Indocyanine green and methylene blue dye guided sentinel lymph node biopsy in patients with penile cancer (PeCa): results of 50 inguinal basins assessed at a single institution in India.

AIM: The primary aim of this study was to validate the reliability, sensitivity and safety profile of novel combination of ICG- methylene blue dye as an SN tracer for PeCa. METHODS: This is a validation and non-randomised prospective observational study involving 25 patients (50 inguinal basins) who underwent SLNB where in ICG and methylene blue were used for localisation. The patients with clinically node negative groins were recruited in the study. SNs were identified intraoperatively using near infrared fluorescence imaging (NIRF Imaging system, SPY-PHI, Stryker, Sweden) and blue dye. The numbers of SNs identified by each tracer and the rates of complications and nodal recurrence during the followup. RESULTS: Overall 137 SNs were identified intraoperatively. Among the 137 SNs excised fluorescence, blue dye and Combined (blue + green) identified 57(41.6%), 27 (19.7%), and 51 (37.2%), respectively. The average number of SLNs removed per patient was 5 (range, 1-11) with sentinel lymph nodes detection rate at 94% (47/50). Seven patients had malignancy on SLNB and underwent ipsilateral radical inguinal lymphadenectomy. One patient had false negative SN and positive node in modified inguinal lymphadenectomy specimen. No adverse events were observed in all cases. CONCLUSION: The Novel combination of ICG fluorescence-Methylene blue dye technique is simple, reliable and safe. Moreover, it demonstrates a high SLN detection rate with a low false-negative rate, and it avoids radiation exposure.

Vogt striae: Demystified.

Background: To study the correlation of different variables of Vogt striae to other attributes of keratoconus and to suggest a new grading system for Vogt striae to exactly represent the configuration and extent in each individual keratoconic cornea. Methods: The study was an observational and data review study. A total of 386 eyes of 207 keratoconus patients were screened from February 2016 to August 2018. Patients with prior history of collagen cross linking were excluded from the study as measurement of corneal thickness is less reliable for many months after collagen cross linking, and patients may have superficial corneal striae and scarring after collagen cross linking. Patients with history or clinical features suggestive of corneal hydrops or who had undergone lamellar or full thickness corneal transplants and intracorneal ring segments were also excluded from the study. Results: Of total 52 eyes with Vogt striae, 31 eyes (59.6%) had vertical orientation, 3 (5.8%) had horizontal, 11 (21.2%) had oblique while 7 eyes (13.5%) had mixed orientation of Vogt striae. Mean uncorrected distance visual acuity (UCVA) in the vertical group was 0.76 logMAR, horizontal group was 0.80 logMAR, oblique group was 0.65 logMAR, and mixed group was 1.17 logMAR units. Corneal scarring was present in 15 eyes (28.8%) and absent in 37 (71.2%) eyes with Vogt striae. In the mixed Vogt striae group, 85.7% eyes (6 eyes of 7) had corneal scarring, while 16.1% in vertical group (5 eyes of 31), and 27.3% in oblique group (3 of 11) had corneal scarring. Based on three attributes of Vogt striae, that is orientation, number, and corneal scarring, a new grading for Vogt striae was also suggested. Conclusion: This is the first study to report the presence of mixed Vogt striae (combination of horizontal and/or vertical and/or oblique Vogt striae in a single cornea) in cases of keratoconus. For the first time, oblique Vogt striae have been described, and clear limits have been set to call it horizontal, oblique, or vertical striae. A new grading for Vogt striae is also suggested.

Ayurvedic Management of Presbycusis (Project TOPMAC): Protocol for an Exploratory Randomized Controlled Trial.

