Search

Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is a type of inherited cancer syndrome with a genetic predisposition to different types of cancer. There is an increased predisposition to cancers in the endometrium, colon, stomach, ovary, uterus, skin, kidney, and brain in patients of Lynch syndrome. We are reporting a 48-year-old male who presented with a pea-sized growth in his left arm which was found to be sebaceoma on histopathology. On further detailed history, examination, and genetic study, it was proved to be a familial case of Lynch syndrome. The case is being reported to stress the importance of knowledge about clinical manifestation, associated neoplasms, and molecular genetic profile of Lynch syndrome which will enable physicians and pathologists to provide highly targeted surveillance and management for patients with high cancer risk.

PURPOSEHereditary breast and ovarian cancer (HBOC) syndrome is primarily characterized by mutations in the BRCA1/2 genes. There are several barriers to the implementation of genetic testing and counseling in India that may affect clinical decisions. These consensus recommendations were therefore convened as a collaborative effort to improve testing and management of HBOC in India.DESIGNRecommendations were developed by a multidisciplinary group of experts from the Indian Society of Medical and Pediatric Oncology and some invited experts on the basis of graded evidence from the literature and using a formal Delphi process to help reach consensus. PubMed and Google Scholar databases were searched to source relevant articles.RESULTSThis consensus statement provides practical insight into identifying patients who should undergo genetic counseling and testing on the basis of assessments of family and ancestry and personal history of HBOC. It discusses the need and significance of genetic counselors and medical professionals who have the necessary expertise in genetic counseling and testing. Recommendations elucidate requirements of pretest counseling, including discussions on genetic variants of uncertain significance and risk reduction options. The group of experts recommended single-site mutation testing in families with a known mutation and next-generation sequencing coupled with multiplex ligation probe amplification for the detection of large genomic rearrangements for unknown mutations. Recommendations for surgical and lifestyle-related risk reduction approaches and management using poly (ADP-ribose) polymerase inhibitors are also detailed.CONCLUSIONWith rapid strides being made in the field of genetic testing/counseling in India, more oncologists are expected to include genetic testing/counseling as part of their clinical practice. These consensus recommendations are anticipated to help homogenize genetic testing and management of HBOC in India for improved patient care.

A 24-year-old female presented with wasting and weakness of both hands and fasciculations over the chin since 12 years, followed by imbalance while walking and speech changes since 10 years. Her 12-year-old sister also had a similar clinical presentation. There were fasciculations over the chin, tongue, hands, back, thighs with wasting and weakness in tongue, and C7, C8, T1 segments in both upper limbs along with bipyramidal signs. There was limb and gait ataxia. Magnetic resonance imaging brain showed pancerebellar atrophy, and electromyography was suggestive of anterior horn cell involvement in bulbar, cervical, thoracic, and lumbar segments. Next-generation sequencing identified a novel likely pathogenic deletion mutation: chr6:152527389_152527399del, c.22711_22721del, and p.Ala7571ArgfsTer4 in exon 125 of synaptic nuclear envelope protein 1 (SYNE1) gene. This mutation leads to frameshift and premature termination of the protein 'Nesprin 1'. Amyotrophic lateral sclerosis-like presentation followed by cerebellar ataxia have been described with SYNE1 ataxia. This unique phenotype and novel deletion mutation of SYNE1 gene is the first case reported from India.

Electrical storm (ES) is a life threatening clinical situation. Though a few clinical pointers exist, the occurrence of ES in a patient with remote myocardial infarction (MI) is generally unpredictable. Genetic markers for this entity have not been studied. In the present study, we carried out genetic screening in patients with remote myocardial infarction presenting with ES by next generation sequencing and identified 25 rare variants in 19 genes predominantly in RYR2, SCN5A, KCNJ11, KCNE1 and KCNH2, CACNA1B, CACNA1C, CACNA1D and desmosomal genes - DSP and DSG2 that could potentially be implicated in electrical storm. These genes have been previously reported to be associated with inherited syndromes of Sudden Cardiac Death. The present study suggests that the genetic architecture in patients with remote MI and ES of unstable ventricular tachycardia may be similar to that of Ion channelopathies. Identification of these variants may identify post MI patients who are predisposed to develop electrical storm and help in risk stratification.

