Effect of Benidipine Alone and in Combination With Bosentan and Sildenafil in Amelioration of Pulmonary Arterial Hypertension in Experimental Model in Rats.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a persistent condition affecting the pulmonary arteries' endothelium. Benidipine, a calcium channel blocker, possesses vasodilatory, anti-inflammatory activity, reduces oxidative stress, and inhibits the activity of Transforming growth factor-ß (TGF-ß) and α-smooth muscle actin (α-SMA). The present study was designed to investigate the effect of benidipine alone and in combination with bosentan and sildenafil on monocrotaline (MCT)-induced pulmonary hypertension in a rat model. PAH was induced by a single-dose administration of MCT in rats. Animals were randomized into different groups and treated with benidipine alone and in combination with bosentan or sildenafil. Various parameters such as hemodynamic parameters, Fulton's index and oxidative stress parameters were performed. Additionally, histopathology of lung and right ventricular of heart tissue, immunohistochemistry, expression of α-SMA, endothelial nitric oxide synthase (eNOS), TGF-ß, and RT-PCR, and an in vitro study using human umbilical vein endothelial cells (HUVECs) was also carried out. Treatment of benidipine and its combination exhibited better prevention in the elevated right ventricular systolic pressure, right ventricular hypertrophy, rise in oxidative stress, and increase in expression of α-SMA and TGF-ß receptor 1 compared with MCT control group rats. In HUVECs, the expression of α-SMA was increased, whereas that of eNOS decreased after TGF-ß exposure and was substantially reversed after pretreatment with benidipine. We concluded that benidipine and its combination with bosentan and sildenafil exhibit beneficial effects in MCT-induced PAH through the eNOS/TGF-ß/α-SMA signaling pathway.

Targeting transcription factors through an IMiD independent zinc finger domain.

Immunomodulatory imide drugs (IMiDs) degrade specific C2H2 zinc finger degrons in transcription factors, making them effective against certain cancers. SALL4, a cancer driver, contains seven C2H2 zinc fingers in four clusters, including an IMiD degron in zinc finger cluster two (ZFC2). Surprisingly, IMiDs do not inhibit growth of SALL4 expressing cancer cells. To overcome this limit, we focused on a non-IMiD degron, SALL4 zinc finger cluster four (ZFC4). By combining AlphaFold and the ZFC4-DNA crystal structure, we identified a potential ZFC4 drug pocket. Utilizing an in silico docking algorithm and cell viability assays, we screened chemical libraries and discovered SH6, which selectively targets SALL4-expressing cancer cells. Mechanistic studies revealed that SH6 degrades SALL4 protein through the CUL4A/CRBN pathway, while deletion of ZFC4 abolished this activity. Moreover, SH6 led to significant 62% tumor growth inhibition of SALL4+ xenografts in vivo and demonstrated good bioavailability in pharmacokinetic studies. In summary, these studies represent a new approach for IMiD independent drug discovery targeting C2H2 transcription factors in cancer.

Non-covalent binding interaction of bioactive coumarin esculetin with calf thymus DNA and yeast transfer RNA: A detailed investigation to decipher the binding affinities, binding location, interacting forces and structural alterations at a molecular level.

Esculetin is a well-known coumarin derivative found abundantly in nature possessing an extensive array of pharmacological and therapeutic properties. Consequently, to comprehend its molecular recognition mechanism, our objective is to conduct a complete investigation of its interactions with the nucleic acid, specifically ct-DNA, and t-RNA, using spectroscopic and computational techniques. The intrinsic fluorescence of esculetin is quenched when it interacts with ct-DNA and t-RNA, and this occurs through a static quenching mechanism. The thermodynamic parameters demonstrated that the interaction is influenced by hydrogen bonding and weak van der Waals forces. CD and FT-IR results revealed no conformational changes in ct-DNA and t-RNA structure on binding with esculetin. Furthermore, competitive displacement assay with ethidium bromide, melting temperature, viscosity measurement, and potassium iodide quenching experiments, reflected that esculetin probably binds to the minor groove of ct-DNA. The molecular docking results provided further confirmation for the spectroscopic findings, including the binding location of esculetin and binding energies of esculetin complexes with ct-DNA and t-RNA. Molecular dynamics simulation studies demonstrated the conformational stability and flexibility of nucleic acids.

