokine from monocytes than mCAR19-8BBζ T cells. There was a comparable proliferation of h1CAR19-8BBζ T cells and mCAR19-8BBζ T cells upon repeated antigen encounter. Finally, h1CAR19-8BBζ T cells efficiently eliminated NALM6 tumor cells in a preclinical model. In conclusion, the distinct structural modification in CAR design confers the novel humanized anti-CD19 CAR with a favorable balance of efficacy to toxicity providing a rationale to test this construct in a phase I trial.

The cerebellum was long perceived to be a region of limited importance with primary functions in the regulation of motor control. A degree of its functional topography in motor modulation has been traditionally appreciated. However, an evolving body of evidence supports its role in a range of cognitive processes, including executive decision making, language, emotional processing, and working memory. To this end, numerous studies of cerebellar stroke syndromes as well as investigations with functional magnetic resonance imaging and diffusion tensor imaging have given clinicians a better model of the functional topography within the cerebellum and the essential lanes of communication with the cerebrum. With this deeper understanding, neurosurgeons should integrate these domains into the perioperative evaluation and postoperative rehabilitation of patients with cerebellar tumors. This review aims to discuss these understandings and identify valuable tools for implementation into clinical practice.

IL-9 is produced by Th9 cells and is classically known as a growth-promoting cytokine. Although protumorigenic functions of IL-9 are described in T cell lymphoma, recently, we and others have reported anti-tumor activities of IL-9 in melanoma mediated by mast cells and CD8+ T cells. However, involvement of IL-9 in invasive breast and cervical cancer remains unexplored. In this study, we demonstrate IL-9–dependent inhibition of metastasis of both human breast (MDA-MB-231 and MCF-7) and cervical (HeLa) tumor cells in physiological three-dimensional invasion assays. To dissect underlying mechanisms of IL-9–mediated suppression of invasion, we analyzed IL-9–dependent pathways of cancer cell metastasis, including proteolysis, contractility, and focal adhesion dynamics. IL-9 markedly blocked tumor cell–collagen degradation, highlighting the effects of IL-9 on extracellular matrix remodeling. Moreover, IL-9 significantly reduced phosphorylation of myosin L chain and resultant actomyosin contractility and also increased focal adhesion formation. Finally, IL-9 suppressed IL-17– and IFN-γ–induced metastasis of both human breast (MDA-MB-231) and cervical (HeLa) cancer cells. In conclusion, IL-9 inhibits the metastatic potential of breast and cervical cancer cells by controlling extracellular matrix remodeling and cellular contractility.

Interstitial lung disease with nephrotic syndrome and junctional epidermolysis bullosa is caused by biallelic mutations in the integrin gene ITGA3 and is associated with death in infancy. We describe a variant of this syndrome with delayed presentation of symptoms and prolonged survival.

Adolescence and early adulthood are periods of major biological, economic and social transitions for rural youth. They provide a critical window of opportunity for addressing chronic nutritional deficits from childhood, for “catch-up” growth, for providing a solid foundation for a healthy productive and reproductive life, and for arresting the intergenerational transmission of malnutrition. In this study we show that rural transformation processes are associated with improvements in rural youth nutrition – malnutrition and underweight – in nearly all regions, although the pace of change varies considerably across countries. Most low- and middle-income countries (LMICs) are faced with the double burden of malnutrition and overweight/obesity, and in some countries this double burden is increasing, with the prevalence of underweight and overweight/obesity rising concurrently. The effect of rural transformation processes on rural youth nutrition is mediated by its effects on the external and personal domains of the “food environment”. Transformation of agri-food systems are bringing about large changes in the diets of rural youth in LMICs, and particularly of the younger age groups, who appear to be witnessing rapid dietary transitions. The Young Lives dataset suggest that certain near-universal changes in patterns of dietary and nutrient intake patterns can be discerned in LMICs, although the pace of change varies. Dietary transitions are also driven by “globalisation influences” – especially dissemination of information through digital/social media and food industry advertising and marketing strategies – even in countries with low/slow rural transformation. Our results show that rural transformation processes can have both positive and negative effects on rural youth nutrition in LMICs. Despite the globalisation influences of international trade and agri-food systems, dietary changes in individual LMICs are still influenced by national policies and production patterns. Understanding the pathways to impact of rural transformation on rural youth nutrition is crucial for designing “nutrition-sensitive” rural transformation policies.

