Detection of HbD Punjab Trait in Saurashtra Region of Gujarat by HPLC Method.

The HbD Punjab trait is a less common hemoglobin variant in the Saurashtra region of Gujarat. This patient presented to the General Medicine and Biochemistry Department at All India Institute of Medical Sciences, Rajkot, Hospital, for the HbA1c analysis by high-performance liquid chromatography (HPLC). The patient was 52 years old, a known case of type 2 diabetes mellitus and hypertension, and presented with complaints of generalized malaise and fatigability for the previous ten to twelve months. On physical examination, there was no evidence of pallor, lymphadenopathy, splenomegaly, or hepatomegaly. Peripheral blood smear revealed normocytic normochromic RBC, and platelets were adequate and normal in morphology. The HPLC analysis revealed heterozygous for hemoglobin D (HbD Punjab trait), and false high HbA1c corresponds to fasting plasma glucose (FPG) levels due to abnormal separation. However, genetic counseling is highly recommended to detect any potential reproductive risk factors.

Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems.

In recent years, there has been a notable surge in the utilization of stabilized bile acid liposomes, chemical conjugates, complexes, mixed micelles, and other drug delivery systems derived from bile acids, often referred to as bilosomes. The molecular structure and interactions of these amphiphilic compounds provide a distinctive and captivating subject for investigation. The enhanced stability of new generation bilosomes inside the gastrointestinal system results in the prevention of drug degradation and an improvement in mucosal penetration. These characteristics render bilosomes to be a prospective nanocarrier for pharmaceutical administration, prompting researchers to investigate their potential in other domains. This review paper discusses bilosomes that have emerged as a viable modality in the realm of drug delivery and have significant promise for use across several domains. Moreover, this underscores the need for additional investigation and advancement in order to comprehensively comprehend the prospective uses of bilosomes and their effectiveness in the field of pharmaceutical administration. This review study explores the current scholarly attention on bilosomes as prospective carriers for drug delivery. Therapeutic areas where bilosomes have shown outstanding performance in terms of drug delivery are outlined in the graphical abstract.

A Retrospective Study Comparing the Surgical Results of Platysma Myocutaneous Flap, Buccal Pad of Fat, and Nasolabial Flap for Reconstruction After Fibrotomy in Cases of Oral Submucous Fibrosis.

PURPOSE: To evaluate the effectiveness of nasolabial flap (NLF), a buccal pad of fat flap (BFP), and platysma myocutaneous flap (PMF) for reconstruction following fibrotomy for individuals with oral submucous fibrosis (OSMF). MATERIAL AND METHOD: A retrospective study was conducted among patients diagnosed with grade III and IV OSMF in the Department of Oral and Maxillofacial Surgery at Sharad Pawar Dental College between January 2016 and August 2018. The essential patient information was obtained from the Medical Record Department (MRD) at Acharya Vinoba Bhave Rural Hospital (AVBRH), Datta Meghe Institute of Medical Sciences (DMIMS) Sawangi (Meghe) Wardha. The patients were categorized into three groups: the NLF, the BFP, and the PMF groups. Each group had 16 patients, and factors such as interincisal width, diminished burning sensation in the mouth, inter-commissure distance, and flap necrosis were compared pre- and post-operatively. Student's unpaired t-test and chi-square test were employed for statistical analysis. RESULT: Mean interincisal mouth-opening increased from pre-operative 4.79 to 41.42 mm post-operatively in the NLF group, BFP group from 6 to 39.42 mm and in the PMF group from 9.26 to 39.34 mm with p value=0.0001. NLF group showed complete and partial resolution of the burning sensation of the mouth at 93.75% and 6.25%, BFP at 62.25% and 32.75% while in PMF it was 68.5% and 31.25% respectively. One year postoperatively 3.28 mm increase in inter-commissure width was observed in the NLF group with a marginal increase in the PMF group and a negligible increase in the BFP group. 18.75% partial flap necrosis was seen in BFP, 18.75% in the PMF group, and 6.25% in the NFL group. CONCLUSION: All the flaps are efficacious in treating OSMF, however, NLF stands ahead with its higher reliability owing to its excellent blood supply.

Optimisation and in-vivo evaluation of extracted Karanjin loaded liposomal topical formulation for treatment of psoriasis in tape-stripped mouse model.