BACKGROUND: Presbycusis is characterized by sensorineural hearing loss in both ears at high frequencies, which affects more than half of the older adults by the age of 75 years and is often accompanied by tinnitus and cognitive deterioration. Unfortunately, there are no treatments available to restore hearing loss. Treatment mainly focuses on improving the quality of life and communication with hearing aids. Traditional medicine like Ayurveda also explains ailments of a similar nature as Badhirya and advises using drugs with antiaging and neuroprotective activity for treatment. In Ayurveda, Badhirya and Karnanada (senile deafness with tinnitus) are due to vitiation of Vata Dosha. Treatments such as topical oil pooling (Karnapurana) are usually advised to counter Vata, improve hearing capacity, and reduce tinnitus. Kshirabala Taila, a medicated oil formulation prepared with Sida cordifolia Linnaeus, is one of the most preferred oils for topical oil pooling in such conditions, as it has a definitive indication for sensory dysfunctions. Drugs like Withania somnifera (L.) Dunal (Ashwagandha) are also used, as they ameliorate neurodegeneration and help to improve cognitive dysfunction. OBJECTIVE: We propose an exploratory randomized controlled trial study for evaluating the efficacy of TOPMAC (Topical Oil Pooling with Kshirabala Taila and Supplementation of Ashwagandha Churna) in tinnitus suppression and hearing and cognitive function protection in patients aged 60-75 years with mild to moderate presbycusis. METHODS: A parallel, 2-group, exploratory randomized controlled trial will be conducted in an Indian Ayurvedic research center at its outpatient service. Participants (N=60) with mild to moderate presbycusis will be recruited by screening. Participants will be randomized (computer-generated 1:1) to receive either basic treatment and health education (BTHE) or BTHE+TOPMAC for 24 weeks. The primary objective is to compare the efficacy of TOPMAC with that of BTHE in the protection of hearing function. The secondary objective is to compare the efficacy of TOPMAC with that of BTHE in tinnitus suppression and cognitive function protection. RESULTS: This project was funded in January 2023. The institutional ethics committees at National Ayurveda Research Institute for Panchakarma (3/1/2020/NARIP/Tech/2036) and Institute for Communicative and Cognitive Neuro Sciences (IEC006) approved this study. The first patient was enrolled in September 2023; 22 participants were enrolled as of August 2024. The data analysis is yet to start, and the results are expected to be published by January 2025. CONCLUSIONS: If this exploratory trial is proven effective, it will steer the setting of a definitive randomized controlled trial to test whether the TOPMAC intervention can be incorporated as a cost-effective integrative approach for managing presbycusis. The Indian government has already launched a National Program for Prevention and Control of Deafness to benefit the deaf population. TOPMAC may later be considered for integration with the national program. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2023/04/051485; https://tinyurl.com/2h2hry3n. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55089.

Accurate low and high grade glioma classification using free water eliminated diffusion tensor metrics and ensemble machine learning.

Glioma, a predominant type of brain tumor, can be fatal. This necessitates an early diagnosis and effective treatment strategies. Current diagnosis is based on biopsy, prompting the need for non invasive neuroimaging alternatives. Diffusion tensor imaging (DTI) is a promising method for studying the pathophysiological impact of tumors on white matter (WM) tissue. Single-shell DTI studies in brain glioma patients have not accounted for free water (FW) contamination due to tumors. This study aimed to (a) assess the efficacy of a two-compartment DTI model that accounts for FW contamination and (b) identify DTI-based biomarkers to classify low-grade glioma (LGG) and high-grade glioma (HGG) patients. DTI data from 86 patients (LGG n = 39, HGG n = 47) were obtained using a routine clinical imaging protocol. DTI metrics of tumorous regions and normal-appearing white matter (NAWM) were evaluated. Advanced stacked-based ensemble learning was employed to classify LGG and HGG patients using both single- and two-compartment DTI model measures. The DTI metrics of the two-compartment model outperformed those of the standard single-compartment DTI model in terms of sensitivity, specificity, and area under the curve of receiver operating characteristic (AUC-ROC) score in classifying LGG and HGG patients. Four features (out of 16 features), namely fractional anisotropy (FA) of the edema and core region and FA and mean diffusivity of the NAWM region, showed superior performance (sensitivity = 92%, specificity = 90%, and AUC-ROC = 90%) in classifying LGG and HGG. This demonstrates that both tumorous and NAWM regions may be differentially affected in LGG and HGG patients. Our results demonstrate the significance of using a two-compartment DTI model that accounts for FW contamination by improving diagnostic accuracy. This improvement may eventually aid in planning treatment strategies for glioma patients.

TinyML-Raman: A novel IoT based field-deployable spectra analysis for accurate identification of pharmaceuticals and trace dye-pesticide mixtures from facile SERS method.