INTRODUCTION Laser interstitial thermal therapy (LITT) is a minimally-invasive treatment option for radiographically-progressive (RP) brain metastases. This study compares the functional outcomes of LITT vs resection (RS) for lesions in or near the primary motor cortex (PMC). METHODS Retrospective review was performed of patients treated for PMC lesions by LITT or RS. Functional outcomes were graded relative to pre-treatment symptoms and categorized as improved, stable, or worsened at 30, 90, and 180 days post-LITT/RS. RESULTS 36 patients were identified with median follow-up of 194 days (IQR 72-503), age 64 years (57-72), and estimated baseline KPS 80 (80-90). 35 (98%) had pre-treatment weakness or motor seizure; 15 (42%) received LITT and 21 (58%) RS; all RS were performed with intra-operative motor mapping while LITT were not. All LITT patients were treated for RP lesions (radiation necrosis (RN) or disease progression) vs. 24% of RS patients (p< 0.01). LITT patients trended towards smaller lesions (1.9 cm vs 2.7 cm, p=0.03) and were more likely to show RN (67% vs 5%, p< 0.01) and be discharged home (87% vs 52%, p=0.04), with shorter ICU (0 vs 1 day, p< 0.01) and hospital stays (1 vs. 2 days, p< 0.01). At 30 days, 89% of surviving patients who received RS had stable or improved symptoms, compared to 46% of the LITT cohort (p=0.02). At 90 days, the difference was 88% to 50% (p=0.07), and at 180 days 100% to 80% (p=0.2941). CONCLUSIONS In the short term (30 days), patients with PMC lesions have better functional outcomes when treated with RS compared to LITT, while those who survive to the 180-day timepoint experience similar outcomes. These differences are likely due to transient, expected post-LITT edema that subsides with time. Taken together, prognosis and patient priorities are important considerations in the decision between LITT and RS.

INTRODUCTION Laser interstitial thermal therapy (LITT) is an effective minimally-invasive treatment option for intracranial tumors. Our group produced plasmonics-active gold nanostars (GNS) designed to preferentially accumulate within intracranial tumors and amplify the ablative capacity of LITT while better conforming to tumor boundaries and protecting surrounding tissue. MATERIALS AND METHODS The 12nm GNS were synthesized using reduced HAuCl4 with Na3C6H5O7 seeds, mixed with AgNO3, C6H8O6, and HAuCL4, and coated with polyethylene glycol then functionalized with methoxy PEG thiol. CT-2A glioma cells were intracranially implanted into mice, followed 18 days later by IV injection of GNS. PET-CT was performed at 10-minutes, 24-, and 72-hours post-GNS administration, with autoradiography (AR) and histopathology (HP) on sacrifice after the last scan. To test the impact of GNS on LITT coverage capacity in appropriately sized ex vivo models, we utilized agarose gel-based phantoms incorporating control and GNS-infused central “tumors” in multiple shapes. LITT was administered with the NeuroBlate System. RESULTS In vivo, GNS preferentially accumulated within intracranial tumors on PET-CT at the 24- and 72-hour timepoints. AR and HP confirmed high GNS accumulation within tumor. Ex vivo, in cuboid tumor phantoms, the GNS-infused phantom heated 5.5x faster than the control, rising 0.49°C per minute compared to 0.09°C. In a split-cylinder tumor phantom with half containing GNS, the GNS-infused border heated 2x faster and the surrounding area was exposed to 30% lower temperatures. In a GNS-infused star-shaped phantom, the heat spread contoured along phantom boundaries. CONCLUSIONS Our results provide evidence for use of GNS to improve the specificity, efficiency, and potentially safety of LITT. The in vivo data support selective accumulation within intracranial tumors, and the GNS-infused phantom experiments demonstrate increased rates of heating within the tumor model, heat contouring to tumor borders, and decreased heating of surrounding regions representing normal structures.

