Stimulation of Biological Structures on the Nanoscale Using Interfaces with Large Built-In Spontaneous Polarizations.

The electric potential stimulation of biological structures in aqueous environments is well-known to be a result of the gating of voltage-gated ion channels. Such voltage-gated ion channels are ubiquitous in the membranes of a wide variety of cells and they play central roles in a wide variety of sensing mechanisms and neuronal functions in biological systems. Experimental studies of ion-channel gating are frequently conducted using path-clamp techniques by placing a cumbersome external electrode in the vicinity of the extracellular side of the ion channel. Recently, it has been demonstrated that laser-induced polarization of nanoscale quantum dots can produce voltage sufficient to gate voltage-gated ion channels. This study specifically focuses on a new method of gating voltage-gated ion channels using 2D structures made of materials exhibiting large naturally occurring spontaneous polarizations, thereby eliminating the need for an external electrode or an illuminating laser. The work presents the use of self-polarizing semiconductor flakes, namely, 2H-SiC, ZnO, and GaN, to produce electric potential that is sufficient to gate voltage-gated ion channels when existing in proximity to it.

Capacity building for pediatric neuro-oncology in Pakistan- a project by my child matters program of Foundation S.

Introduction: Initiated in June 2019, this collaborative effort involved 15 public and private sector hospitals in Pakistan. The primary objective was to enhance the capacity for pediatric neuro-oncology (PNO) care, supported by a My Child Matters/Foundation S grant. Methods: We aimed to establish and operate Multidisciplinary Tumor Boards (MTBs) on a national scale, covering 76% of the population (185.7 million people). In response to the COVID-19 pandemic, MTBs transitioned to videoconferencing. Fifteen hospitals with essential infrastructure participated, holding monthly sessions addressing diagnostic and treatment challenges. Patient cases were anonymized for confidentiality. Educational initiatives, originally planned as in-person events, shifted to a virtual format, enabling continued implementation and collaboration despite pandemic constraints. Results: A total of 124 meetings were conducted, addressing 545 cases. To augment knowledge, awareness, and expertise, over 40 longitudinal lectures were organized for healthcare professionals engaged in PNO care. Additionally, two symposia with international collaborators and keynote speakers were also held to raise national awareness. The project achieved significant milestones, including the development of standardized national treatment protocols for low-grade glioma, medulloblastoma, and high-grade glioma. Further protocols are currently under development. Notably, Pakistan's first pediatric neuro-oncology fellowship program was launched, producing two graduates and increasing the number of trained pediatric neuro-oncologists in the country to three. Discussion: The initiative exemplifies the potential for capacity building in PNO within low-middle income countries. Success is attributed to intra-national twinning programs, emphasizing collaborative efforts. Efforts are underway to establish a national case registry for PNO, ensuring a comprehensive and organized approach to monitoring and managing cases. This collaborative initiative, supported by the My Child Matters/Foundation S grant, showcases the success of capacity building in pediatric neuro-oncology in low-middle income countries. The establishment of treatment protocols, fellowship programs, and regional tumor boards highlights the potential for sustainable improvements in PNO care.

The Use of Semiconductor Quantum Dots with Large, Built-In Spontaneous Polarizations for the Electric Potential Stimulation of Biological Structures on the Nanoscale.

The feasibility of using quantum dots fabricated from materials with built-in spontaneous polarizations for the electric potential stimulation of biological structures in aqueous environments is evaluated by modeling the electric potential produced in the vicinity of such quantum dots. By modeling the external potential created by the spherical nanoscale region of a material with spontaneous polarization, and by considering Debye screening in the vicinity of the quantum dot, it is found that electric potential around these nanostructures is sufficient to cause physiological effects in selected biological systems. These findings suggest that quantum dots may be used in lieu of quantum dots with polarizations produced using an external laser to cause physiological effects. The elimination of the external laser represents a significant benefit of using quantum dots with permanent, built-in spontaneous polarization.

Impact of dedicated pediatric neuro-oncological services in a developing country: A single-institution, Pakistani experience.