BACKGROUND: Upcoming inexpensive, compact Internet of Things (IoT) microcontrollers i.e., tiny-machine learning (TinyML) takes the ML driven Raman spectroscopy one step ahead for realization of more affordable and highly compact field deployable instruments. Further, lack of large spectral datasets and need for numerous specialized SERS substrates impede the development of various ML-based surface enhanced Raman spectroscopy (SERS) applications. The aim is to introduce TinyML analysis on wide range of spectra classes using customized dataset obtained with low-cost SERS. In this regard, it is vital to establish an optimum ML model and efficient data handling methodology for low memory TinyML units. RESULTS: We introduce a novel TinyML methodology for accurate classification of large spectra classes with smartphone assistance for data communication and results visualization. To generate large customized spectral dataset, we present a facile, micro-drop SERS using Au colloids and reusable grooved Al substrates. The results demonstrated that memory efficient 8-bit data quantization based convolutional neural network is effective for accurate identification of 22 different spectra classes of trace dye-pesticide mixtures and pharmaceuticals. In this novel quantized data analysis on significantly varied intensity and complex variation spectra classes i.e., many individual, binary-mixtures and some with varied compositions, data normalization is shown to be powerful for improving ML classification accuracy from about 55 % to >99.5 %. Its robustness is demonstrated using inter-instrument driven data variations such as spectral shifts, high noise, and abscissa-flip, with five-fold cross validation of model performance. In addition, on-site quantification of analyte through spectral intensity is also demonstrated. SIGNIFICANCE: This study opens up a new approach of ML analysis towards realization of next generation field deployable analytical instruments maintaining data privacy. It presents a detailed procedure of quantized spectral data analysis and its implementation in TinyML, attractive for various users and instrument manufacturers. The presented innovative computer-free ML analysis can be employed in all types of spectrometers, meeting the common goal of Raman spectroscopy i.e., accurate identification of complex spectra classes.

Management of patients with Reflex Vasovagal syncope with a protocol involving a yoga maneuver Tadasana.

BACKGROUND: There is no universally followed protocol for managing Reflex Vasovagal syncope (VVS). METHODS: VVS patients were treated with a 2 step protocol. Step I - counseling, hydration, physiotherapy, and Tadasana Yoga maneuver. Patients with ≥2 VVS recurrences were given step II care - intensification of step I, elastic stockings,and pharmacotherapy. Follow-up included assessment by periodic functional status questionnaires. RESULTS: 157 patients (103 males & 54 females,mean age - 53 ± 20 years & mean LVEF - 62 ± 5%.) experienced 867 total events - 382 syncopal, and 485 near syncopal episodes over 14 ± 9 months. After step I protocol, the mean total, syncopal and near syncopal events declined from 5 ± 7 to 0.3 ± 1.2 (P < 0.0001), 3 ± 2 to 0.1 ± 0.4 (P < 0.0001) and 3 ± 6 to 0.2 ± 1.1 (P < 0.0001) respectively. Twenty (12.7%) patients had 53 event recurrences, 15- syncopal episodes in 7 and 38 near syncope events in 13. After step II, 5 patients had 14 events. At 33 ± 15 months, in 152 patients (96.8%) there were no recurrences and syncope was prevented in all (100%). The median total, syncopal and near syncopal events declined from 3 to 0,(p < 0.001) 2 to 0 (p < 0.001) and 1 to 0 (p < 0.001) respectively. There was an improvement in all the 3 quality of life parameters. CONCLUSION: We demonstrate a simple and effective protocol that can be universally adopted to prevent VVS recurrences,with improvement in quality of life.

Parkinsonism following bilateral chronic subdural hematoma that presented as orthostatic headache: Highlighting clinical pearls for family physicians and physiotherapists.