Defective autophagy has been linked to lipotoxicity in several cellular models. We aimed to investigate autophagy in lipid-stimulated hepatoma (Huh7) cells and tested whether 4-phenyl butyric acid (4-PBA), a chemical chaperone, has a beneficial role in hepatic fat accumulation and lipotoxicity. We report that long-term (24 h) exposure of hepatocytes to palmitate block autophagic flux that leads to lipid accumulation and cell death. Western blotting analysis showed increased accumulation of SQSTM1/p62, and decreased expression of Beclin1 and Atg7 in palmitate-treated cells. Autophagy inhibition by 3-methyladenine (3-MA) in palmitate-treated cells neither increased SQSTMI/p62 accumulation nor cell death, thus suggesting complete blockade of autophagy by palmitate. 4-PBA reduced lipid accumulation and cell death that were associated with restoration of autophagy. siRNA-mediated knockdown of Atg7 and presence of autophagy inhibitors, 3-MA and chloroquine, resulted in the decrease in lipid-lowering effect of 4-PBA, suggesting that 4-PBA mediates its lipid-lowering effect via autophagy. Apoptotic parameters, including altered Bcl2:Bax ratio and PARP1 cleavage induced by palmitate, were improved by 4-PBA. Our results indicate that palmitate impairs autophagy and increases lipid accumulation in Huh7 cells, whereas 4-PBA plays a protective role in lipid accumulation and lipotoxicity through activation of autophagy.

The present study investigates the possible anti-nociceptive effect of intraperitoneal (i.p.) honokiol: a phenolic compound originally isolated from Magnolia officinalis, in acute and chronic inflammatory pain models. Doses of 0.1, 5, and 10 mg/kg honokiol were administered in carrageenan induced pain and the dose (honokiol 10 mg/kg i.p.) with most significant response among behavioral tests was selected for further experiments. The i.p. administration of honokiol inhibits mechanical hyperalgesia, mechanical allodynia, and thermal hyperalgesia, without causing any apparent toxicity. To elucidate the effect of honokiol on various cytokines and antioxidant enzymes, quantitative real-time-PCR was performed to determine the expression levels of pro-inflammatory cytokines and antioxidant enzymes. It is demonstrated that honokiol significantly reduced the expression levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF). Similarly, honokiol was also found to potentiate the expression of nuclear factor erythroid 2–related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), and heme oxygenase-1 (HO-1) levels. Additionally, honokiol significantly reduced plasma nitrite levels as compared to complete Freund’s adjuvant (CFA) induced group. X-ray analysis and hematoxylin and eosin (H&E) staining of inflamed and treated paws showed that honokiol reduced the inflammation with significantly less leukocyte infiltration and soft tissue inflammation. In order to explore the possible mechanism of action of honokiol, agonists [piroxicam (5 mg/kg), tramadol (50 mg/kg), and gabapentin (5 mg/kg) i.p.] as well as antagonists [naloxone (4 mg/kg), olanzapine (10 mg/kg), and flumazenil (0.2 mg/kg) i.p.] were used to study involvement of various receptors on the anti-nociceptive effect of honokiol. The potential side effects of honokiol on muscle activity were assessed. An adverse effect testing of honokiol by liver and renal functions were also carried out. The effect of oral honokiol was also assessed on gastrointestinal (GIT) mucosa. Our results demonstrate that honokiol has a significant anti-nociceptive activity through inhibition of anti-inflammatory mediators.

ZFYVE27 (Protrudin) was originally identified as an interacting partner of spastin, which is most frequently mutated in hereditary spastic paraplegia. ZFYVE27 is a novel member of FYVE family, which is implicated in the formation of neurite extensions by promoting directional membrane trafficking in neurons. Now, through a yeast two-hybrid screen, we have identified that ZFYVE27 interacts with itself and the core interaction region resides within the third hydrophobic region (HR3) of the protein. We confirmed the ZFYVE27's self-interaction in the mammalian cells by co-immunoprecipitation and co-localization studies. To decipher the oligomeric nature of ZFYVE27, we performed sucrose gradient centrifugation and showed that ZFYVE27 oligomerizes into dimer/tetramer forms. Sub-cellular fractionation and Triton X-114 membrane phase separation analysis indicated that ZFYVE27 is a peripheral membrane protein. Furthermore, ZFYVE27 also binds to phosphatidylinositol 3-phosphate lipid moiety. Interestingly, cells expressing ZFYVE27(ΔHR3) failed to produce protrusions instead caused swelling of cell soma. When ZFYVE27(ΔHR3) was co-expressed with wild-type ZFYVE27 (ZFYVE27(WT)), it exerted a dominant negative effect on ZFYVE27(WT) as the cells co-expressing both proteins were also unable to induce protrusions and showed cytoplasmic swelling. Altogether, it is evident that a functionally active form of oligomer is crucial for ZFYVE27 ability to promote neurite extensions.