INTRODUCTION: Brain tumors are the most common solid neoplasms and the second most common malignancy in the pediatric age group. Due to the complexity of their management, pediatric central nervous system (CNS) tumors are not a priority in low- and middle-income countries (LMICs). METHODS: In an attempt to improve the survival rate and overall care, we introduced a dedicated pediatric neuro-oncology service in our institute and evaluated its impact by dividing the pre- and post-era into two cohorts and comparing them: 1998-2013 (16 years: cohort A) and 2014-2019 (6 years: cohort B, after the start of dedicated neuro-oncology services). RESULTS: We observed that after the implementation of a proper neuro-oncology service, the proportion of patients treated with curative intent increased, and survival improved in cohort B. The patient volume also increased from 15.5 per year in cohort A to 44.8 per year in cohort B. The percentage of children given radiation therapy also increased significantly, while the proportion of children treated with chemotherapy remained stable. CONCLUSION: A dedicated multidisciplinary team trained and knowledgeable in the specialty of pediatric neuro-oncology can enhance and improve outcomes, and supportive care and help can provide good quality of life to children and their families with brain neoplasms.

Building the ecosystem for pediatric neuro-oncology care in Pakistan: Results of a 7-year long twinning program between Canada and Pakistan.

BACKGROUND: Low- and middle-income countries sustain the majority of pediatric cancer burden, with significantly poorer survival rates compared to high-income countries. Collaboration between institutions in low- and middle-income countries and high-income countries is one of the ways to improve cancer outcomes. METHODS: Patient characteristics and effects of a pediatric neuro-oncology twinning program between the Hospital for Sick Children in Toronto, Canada and several hospitals in Karachi, Pakistan over 7 years are described in this article. RESULTS: A total of 460 patients were included in the study. The most common primary central nervous system tumors were low-grade gliomas (26.7%), followed by medulloblastomas (18%), high-grade gliomas (15%), ependymomas (11%), and craniopharyngiomas (11.7%). Changes to the proposed management plans were made in consultation with expert physicians from the Hospital for Sick Children in Toronto, Canada. On average, 24% of the discussed cases required a change in the original management plan over the course of the twinning program. However, a decreasing trend in change in management plans was observed, from 36% during the first 3.5 years to 16% in the last 3 years. This program also led to the launch of a national pediatric neuro-oncology telemedicine program in Pakistan. CONCLUSIONS: Multidisciplinary and collaborative efforts by experts from across the world have aided in the correct diagnosis and treatment of children with brain tumors and helped establish local treatment protocols. This experience may be a model for other low- and middle-income countries that are planning on creating similar programs.

Correlation of clinical and radiological predictors of retinoblastoma with high-risk histopathological features.

INTRODUCTION: Retinoblastoma (RB) tumors having high-risk histopathologic features (HRFs) have an increased risk of metastasis and disease relapse. However, RB has not been studied widely in Pakistan. Therefore, we evaluated the association of clinical, histopathologic, and radiological findings with HRFs in patients with RB who were treated at the Indus Health & Hospital Network in Karachi, Pakistan. METHODS: We enrolled treatment-naïve patients with RB who received upfront enucleation from September 2017 to February 2021. We evaluated enucleated eyes with the Intraocular Classification of Retinoblastoma system and classified HRFs as invasion of the anterior chamber, including the iris and ciliary body, or massive invasion of the choroid, sclera, or optic nerve (postlaminar and/or up to the transection line). RESULTS: Of 117 patients with RB treated at our institution during the study period, 54 received upfront enucleation. Unilateral disease was present in 92.6% of cases. The most frequent disease signs and symptoms included the presence of vitreous seeds (30.6%) and leukocoria (100%), respectively. The most frequent HRFs and radiological findings comprised massive choroidal invasion (15.1%) and anterior chamber enhancement (66.7%), respectively. The majority (62.9%) of patients did not exhibit any HRFs. Female sex, pseudohypopyon, iris neovascularization, buphthalmos, and glaucoma had significant predictive ability for HRF occurrence. CONCLUSION: Pseudohypopyon, iris neovascularization, buphthalmos, and glaucoma are important clinical factors that should be taken into consideration before the management of RB. Early recognition of high-risk histopathological and radiological features is essential for appropriate treatment of RB.

Chemotherapy induced histopathological changes in retinoblastoma, assessment of high risk predictive factors & its correlation with comorbid conditions.