Chronic subdural hematoma (CSDH) is a great mimicker. It should be considered in anyone presenting with chronic headaches that show postural variation. Parkinsonism following CSDH, while known, is only rarely reported in the literature. Hyponatremia, rapid correction of hyponatremia, medications, and mechanical pressure are thought to be risk factors. Here, we report a case of a 61-year-old male diagnosed with bilateral CSDH managed by craniotomy and clot evacuation who developed parkinsonism. We share several learnings (clinical pearls) that emerged from the close collaboration and co-learning curve between a family physician and physiotherapist involved in home-based rehabilitation. In conclusion, while managing the postoperative course of patients with CSDH, clinicians should maintain a high index of suspicion for parkinsonism. Early recognition and appropriate management with syndopa with supportive physiotherapy results in significant improvement of function and quality of life. Notably, parkinsonism following SDH is transient and nonprogressive and may not require lifelong therapy.

A qualitative exploration of patients' perception regarding the comprehensive dental services availed at a primary health center.

Introduction: Comprehensive oral care is a service centered around the patient, and individuals who need it the most often face limited access. Patient perception acts as a guide for enhancing quality, ensuring patients' future intent to utilize the services and facilitating recommendations to others. The present study aimed to assess the patients' perception of comprehensive dental services availed at a Primary Health Center (PHC). Methods: This qualitative study was based on a phenomenological interpretive approach, and judgment sampling method was employed. A validated interview guide, developed from relevant literature was employed in the local language to conduct interviews among adults visiting the PHC, gathering their views regarding the services provided. The interviews were audio recorded on a digital voice recorder, and files were password protected. Content saturation guided the determination of the final number of participants interviewed. After translating and transcribing the interviews, thematic analysis and coding were performed using ATLAS. ti 23 for Windows. Results: A total of 12 participants were included in the study, following data saturation. Among them, there were 8(66.7%) female and 4(33.3%) male participants. Ten overarching main themes were discerned through the assigned codes, including positive views, neutral views, negative views, previous dental clinics visited, previous experience with dental treatment, treatments sought at the center, referrals, source of information about the dental center, subsequent visits and suggestions for improvement. Conclusions: The findings of this study revealed a positive patient perception of the comprehensive dental services offered at the PHC. Through insightful interviews, various strengths, and areas for improvement regarding the center and care provision were identified. These insights provide valuable suggestions that can be applied to elevate the utilization of dental services, ensuring continuous improvement in patient care.

Anxiety-, and depression-like behavior following short-term finasteride administration is associated with impaired synaptic plasticity and cognitive behavior in male rats.

Finasteride, a 5α-Reductase inhibitor, is used to treat male pattern baldness and benign prostatic hyperplasia. Several clinical studies show that chronic finasteride treatment induces persistent depression, suicidal thoughts and cognitive impairment and these symptoms are persistent even after its withdrawal. Previous results from our lab showed that repeated administration of finasteride for six days induces depression-like behavior. However, whether short-term finasteride administration induces anxiety-like behavior and memory impairment and alters synaptic plasticity are not known, which formed the basis of this study. Finasteride was administered to 2-2.5 months old male Wistar rats for six days and subjected to behavioral evaluation, biochemical estimation and synaptic plasticity assessment. Anxiety-like behavior was evaluated in the elevated plus maze (EPM), open field test (OFT), light/dark test (LDT), and novelty suppressed feeding test (NSFT), and learning and memory using novel object recognition test (NORT) and novel object location test (NOLT) and depression-like behavior in the sucrose preference test (SPT). Synaptic plasticity in the hippocampal Schaffer collateral-CA1 was evaluated using slice field potential recordings. Plasma corticosterone levels were estimated using ELISA. Finasteride administration induced anxiety-like behavior in the EPM, OFT, LDT and NSFT, and depression-like behavior in the SPT. Further, finasteride induced hippocampal dependent spatial learning and memory impairment in the NOLT. In addition, finasteride decreased basal synaptic plasticity and long-term potentiation (LTP) in the hippocampus. A trend of increased plasma corticosterone levels was observed following repeated finasteride administration. These results indicate the potential role of corticosterone and synaptic plasticity in finasteride-induced effects and further studies will pave way for the development of novel neurosteroid-based therapeutics in neuropsychiatric diseases.

Advances in Hierarchical Inorganic Nanostructures for Efficient Solar Energy Harvesting Systems.