Interactions of Turmeric- and Curcumin-Functionalized Gold Nanoparticles with Human Serum Albumin: Exploration of Protein Corona Formation, Binding, Thermodynamics, and Antifibrillation Studies.

In order to better understand the bioavailability and biocompatibility of polyphenol-assisted surface-modified bioengineered nanoparticles in nanomedicine applications, here, we address a series of photophysical experiments to quantify the binding affinity of serum albumin toward polyphenol-capped gold nanoparticles. For this, two different gold nanoparticles (AuNPs) were synthesized via the green synthesis approach, where curcumin and turmeric extract act as reducing as well as capping agents. The size, surface charge, and surface plasmon bands of the AuNPs were highly affected by the adsorption of human serum albumin (HSA) during protein corona formation, which was investigated using dynamic light scattering (DLS), ξ-potential, ultraviolet-visible (UV-vis) spectroscopy, and transmission electron microscopy (TEM) measurements. Fluorescence-based methods, absorbance, and SERS experiments were carried out to evaluate the binding aspects of AuNPs with HSA. We found that the AuNPs show moderate binding affinity toward HSA (Kb ∼ 104 M-1), irrespective of the capping agents on the surface. Hydrophobic association, along with some contribution of electrostatic interaction, played a key role in the binding process. The binding interaction was more toward the subdomain IIA region of HSA, as indicated by the competitive displacement studies using site-specific binders (warfarin and flufenamic acid). Because of the large surface curvature of small-sized AuNPs, the secondary structural conformations of HSA were slightly altered, as revealed by circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopy, and surface-enhanced Raman scattering (SERS) measurements. Additionally, the findings of the binding interactions were re-evaluated using molecular dynamics (MD) simulation studies by determining the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), and changes in the binding energy of HSA upon complexation with AuNPs. To determine the tentative evidence for pharmacokinetic administration, these biocompatible AuNPs were applied to inhibit the amyloid fibril formation of HSA and monitored by using the thioflavin T (ThT) assay, ANS fluorescence assay, fluorescence microscopic imaging, and FESEM. AuNPs were found to show better resistance toward fibrillation of the adsorbed protein.

Facility assessment of the best functioning facility providing emergency obstetric care in the selected blocks of Varanasi, Uttar Pradesh.

Background: UP has the 2nd highest MMR which is 197 compared with national average of 113 (RGI-SRS-2016-2018).Although institutional deliveries in India has been increased from 78.9% (NFHS-4) to 89% (NFHS-5) [ UP from 67.8% to 83.4%] but still we are far away from SDG -3 target. It reflects that there may be increase in crude coverage but not in effective coverage. Materials and Methods: It is a cross sectional study conducted in May - June 2017. Out of 8 blocks of rural Varanasi, 4 blocks were selected randomly. Best functioning facility for EmOC services in each selected block were assessed using Facility Gap Assessment Schedule of IPHS. Result: None of the facility met the recommended standard for BEmOC .Tracking of drop out of ANC and PNC services, use of Partograph, treatment of abortion-related complications, were not found at all the 4 facility. Blood grouping and RH typing was also not functional at 2 of the 4 centers. Caesarean section and availability of blood bank were also lacking in CHC (FRU). Conclusion: If condition of best functioning facility in a block is not according to the recommendation then how can we expect to provide a good maternal health service to public.

Evaluation of the Effect of Vitamin D Levels During the Last Trimester of Pregnancy on Fetomaternal Outcomes in Patients With Preeclampsia.

Introduction Preeclampsia is a multisystem disorder with hypertension after 20 weeks of gestation. Among many predictors of preeclampsia, vitamin D being one of them is under many studies for establishing a correlation between levels of vitamin D and preeclampsia. Objective To observe a relation between vitamin D levels and preeclampsia and assess related fetomaternal outcomes. Method It is an observational study at the tertiary care center. One hundred twenty patients, out of which 60 were taken as cases with BP>140/90, and 60 were taken as controls with normal BP in a tertiary care center from January 1, 2020, to June 30, 2021. All investigations were sent, and the mode of delivery and the fetomaternal outcome were assessed. Results Compared to normal pregnant patients, preeclamptic patients have significantly lower levels of vitamin D with a p-value of <0.001, which is significant. Conclusion There is a relationship between vitamin D levels and preeclampsia. However, the effects of supplementation of vitamin D on fetomaternal outcomes need further studies.