Background & Objectives: Retinoblastoma is a malignant intraocular tumor and its treatment requires a multidisciplinary approach. Chemotherapy is an important modality in treatment of retinoblastoma. The purpose of this study was to assess the histopathological changes in retinoblastomas treated with chemotherapy along with correlation of comorbid conditions with high risk histopathological factors (HRF). Methods: All post-chemotherapy enucleated eye specimens received in the pathology department between 2017 to 2021 were included in the study. Slides were retrieved and reviewed for chemotherapeutic effects, tumor regression, and for assessment of HRF. Patient demographic data, information regarding chemotherapy and co-morbid conditions were retrieved through the hospital database. Chi-square was used to analyze the relation between comorbid conditions and HRF. Results: Chemotherapeutic effects were seen in all eyes with varying degrees of responses. Necrosis, calcification, and gliosis were the most common findings. The majority of eyes showed tumor occupying less than 50% of the eye whereas complete regression was noted in one eye only. Retinal detachment, glaucoma, and buphthalmos were the most common comorbid conditions at the time of diagnosis. Patients with glaucoma were more likely to have ciliary body invasion. Kaplan Meier analysis showed that patients with more than two HRF had decreased survival rates in comparison to those with one or no HRF. Conclusion: Histopathological evaluation of chemotherapy-treated eyes shows varying degrees of response to chemotherapy. Post enucleation histopathological evaluation of the globe plays an important role in assessing disease activity and guiding further treatment to prevent metastasis.

Retinoblastoma Presentation and Survival: A four-year analysis from a tertiary care hospital.

OBJECTIVE: To study the clinical presentation, treatment, and outcome of Retinoblastoma (Rb) in a tertiary care hospital of Pakistan. METHODS: A retrospective study was conducted in the Department of Pediatric Hematology Oncology, The Indus Hospital (TIH), Karachi from 1st June 2013 to 30th June 2017. Data including patients' demography, clinical symptoms and duration, laterality, extent of the tumor, type of treatment, relapse, and final outcome were extracted and evaluated with respect to progression and survival. RESULTS: A total of 93 patients were included; 34.4% were boys. The median age at presentation was 30 months. Leukocoria was the commonest symptom (61.3%), followed by proptosis (37.6%). Unilateral disease was seen in 59.1%, extraocular tumors in 43.5% and metastasis in 28.1%. Enucleation was performed on 46.2%, chemotherapy given to 80.6% and external beam radiation therapy to 29.3% patients. CONCLUSION: Delayed presentation, recurrent disease, extraocular disease and metastasis on presentation were factors affecting outcome in our cohort. Awareness about the early warning signs and symptoms in both public and health professionals for early recognition and timely management are mandatory to decrease morbidity and mortality.

Outcomes of Group D Retinoblastoma With Resistant Vitreous Seeds After Integration of Intravitreal Chemotherapy to the Treatment Protocol.

INTRODUCTION: A major therapeutic challenge in the salvage of Group D retinoblastoma eyes is the poor response of vitreous seeds to intravenous chemotherapy. The novel use of intravitreal melphalan has greatly impacted the salvage of such eyes; however, concerns regarding its safety and toxicity still exist, particularly in dark-eyed children. This study aims to evaluate our experience and determine the visual and anatomical outcomes of intravitreal melphalan in group D retinoblastoma with resistant vitreous seeds. METHOD: All patients, from August 2018 to February 2020, with group D retinoblastoma harboring vitreous seeds refractory to first-line chemo reduction regimen with vincristine, etoposide, and carboplatin for six cycles plus local consolidation with thermotherapy or cryotherapy were evaluated. Fifteen eyes of 15 patients that fulfilled the eligibility criteria and received intravitreal melphalan were retrospectively reviewed for demographics, iris color, treatments offered, seed inactivation, globe survival, visual acuity, and complications. RESULT: Mean age at presentation was 22 months for bilateral disease and 36 months for unilateral disease. A total of 77 injections were administered (mean, five injections per eye) with doses ranging from 20 µg to 30 µg. Complete seed control was seen in 13 of 15 (87%) eyes, and globe salvage was possible in 11 of 15 (73%) eyes. Eyes with macular tumor had visual acuity ranging from 6/36 (0.8) to 6/60 (1.0). SIx of eight eyes (75%) with extra macular tumors had vision 0.4 or better. CONCLUSION: Intravitreal melphalan seems like a promising treatment modality in group D retinoblastoma with resistant vitreous seeds having dark eyes. Amblyopia therapy may play an important role in attaining maximal visual benefits in these children.

Advancing Methods of Assessing Bone Quality to Expand Screening for Osteoporosis.