The urgent need to address the global energy and environmental crisis necessitates the development of efficient solar-power harvesting systems. Among the promising candidates, hierarchical inorganic nanostructures stand out due to their exceptional attributes, including a high specific surface area, abundant active sites, and tunable optoelectronic properties. In this comprehensive review, we delve into the fundamental principles underlying various solar energy harvesting technologies, including dye-sensitized solar cells (DSSCs), photocatalytic, photoelectrocatalytic (water splitting), and photothermal (water purification) systems, providing a foundational understanding of their operation. Thereafter, the discussion is focused on recent advancements in the synthesis, design, and development of hierarchical nanostructures composed of diverse inorganic material combinations, tailored for each of these solar energy harvesting systems. We meticulously elaborate on the distinct synthesis methods and conditions employed to fine-tune the morphological features of these hierarchical nanostructures. Furthermore, this review offers profound insights into critical aspects such as electron transfer mechanisms, band gap engineering, the creation of hetero-hybrid structures to optimize interface chemistry through diverse synthesis approaches, and precise adjustments of structural features. Beyond elucidating the scientific fundamentals, this review explores the large-scale applications of the aforementioned solar harvesting systems. Additionally, it addresses the existing challenges and outlines the prospects for achieving heightened solar-energy conversion efficiency.

Probing avoided crossings and conical intersections by two-pulse femtosecond stimulated Raman spectroscopy: Theoretical study.

This study leverages two-pulse femtosecond stimulated Raman spectroscopy (2FSRS) to characterize molecular systems with avoided crossings (ACs) and conical intersections (CIs) in their low-lying excited electronic states. By simulating 2FSRS spectra of microscopically inspired ACs and CIs models, we demonstrate that 2FSRS not only delivers valuable information on the molecular parameters characterizing ACs and CIs but also helps distinguish between these two systems.

Grossing to reporting of Wilms tumor with emphasis on proper sampling in treatment-naive and postchemotherapy specimens and their clinicopathological correlation with outcome.

Context: Emphasis on grossing to reporting for the assessment of histopathological parameters predicting outcomes in Wilms tumor. Aims: To analyze various clinicopathological parameters that effect outcomes in treatment naïve and post chemotherapy Wilms tumor specimens. Settings and Design: This was a retrospective observational study. Subjects and Methods: All patients diagnosed with Wilms tumor between 2012 and 2018 at our institute will be included with their clinical findings, laboratory reports, and radiological findings. The patients will be categorized into two groups based on treatment protocol (Society of Pediatric Oncology (SIOP) or the National Wilms Tumor Study Group/Children's Oncology Group (COG) guidelines) used. Details of Grossing and reporting protocols used for the in pre treatment and post treatment specimens will be analyzed. Follow-up till December 2020 will be analyzed. Statistical Analysis Used: Chi-square and Fisher's exact tests were used for statistical analysis. Results: A total of 36 patients with the diagnosis of Wilms tumor were included in the present study. The mean age of presentation was 3.9 ± 0.7 years, and males were more common than females. Most of them presented as abdominal mass and few with isolated hematuria. Twenty-six (72%) patients were treated under SIOP protocol with preoperative neoadjuvant chemotherapy. Ten patients underwent upfront surgery as per COG protocol. In SIOP group patients, the mean tumor size was 9.3cm. Forty percent (n = 10) we mixed histological type followed by blastemal type constituting (32%, n = 8). Regressive and epithelial histological types constituted 16% (n = 4) and 12% (n = 3), respectively. In the SIOP group 72% (n = 19) had no anaplasia and 28% (n = 7) had anaplasia. Fifty seven percent (n = 15) cases were Stage I, followed by 26.9% n = 7) and 11.5% (n = 3) being Stage II and Stage III, respectively. Ten patients underwent upfront surgery as per COG protocol. The mean tumor size among this group was 8 cm ranging from 7 cm to 11 cm. Eight (80%) cases had favorable histology and two cases showed focal anaplasia. Heterologous differentiation is seen in 3 (70%). Out of the 10 cases, one case was Stage I, six were Stage 2, one was Stage III, and two were clinical Stage IV. None of the cases showed either vessel or lymph node metastasis. All the patients received adjuvant chemotherapy postsurgery and were followed up till December 2020 for (at least 3 years). Of 25 patients in the SIOP group, 18 (72%) had complete remission with no radiological evidence of residual disease. Of the 10 patients in the COG group, 6 (70%) had complete remission. Conclusions: Histopathological evaluation of Wilms tumor is a critical aspect in the management of Wilms tumor, as tumor characteristics are different in the tumors treated under SIOP and COG protocols, which will ultimately affect the prognostic risk stratification. This necessitates the knowledge of the important grossing and reporting of these tumors under the two protocols.