SALL4B, not targeted by IMiD, is important for SALL4-mediated tumorigenesis.

Oncofetal transcription factor SALL4 is essential for cancer cell survival. 1-5 Recently, several groups reported that immunomodulatory imide drugs (IMiDs) could degrade SALL4 in a proteasome-dependent manner. 6,7 Intriguingly, we observed that IMiDs had no effect on SALL4-positive cancer cells. Further studies demonstrated that IMiDs could only degrade SALL4A, one of the SALL4 isoforms. This finding raises the possibility that SALL4B, the isoform not affected by IMiDs, may be essential for SALL4-mediated cancer cell survival. SALL4B knockdown led to an increase in apoptosis and inhibition of cancer cell growth. SALL4B gain-of-function alone led to liver tumor formation in mice. Our observation that protein degraders can possess isoform-specific effects exemplifies the importance of delineating drug action and oncogenesis at the isoform level to develop more effective cancer therapeutics.

The study of miRNA-200c expression and epithelial-to-mesenchymal transition-related transcription factors in the primary bladder urothelial carcinoma.

Background: Epithelial-mesenchymal transition (EMT) plays an important role in bladder carcinoma (BC) invasiveness and metastasis. Studies have shown that muscle-invasive BC (MIBC) and non-MIBC (NMIBC) are different at the molecular level owing to different EMT-related programming. Recent studies suggest that dysregulation of specific miRNAs is linked to EMT in BC. With this background, we aimed to study the immunoexpression of EMT-markers and its correlation with miRNA-200c expression in a series of MIBCs and NMIBCs. Materials and Methods: Quantitative real-time-polymerase chain reaction for the quantification of miR-200c expression was performed on 50 cases of urinary BC obtained from transurethral resection of bladder tumor (TURBT), cystectomy specimens, and ten peritumoral bladder tissue. Immunohistochemistry for ZEB1, ZEB2, TWIST, E-cadherin, and ß-catenin was performed on tumor and peritumoral bladder tissue. Results: Thirty-five TURBT and 15 cystectomy specimens were assessed. Among MIBC, loss of expression of E-cadherin (72.3%), ß-catenin (66.7%), and ZEB1, ZEB2, and TWIST2 immunoreactivity was noted in 53.3%, 86.7%, and 73.3% of cases, respectively. Among NMIBC, loss of expression of E-cadherin (22.5%), ß-catenin (17.1%) and ZEB1, ZEB2, and TWIST immunoreactivity was noted in 11.5%, 51.4%, and 91.4% of cases, respectively. Upregulation of miRNA-200c was noted in cases with retained E-cadherin and negative TWIST expression. Downregulation of miRNA-200c expression was noted in all the cases showing loss of E-cadherin, ß-catenin, and in cases immunoreactive for ZEB1, ZEB2, and TWIST in MIBC. Downregulation of miRNA-200c expression was also noted in cases of MIBC with retained ß-catenin and those immunonegative for ZEB1 and ZEB2. A similar trend was noted in NMIBC. Median miRNA-200c expression was low in both high-grade and low-grade NMIBC compared to peritumoral bladder tissue and was not statistically significant. Conclusion: This study for the first time explores the relation of miR200C with E-cadherin, b-catenin, and its direct transcriptional regulators, namely Zeb1, Zeb2, and Twist in the same cohort of BC. We observed that miRNA-200c is downregulated in both MIBC and NMIBC. We identified novel expression of TWIST in cases of BC showing downregulation of miR200Cs suggesting that it is one of the protein targets of altered miRNA-200c expression contributing to EMT and can serve as a promising diagnostic marker and therapeutic target. Loss of E-cadherin and ZEB1 immunoexpression in high-grade NMIBC suggests an aggressive clinical behavior. However, ZEB2 heterogeneous expression in BC limits its diagnostic and prognostic utility.

Efficient Biosorption of Hexavalent Chromium from Water with Human Hair.