INTRODUCTION Stereotactic radiosurgery (SRS) is a highly effective therapy for newly diagnosed brain metastases. Risk factors for new-onset seizures after SRS have not been well established. In this study, we aimed to characterize the variables predictive of seizure risk. METHODS Patients treated with SRS for newly diagnosed brain metastases were retrospectively reviewed at a single institution. Data on baseline demographics, radiation parameters, and clinical courses were collected. RESULTS 120 patients without previous seizure history were identified. Median age was 65 years (56-70.8) and baseline KPS 90 (80-90). 16 (13%) patients developed new-onset seizures within 3 months of SRS. In analyses comparing patients with and without new-onset seizures, there was no association between new-onset seizures and baseline KPS(90:80, p=0.48), prior resection (31%:28%, p=0.76), prior WBRT (6%:10%, p=1), immunotherapy or chemotherapy within 1 month (31%:21%, p=0.52 and 56%:57%, p=1), primary tumor site (p=0.07), number of lesions (2.2:3, p=0.21), cerebellar (25%:37%, p=0.41) or brainstem involvement (19%:14%, p=0.71), irradiated maximum target diameter (2.8:2.0cm p=0.191), maximum target volume (7.6:2.9 cm3 p=0.133), total dose of radiation (25:20Gy, p = 0.12), or use of fractionation (56%:35%, p=0.11). However, there was a significant difference in the total irradiated target volume (11.6 vs. 3.8 cm3, p=0.019) and a trend toward increased post-treatment seizures among patients with a total irradiated volume greater than 10cm3 (20%:9%, p=0.11, OR 2.4 [0.85-6.4]). Patients with seizures were also more likely to have received steroids (69%:34%, p=0.012) and AEDs (28%:15%, p=0.021) prior to SRS. CONCLUSIONS Our data suggest that total treatment volume is associated with new-onset seizures within 3 months of SRS. The association between seizures and exposure to steroids or AEDs prior to SRS may be a surrogate for neurologic symptoms at presentation. Patients undergoing SRS to larger volumes and necessitating prophylactic steroids or AEDs may benefit from counseling or intensification of anti-seizure therapy.

No abstract available. Article truncated after 150 words. A 35-year-old lady with a history of depression and anxiety presented to the emergency room with worsening shortness of breath after receiving polymethylmethacrylate (PMMA) injections in her buttock for cosmetic purposes in Mexico. Immediately after the injection in the outpatient office, she became acutely short of breath, tachypneic, and tachycardic. She was brought to the emergency room where she was hypoxic with oxygen saturations in the low 80s on a non-rebreather, tachypneic with a respiratory rate in the 40s, and tachycardic with heart rates in 140s. She was emergently intubated. A CTA of the chest demonstrated bilateral ground glass opacities throughout, most pronounced in the upper lobes which progressed to significant bilateral airspace disease consistent with acute respiratory distress syndrome (Figure 1). Her neurological examination declined over the course of her hospitalization. An MRI of the brain with contrast demonstrated bilateral foci of susceptibility artifact throughout the entirety of the …

Introduction Laser interstitial thermal therapy (LITT) is a minimally-invasive treatment option for radiographically-progressive (RP) brain metastases. This study compares the functional outcomes of LITT vs resection (RS) for lesions in or near the primary motor cortex (PMC). Methods Retrospective review was performed of patients treated for PMC lesions by LITT or RS. Functional outcomes were graded relative to pre-treatment symptoms and categorized as improved, stable, or worsened at 30, 90, and 180 days post-LITT/RS. Results 36 patients were identified with median follow-up of 194 days (IQR 72–503), age 64 years (57–72), and estimated baseline KPS 80 (80–90). 35 (98%) had pre-treatment weakness or motor seizure; 15 (42%) received LITT and 21 (58%) RS; all RS were performed with intra-operative motor mapping while LITT were not. All LITT patients were treated for RP lesions (radiation necrosis (RN) or disease progression) vs. 24% of RS patients (p Conclusion In the short term (30 days), patients with PMC lesions have better functional outcomes when treated with RS compared to LITT, while those who survive to the 180-day timepoint experience similar outcomes. These differences are likely due to transient, expected post-LITT edema that subsides with time. Taken together, prognosis and patient priorities are important considerations in the decision between LITT and RS.