Boron-doped graphene topological defects: unveiling high sensitivity to NO molecule for gas sensing applications.

Global air quality has deteriorated significantly in recent years due to large emissions from the transformation industry and combustion vehicles. This issue requires the development of portable, highly sensitive, and selective gas sensors. Nanostructured materials, including defective graphene, have emerged as promising candidates for such applications. In this work, we investigated the B-doped topological line defect in graphene as a sensing material for various gas molecules (CO, CO2, NO, and NH3) based on a combination of density functional theory and the non-equilibrium Green's function method. The electronic transport calculations reveal that the electric current can be confined to the line defect region by gate voltage control, revealing highly reactive sites. The B-doped topological line defect is metallic, favoring the adsorption of NO and NH3 over CO and CO2 molecules. We notice changes in the conductance after gas molecule adsorption, producing a sensitivity of 50% (16%) for NO (NH3). In addition, the recovery time for nitride gases was calculated for different temperatures and radiation frequencies. At 300 K the ultraviolet (UV) has a fast recovery time compared to the visible (VIS) one by about two orders of magnitude. This study gives an understanding of how engineering transport properties at the microscopic level (by topological line defect and chemical B-doping) leads to promising nanosensors for detecting nitride gas.

Interventions to promote cost-effectiveness in adult intensive care units: consensus statement and considerations for best practice from a multidisciplinary and multinational eDelphi study.

BACKGROUND: There is limited evidence to guide interventions that promote cost-effectiveness in adult intensive care units (ICU). The aim of this consensus statement is to identify globally applicable interventions for best ICU practice and provide guidance for judicious use of resources. METHODS: A three-round modified online Delphi process, using a web-based platform, sought consensus from 61 multidisciplinary ICU experts (physicians, nurses, allied health, administrators) from 21 countries. Round 1 was qualitative to ascertain opinions on cost-effectiveness criteria based on four key domains of high-value healthcare (foundational elements; infrastructure fundamentals; care delivery priorities; reliability and feedback). Round 2 was qualitative and quantitative, while round 3 was quantitative to reiterate and establish criteria. Both rounds 2 and 3 utilized a five-point Likert scale for voting. Consensus was considered when > 70% of the experts voted for a proposed intervention. Thereafter, the steering committee endorsed interventions that were identified as 'critical' by more than 50% of steering committee members. These interventions and experts' comments were summarized as final considerations for best practice. RESULTS: At the conclusion of round 3, consensus was obtained on 50 best practice considerations for cost-effectiveness in adult ICU. Finally, the steering committee endorsed 9 'critical' best practice considerations. This included adoption of a multidisciplinary ICU model of care, focus on staff training and competency assessment, ongoing quality audits, thus ensuring high quality of critical care services whether within or outside the four walls of ICUs, implementation of a dynamic staff roster, multidisciplinary approach to implementing end-of-life care, early mobilization and promoting international consensus efforts on the Green ICU concept. CONCLUSIONS: This Delphi study with international experts resulted in 9 consensus statements and best practice considerations promoting cost-effectiveness in adult ICUs. Stakeholders (government bodies, professional societies) must lead the efforts to identify locally applicable specifics while working within these best practice considerations with the available resources.

Grossing and reporting of radical prostatectomy specimens: An evidence-based approach.

Radical prostatectomy (RP) constitutes the primary treatment option for patients with clinically localized, biopsy-proven prostate cancer that requires local treatment with curative intent. Accurate reporting of radical prostatectomy specimens is required to guide further risk stratification and management of patients. Hence, for the handling and reporting of RP specimens, a standardized protocol should be followed. Many general pathologists may not be well-versed with the guidelines for the handling of radical prostatectomy specimens. This article discusses a detailed approach to grossing techniques, including specimen description, fixation requirements, gross cut-up, and reporting of the grade and stage of RP specimens. This will enable the pathologist to aid in multidisciplinary management.