The triphenyl group (trityl radical) possessing three-phenyl rings, self-assembled through aromatic π-π stacking interactions, can form interesting crystalline organic nano-flowers. In this work, we have synthesized a hybrid material of 1,2-bis(tritylthio)ethane and magnetite, which reduces toxic Cr(VI) to non-toxic Cr(III). We validated the efficacy of the hybrid in reducing toxic Cr(VI) along with three other adsorbent systems. Among the five adsorbent systems tested, we observed that human hair has higher Cr removal efficiency, which prompted us to explore further using different mechanical forms of human hair. Pulverized hair (PH), hair powder (HP), and raw hair (RH) were evaluated by employing different reaction factors such as the adsorbent dose, pH, initial Cr(VI) concentration, and contact time. The comparative evaluation showed that PH has greater adsorption capacity (15.14 mg/g), followed by RH (13.27 mg/g) and HP (10.5 mg/g). While investigating the adsorption mechanism, we observed that it follows pseudo-second-order kinetics suggesting chemisorption. The Freundlich isotherm model fitted well for Cr(VI) adsorption by human hair, suggesting a multi-layered adsorption process. Overall, this study promises a cost-effective and eco-friendly bio-adsorbent for Cr(VI), which may be scaled up to design automated industrial waste disposal systems.

Vulvar dermatoses-Can a pattern-based approach improve diagnostic yield?

BACKGROUND: Vulvar dermatoses (VD) pose a formidable challenge to clinicians and pathologists owing to various factors. The factors included are the histopathological heterogeneity of the vulva, moist and frictional environment, and the limited experience of gynecologists and general histopathologists in this field. To address this issue, the International Society for the Study of Vulvovaginal Disease (ISSVD) proposed a histopathological tissue reaction-based classification system for VD. Therefore, we attempted to study the utility of the 2006 ISSVD classification in reporting VD. We further evaluated if a dermatopathologist review could improve the diagnostic yield. MATERIALS AND METHODS: The vulvar biopsy reports (N = 106) were retrieved from histopathology case files, out of which benign non-infectious conditions (n = 55) were included in the study. The diagnosis retrieved from the case files was considered the initial diagnosis. Three dermatopathologists reviewed each biopsy, and a tissue reaction pattern/diagnosis was assigned as per ISSVD 2006, and this was considered a review diagnosis. The initial and review diagnoses were compared and analyzed. We further studied and analyzed the effect of the dermatopathologist's review on the diagnostic yield. RESULTS: The sclerotic pattern (34.6%) was the commonest tissue reaction pattern, followed by spongiotic (18%) and acanthotic patterns (14.5%) independently or in combination. The non-specific/descriptive report rate was significantly decreased following 2006 ISSVD and the dermatopathologist's review (83.6% vs.1.8%). CONCLUSION: Rendering tissue reaction patterns to vulvar biopsies will enable a comprehensive understanding of lesions and aid in clinically relevant reporting. In addition, dermatopathologists' review of difficult vulvar biopsies increases the diagnostic yield.

Status of Birth Preparedness and Complication Readiness of Pregnant Women and Recently Delivered Women in Rural Varanasi: Assessment of Current Scenario.

Background: Birth Preparedness and Complication Readiness is practise of planning for events related to child birth and making necessary arrangements, so that timely and adequate medical care can be provided to the mother. Objective: The objective of the study was to assess the Birth Preparedness and Complication Readiness of pregnant and recently delivered women in rural areas of Varanasi. Materials and Methods: A total of 633 pregnant and recently delivered women were interviewed using 11 components related to antenatal care and preparations done for child birth. Results: Out of all the respondents, less than half (46.4%) among Pregnant women and nearly the same proportion (45.1%) among recently delivered women were found "Well Prepared." Conclusion: The study revealed that there is a need to create awareness among the people about the importance of proper planning and making arrangements in advance to avert the danger to the life of mother and child.

Molecular Characterization of IDH Wild-type Diffuse Astrocytomas: The Potential of cIMPACT-NOW Guidelines.