Abstract With the current development of the 5G infrastructure, there presents a unique opportunity for the deployment of battery-less mmWave reflect-array-based sensors. These fully-passive devices benefit from having a larger detectability than alternative battery-less solutions to create self-monitoring megastructures. The presented ‘smart’ skin sensor uses a Van-Atta array design enabling ubiquitous local strain monitoring for the structural health monitoring of composite materials featuring wide interrogation angles. Proof-of-concept prototypes of these ‘smart’ skin millimeter-wave identification tags, that can be mounted on or embedded within common materials used in wind turbine blades, present a highly-detectable radar cross-section of − 33.75 dBsm and − 35.00 dBsm for mounted and embedded sensors respectively. Both sensors display a minimum resolution of 202 $$\upmu $$ μ -strain even at 40 $$^{\circ }$$ ∘ off-axis enabling interrogation of the fully-passive sensor at oblique angles of incidence. When interrogated from a proof-of-concept reader, the fully-passive, sticker-like mmID enables local strain monitoring of both carbon fiber and glass fiber composite materials. The sensors display a repeatable and recoverable response over 0–3000 $$\upmu $$ μ -strain and a sensitivity of 7.55 kHz/ $$\upmu $$ μ -strain and 7.92 kHz/ $$\upmu $$ μ -strain for mounted and embedded sensors, respectively. Thus, the presented 5G-enabled battery-less sensor presents massive potential for the development of ubiquitous Digital Twinning of composite materials in future smart cities architectures.

Abstract Lead (Pb) halide perovskite solar cells (PSCs) exhibit impressive power conversion efficiencies close to those of their silicon counterparts. However, they suffer from moisture instability and Pb safety concerns. Previous studies have endeavoured to address these issues independently, yielding minimal advancements. Here, a general nanoencapsulation platform using natural polyphenols is reported for Pb‐halide PSCs that simultaneously addresses both challenges. The polyphenol‐based encapsulant is solution‐processable, inexpensive (≈1.6 USD m−2), and requires only 5 min for the entire process, highlighting its potential scalability. The encapsulated devices with a power conversion efficiency of 20.7% retained up to 80% of their peak performance for 2000 h and up to 70% for 7000 h. Under simulated rainfall conditions, the encapsulant rich in catechol groups captures the Pb ions released from the degraded perovskites via coordination, keeping the Pb levels within the safe drinking water threshold of 15 ppb.

Organic solar cells (OSCs) are becoming increasingly popular in the scientific community because of their many desirable properties. These features include solution processability, low weight, low cost, and the ability to process on a wide scale using roll-to-roll technology. Enhancing the efficiency of photovoltaic systems, particularly high-performance OSCs, requires study into not only material design but also interface engineering. This study demonstrated that two different types of OSCs based on the PTB7-Th:IEICO-4F and PM6:Y6 active layers use a ZnO bilayer electron transport layer (ETL). The ZnO bilayer ETL comprises a ZnO nanoparticle (ZnO NP) and a ZnO layer created from a sol-gel. The effect of incorporating ZnO NPs into the electron transport layer (ETL) was studied; in particular, the effects on the electrical, optical, and morphological properties of the initial ZnO ETL were analyzed. The ability of ZnO films to carry charges is improved by the addition of ZnO nanoparticles (NPs), which increase their conductivity. The bilayer structure had better crystallinity and a smoother film surface than the single-layer sol-gel ZnO ETL. This led to a consistent and strong interfacial connection between the photoactive layer and the electron transport layer (ETL). Therefore, inverted organic solar cells (OSCs) with PTB7-Th:IEICO-4F and PM6:Y6 as photoactive layers exhibit improved power conversion efficiency and other photovoltaic properties when using the bilayer technique.