CONTEXT: Dual-energy x-ray absorptiometry (DXA) limits osteoporosis screening because of machine size, technical requirements for operation, and exposure to ionizing radiation. OBJECTIVE: To establish data ranges from calcaneus ultrasonography (US) that correspond to bone mineral density (BMD) stratification identified by DXA and to determine whether vitamin D concentration adds to US bone health assessment. METHODS: Patients scheduled for DXA at the Robert C. Byrd Clinic, a rural primary care facility in Lewisburg, West Virginia, were recruited from June 2015 to June 2016. Ultrasonography was used to scan the left and right calcaneus of the patients, and blood was collected from a finger prick for vitamin D analysis. Information was collected regarding Fracture Risk Assessment tool parameters, menstrual history, and drug and supplement use. The correlations within and between DXA and US measurements were calculated, as well as the correlations between DXA and US measurements and vitamin D levels. Predictive performance of US readings on bone health determined by DXA scan was assessed with area under the curve analysis using receiver operator characteristic curves. RESULTS: Ninety-nine participants were included. Ultrasonography readings of either the left or right foot were predictive of good vs poor bone quality. No differences were found between US scans of the left foot vs the right foot. Area under the curve values for US BMD T scores for the left and right foot were 0.69 and 0.68, respectively. There was no correlation between DXA- and US-assessed BMD and vitamin D concentrations. Negative correlations were observed between the DXA BMD T scores and vitamin D concentration of the spine and right hip; negative correlations were also observed in the Z score from the spine in the subset of participants who reported not taking vitamin D supplements. CONCLUSION: Ultrasonography of the calcaneus offers a low-cost, efficient means to screen bone health. The affordability and mobility of a US machine enables its use as a screening method that may be applicable to large numbers of people. This study established a T score greater than -1.05 as an indicator of good bone quality and a T score less than -1.05 as an indicator of poor bone quality when using US for BMD screening.

Community adaptations to an impending food desert in rural Appalachia, USA.

INTRODUCTION: The United States Department of Agriculture (USDA) describes a food desert as an urban neighborhood or rural town without ready access to fresh, healthy, and affordable food. An estimated 2.3 million rural Americans live in food deserts. One goal of the USDA is to eliminate food deserts. However, at a time when some food deserts are being eliminated, hundreds of grocery stores are closing, causing other food deserts to arise. The literature is scarce on how a community adapts to an impending food desert. Alderson, West Virginia, USA (population 1184) rallied to face an impending food desert when the only grocery store in town closed in December 2014. This study investigated how this small rural community adapted to its oncoming food desert. METHODS: A community member survey was administered to 155 Alderson families (49%) to determine how the new food desert affected family food acquisition and storage behaviors. A restaurant survey was given to the town's four restaurants to determine how the food desert affected their businesses. Sales data for a new food hub (Green Grocer) was obtained to see if this new initiative offset the negative effects of the food desert. ANOVA and t-tests were used to compare group numerical data. Two group response rates were compared by testing the equality of two proportions. Categorical data were analyzed with the χ2 or frequency distribution analysis. Group averages are reported as mean ± standard error of the mean. Significance for all analyses was set at p<0.05. RESULTS: Even though 86% of the population shopped at the new Green Grocer, 77% did most of their shopping at a store at least 17.7 km (11 miles) from home. The number of long-distance monthly shopping trips made after the food desert (3.3±0.4) did not change significantly (p=0.16) from the number before the food desert (2.8±0.3). Price comparisons among the Green Grocer and three distant supermarkets showed a 30% savings by traveling to distant supermarkets. Frequency of monthly restaurant visits did not change after the emergence of the food desert (2.98±0.54 vs 3.05±0.51, p=0.85). However, restaurant patrons requested to buy fresh produce and dairy from the restaurants to use for their own home cooking. Food pantry use increased by 43%, with community members requesting more fresh produce, meat, and dairy. The food desert triggered a 21% increase in home gardening and an 11% increase in home food preservation. CONCLUSIONS: Opening a Green Grocer offset only some of the effects of the food desert, because community members use it as a convenience store to purchase fresh produce and dairy products that families may lack before their next long-distance trip to a supermarket. Alderson's low-income residents now rely more heavily on food pantry assistance, while a small number of other residents have started gardening and food preservation. The first factor governing food acquisition behavior in rural Appalachia is food pricing, with the proximity of food access coming in second. How to overcome these two major barriers to food security in the midst of current economics and marketing remains to be answered.