IDH wild-type (wt) grade 2/3 astrocytomas are a heterogenous group of tumors with disparate clinical and molecular profiles. cIMPACT-NOW recommendations incorporated in the new 2021 World Health Organization (WHO) Classification of Central Nervous System (CNS) Tumors urge minimal molecular criteria to identify a subset that has an aggressive clinical course similar to IDH -wt glioblastomas (GBMs). This paper describes the use of a panel of molecular markers to reclassify IDH -wt grade 2/3 diffuse astrocytic gliomas (DAGs) and study median overall survival concerning for to IDH -wt GBMs in the Indian cohort. IDH -wt astrocytic gliomas (grades 2, 3, and 4) confirmed by IDHR132H immunohistochemistry and IDH1/2 gene sequencing, 1p/19q non-codeleted with no H3F3A mutations were included. TERT promoter mutation by Sanger sequencing, epidermal growth factor receptor amplification, and whole chromosome 7 gain and chromosome 10 loss by fluorescence in situ hybridization was assessed and findings correlated with clinical and demographic profiles. The molecular profile of 53 IDH -wt DAGs (grade 2: 31, grade 3: 22) was analyzed. Eleven cases (grade 2: 8, grade 3: 3) (20.75%) were reclassified as IDH -wt GBMs, WHO grade 4 ( TERT promoter mutation in 17%, epidermal growth factor receptor amplification in 5.5%, and whole chromosome 7 gain and chromosome 10 loss in 2%). Molecular GBMs were predominantly frontal (54.5%) with a mean age of 36 years and median overall survival equivalent to IDH -wt GBMs (18 vs. 19 mo; P =0.235). Among grade 2/3 DAGs not harboring these alterations, significantly better survival was observed for grade 2 versus grade 3 DAGs (25 vs. 16 mo; P =0.002). Through the incorporation of a panel of molecular markers, a subset of IDH -wt grade 2 DAGs can be stratified into molecular grade 4 tumors with prognostic and therapeutic implications. However, IDH -wt grade 3 DAGs behave like GBMs irrespective of molecular profile.

Pregnancy outcomes and vertical transmission capability of SARS-CoV-2 infection among asymptomatic females: A cross-sectional study in a tertiary care rural hospital.

BACKGROUND: The COVID-19 pandemic is still spreading throughout the world along with its strange and frightening mutations, and the World Health Organization (WHO) has declared it as a global pandemic. OBJECTIVE: The present investigation aims to evaluate the effect of SARS-CoV-2 infection on mother and newborn outcomes and the vertical transmission potential of this virus. STUDY DESIGN: This was a cross-sectional study conducted at a tertiary care dedicated COVID-19 hospital. A total of 40 pregnant females (RT-PCR positive for SARS-CoV-2) and their 41 neonates (including stillbirths and a twin delivery) were included in the present study. RESULTS: All the mothers in the study were SARS-CoV-2 positive on the RT-PCR test, but none had any COVID-19 symptoms (pneumonia-like fever, cough, fatigue, sore throat, shortness of breath, and diarrhea). Out of 41 newborns, 38 (92.7%) were healthy, one (2.4%) was a stillbirth, and two newborns (4.9%) could not be revived. All the 41 (100.0%) neonates, including stillborn and preterm were negative for the SARS-CoV-2 RT-PCR test. Twenty-Six neonates (63.4%) were delivered by caesarean section, whereas 15 cases (36.6%) had a normal vaginal delivery. CONCLUSION: The present study showed no suggestion of vertical transmission of SARS-CoV-2 in pregnant females. Therefore, the placenta might function as a barrier to the SARS-CoV-2 virus. Also, there were no complications come upon during the delivery of any neonate in the present study.

Targeting an Inducible SALL4-Mediated Cancer Vulnerability with Sequential Therapy.

Oncofetal protein SALL4 is critical for cancer cell survival. Targeting SALL4, however, is only applicable in a fraction of cancer patients who are positive for this gene. To overcome this limitation, we propose to induce a cancer vulnerability by engineering a partial dependency upon SALL4. Following exogenous expression of SALL4, SALL4-negative cancer cells became partially dependent on SALL4. Treatment of SALL4-negative cells with the FDA-approved hypomethylating agent 5-aza-2'-deoxycytidine (DAC) resulted in transient upregulation of SALL4. DAC pretreatment sensitized SALL4-negative cancer cells to entinostat, which negatively affected SALL4 expression through a microRNA, miRNA-205, both in culture and in vivo. Moreover, SALL4 was essential for the efficiency of sequential treatment of DAC and entinostat. Overall, this proof-of-concept study provides a framework whereby the targeting pathways such as SALL4-centered therapy can be expanded, sensitizing cancer cells to treatment by transient target induction and engineering a dependency. SIGNIFICANCE: These findings provide a therapeutic approach for patients harboring no suitable target by induction of a SALL4-mediated vulnerability.

Successful Multimodality Management of Atypical Teratoid/Rhabdoid Tumour of the Lower Dorsal Spine with Spinal Drop Metastasis: Illustrated Review.

INTRODUCTION: Spinal atypical teratoid/rhabdoid tumour (AT/RT) is exquisitely rare and constitutes 2% of all AT/RTs. CASE PRESENTATION: A 6-year-old boy presented with low backache for the last 5 months. MRI of the spine showed a 1.5 × 1.5 × 4.7 cm intradural extramedullary mass extending from D10 to D12, causing compression of the conus medullaris. With a preoperative diagnosis of ependymoma, a gross total resection (GTR) of tumour was performed. Post-operative histopathology showed AT/RT. The tumour cells were immunopositive for cytokeratin, epithelial membrane antigen, smooth muscle actin, and p53 and immunonegative for MIC2, desmin, glial fibrillary acidic protein, and INI1. Post-operative neuraxis MRI revealed post-operative changes (D10-D12) with a 9 mm enhancing lesion at L5-S1 junction suggesting drop metastasis. There was no lesion in brain. Cerebrospinal fluid cytology did not show any malignant cell. The metastatic work-up was normal. He received 3 cycles of chemotherapy with ICE regimen (ifosfamide, carboplatin, and etoposide). Subsequently, he received craniospinal irradiation (CSI)-36 Gy/20 fractions/4 weeks followed by focal boost to primary tumour bed and spinal drop metastasis-14.4 Gy/8 fractions/1.5 weeks. Thereafter, he received 3 more cycles of ICE regimen. End-of-treatment MRI spine showed post-op changes (D10-D12) and 38.9% reduction of the L5-S1 lesion suggesting partial response. Six monthly spinal MRI showed serial reduction of the metastatic lesion leading to complete response (CR) 1 year after completion of treatment. On last follow-up (30 months from the initial diagnosis), he was neurologically intact and in CR. CONCLUSION: Multimodality management comprising GTR of tumour, CSI followed by focal boost, and multiagent chemotherapy (ICE) can lead to successful outcome in patients with this rare and aggressive spinal tumour.

mTOR pathway activation in focal cortical dysplasia.

BACKGROUND: Focal cortical dysplasia (FCD) is a localized cortical malformation and considerable morphological overlap exists between FCD IIB and neurological lesions associated with Tuberous sclerosis complex (TSC). Abnormal mTOR pathway secondary to somatic mTOR mutation and TSC gene mutation linked to PI3K/AKT/mTOR pathway have supported the hypothesis of common pathogenesis involved. Role of converging pathway, viz. Wnt/ß-Catenin and mTOR is unknown in FCD. We aimed to analyse FCD IIB for TSC1/TSC2 mutations, immunoreactivity of hamartin, tuberin, mTOR and Wnt signalling cascades, and stem cell markers. MATERIALS AND METHODS: Sixteen FCD IIB cases were retrieved along with 16 FCD IIA cases for comparison. Immunohistochemistry was performed for tuberin, hamartin, mTOR pathway markers, markers of stem cell phenotype, and Wnt pathway markers. Mutation analysis for TSC1 and TSC2 was performed by sequencing in 9 FCD cases. RESULTS: All FCD cases showed preserved hamartin and tuberin immunoreactivity. Aberrant immunoreactivity of phospho-P70S6 kinase, S6 ribosomal, phospho-S6 ribosomal and Stat3 was noted in FCD IIB, with variable phospho-4E-BP1 (45%) and absent phospho-Stat3 expression. Immunoreactivity for phospho-P70S6 kinase (100%), S6 ribosomal protein (100%) and Stat3 (100%) was noted in FCD IIA, but not for phospho-S6 ribosomal, phospho-4E-BP1 and phospho-Stat3. c-Myc immunoreactivity was noted in all FCD cases. Nestin (81%) and Sox 2 (88%) stained balloon cells in FCD IIB (44%), while in FCD IIA cases were negative. All FCD cases were immunopositive for Wnt, but were negative for ß-Catenin and cyclin-D1. TSC mutations were detected in two cases of FCD IIB. CONCLUSION: Abnormal mTOR pathway activation exists in FCD IIB and IIA, however, shows differential immunoreactivity profile, indicating varying degrees of dysregulation. Labelling of neuronal stem cell markers in balloon cells suggests they are phenotypically immature. TSC1/2 mutation play role in the pathogenesis of FCD. Deep targeted sequencing is preferred diagnostic technique since conventional sanger sequencing often fails to detect low-allele frequency variants involved in mTOR/TSC pathway genes, commonly found in FCD.

Semi-quantitative F-18-FDG PET/computed tomography parameters for prediction of grade in patients with renal cell carcinoma and the incremental value of diuretics.

OBJECTIVE: The primary objective of the study was to evaluate the correlation between semi-quantitative F-18 FDG PET parameters and renal cell carcinoma (RCC) grade and its role in predicting the histopathological grade in RCC. The secondary objective was to evaluate the role of forced diuresis in improving the diagnostic accuracy of F-18 FDG for RCC. METHODS: Thirty-three patients with radiologically proven RCC were included in the study. All patients underwent PET/CT on a dedicated PET/CT scanner (Biograph mCT; Siemens Medical Solutions, Erlangen, Germany) 45-60 min post-injection F-18-FDG. Patients were then injected 1 mg/kg body weight furosemide (upto 40 mg) and regional PET/CT images of abdomen were acquired after 2 h. For both baseline and post-diuretic F-18-FDG PET/CT scans, maximum standardized uptake value for tumor (SUVmax), mean SUV for tumor, metabolic tumor volume (MTV), tumor-to-liver (T/L) and tumor-to-kidney ratio (T/K) were calculated. Histopathology findings were considered as the reference standard. To assess the incremental value of diuresis in scan interpretation, visual analysis of scans was done. RESULTS: Of 33 patients, histopathology grading was available for comparison with metabolic tumor markers in all except four. Of 29 patients (mean age = 51.89 ± 13.54 years), 20 patients had clear cell (cc) type while rest had non-cc RCC. Difference between the mean values among the categories was insignificant for all parameters except T/K. Fuhrman grading was obtained in 25 patients (17 low and eight high). SUVmax, MTV and T/L were found to be significantly different between low and high grade patients. Significantly strong positive correlation was observed between Furhman grades and tumor metabolism (r ≥ 0.5). No significant difference was observed between baseline and post-diuretic scan in any of the patients. CONCLUSION: Semi-quantitative F-18 FDG PET parameters (SUVmax, MTV and T/L) were found to be significantly correlated with Fuhrman grade in patients with RCC and are important markers for differentiation between low- and high-grade tumors. Furthermore, forced diuresis had no incremental value in characterization of primary RCC lesions.

Renal detection of Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi in malaria associated acute kidney injury: a retrospective case-control study.

OBJECTIVE: Acute kidney injury (AKI) is a frequent presentation in malaria infections. Several cases of AKI that are accompanied by clinical symptoms of malaria infection, such as fever, nausea, respiratory distress, and anemia remain undiagnosed due to challenges in accurate diagnosis using peripheral blood microscopy and rapid diagnostic tests that are currently used in clinical settings. This is particularly true for P. vivax and P. knowlesi infections. As a result, these patients are not able to receive anti-malarial therapy in a timely manner. The objective of the present study was to investigate if patients presenting with AKI harbored any of the five human Plasmodium species (P. falciparum, P. vivax, P. knowlesi, P. malariae, and P. ovale) within their renal tissues. RESULTS: We found that renal biopsies from malaria associated AKI patients harbor the human malaria parasites P. falciparum, P. vivax and P. knowlesi as mono- and mixed species infections. Presence of microvascular injury in a majority of the malaria associated AKI cases suggested vascular involvement of P. vivax and P. knowlesi. This research note also highlights P. knowlesi as an emerging pathogen in the Indian subcontinent.

Low-Grade Fibromyxoid Sarcoma of the External Auditory Canal: A Rare Pathology and Unusual Location.

Low-grade fibromyxoid sarcoma (LGFMS) is an enigmatic soft tissue tumor. It frequently presents as a deeply seated mass in the proximal extremities and trunk. Superficial LGFMSs of the head and neck are exceedingly rare. Hyalinizing spindle cell tumor with giant rosettes (HSTGR) is an entity considered to be on the histologic spectrum of LGFMS. We present a case of a 44-year-old female who presented with a superficial, polypoid mass of the external auditory meatus. Microscopic examination revealed the classic histologic features of HSTGR. To our knowledge, this case is the first described at this extremely unusual location. Identification and reporting of such unusual cases is important to understand and compare the behavior of superficial LGFMS to that of the more common deeply seated tumors.