AIM: The present work is focus on development of anti-psoriasis activity of Karanjin (isolated from Pongamia pinnata seed oil) loaded liposome based lotion for enhancement of skin permeation and retention. METHOD: Karanjin was isolated using liquid-liquid extraction method and characterised by HPLC analysis and partition coefficient. Further, isolated Karanjin was loaded into liposomes using thin-film hydration technique and optimised by Box-Behnken design. Selected optimised batch was characterised their mean diameter, PDI, zeta potential, and entrapment efficiency, morphology (by TEM), FTIR and ex-vivo skin retention. Additionally, Karanjin loaded liposomes were formulated into lotion and characterise their rheological, spreadability, texture, ex-vivo skin permeation & retention, stability and anti-psoriatic activity in mouse tail model. RESULT: The yield of Karanjin from seed oil was 0.1% w/v and have lipophilic nature. The optimised liposomal formulation showed 195 ± 1.8 nm mean diameter, 0.271 ± 0.02 PDI, -27.0 ± 2.1 mV zeta potential and 61.97 ± 2.5% EE. TEM image revel the spherical shap of liposome surrounded by single phospholipid bilayer and no interection between drug and excipients. Further, lotion was prepared by 0.1% w/v carbopol and found to 615 mPa.sec viscosity, good thixotropic behaviour, spreadability and texture. There was 22.44% increase in drug permeation for Karanjin loaded liposomal lotion compared to pure Karanjin lotion, confirm by ex-vivo permeation and retention. While, in-vivo study revel the liposomal lotion of Karanjin was found to have 16.09% higher drug activity then 5% w/w conventional Karanjin lotion. CONCLUSION: Karanjin loaded liposomal lotion have an effective anti-psoriatic agent and showed better skin permeation and retention than the conventional Karanjin lotion.

Evaluation of Laboratory Performance in Consideration with Pre analytical and Post analytical Quality Indicators.

Implementation of Quality indicators (QIs) plays an imperative role in improving the total testing process, as it provides a quantitative basis for evaluating the laboratory performance. Besides monitoring of analytical quality specifications, several lines of experimental and clinical evidence have alluded a pivotal role of extra-analytical phases in improving the quality of laboratory services and therefore a relevance of pre- and post-analytical steps have been speculated on the overall quality in the total testing process and consequently on clinical decision-making. This was a retrospective study designed to evaluate and review different extra-analytical quality indicators in NABL accredited clinical biochemistry laboratory at BJ Medical College and Civil Hospital, Ahmedabad, Gujarat in an endeavour to ameliorate the performance of the laboratory. All Clinical Chemistry Laboratory test requests with their respective samples from January 2018 to December 2021 were included in the study. A total of 1,439,011samples were processed, and were evaluated for seven QIs [(% of number of suitable samples not received; QI-8), (% of number of samples received in inappropriate container; QI-9), (% of number of samples hemolysed; QI-10), (% of number of samples with inadequate sample volume; QI 12) (% of number of samples received mismatched; QI 15), (% of number of samples reported after turnaround time; QI 21) and (% of number of samples with critical values informed; QI 22)] based on defined criteria of Quality Specification given by International Federation of Clinical Chemistry. Total number of preanalytical errors was 53,669 (3.72%). Among the preanalytical errors, inadequate sample volume (2.37% of total samples; 63.49% of total pre-analytical errors) was the most common anomaly followed by Not received samples (24.18%) hemolysis (8.26%) mismatched (3.91%) and 0.14% samples were received in Inappropriate container; manifesting that the error frequency was unacceptable for QI 21 and QI 8, acceptable for QI 10, minimally acceptable for QI 15 and optimum for QI QI 9. Furthermore, there was year-wise progressive decline in error rate of inadequate sample volume, hemolysed sample received and mismatched samples. Total number of post analytical errors were 19,002 (1.32%). TAT outlier and critical values communicated were the two QIs evaluated for this phase and results of both QI were within acceptable limits. Quality indicators serve as a tool to monitor process performance and consequently derived error rates warrant active intervention to improve the laboratory services and patient health care. Dissemination of certified documents, regular staff training and evaluation needs to be conducted.

Eugenol-Loaded Transethosomal Gel for Improved Skin Delivery and Treatment of Atopic Dermatitis.

Atopic dermatitis is a skin condition characterized by lichenification (thickening and increased skin marking), eczematous lesions, dry skin, itching, and pruritus. Eugenol is an aromatic polyphenolic compound that has attracted the attention of researchers due to its anti-inflammatory, anti-oxidant, and anti-cancer properties. The primary goal of the present study was to develop and evaluate eugenol-loaded transethosomes for the treatment of AD. Eugenol-loaded transethosomes were formulated using the ethanol injection method and subsequently subjected to particle size analysis, zeta potential, entrapment efficiency, deformability index, and HRTEM analysis. Transethosomal gel was prepared by direct-dispersion method by using Carbopol 940®. Results showed transethosomes to be lipid bilayer structures with acceptable size, and high entrapment efficiency. Transethosomal formulation showed shear-thinning behavior. Eugenol-loaded transethosomal gel was significantly able to enhance the retention of the drug in the skin. Transethosomal gel was significantly able to reduce Ear thickness, DLC, TLC, and IL-6 levels in mice model of AD. These results indicate that the eugenol-loaded transethosomal gel could be a promising carrier for the topical administration of eugenol for the treatment of AD.

All-endoscopic approach for distal biceps tendon pathology: analysis of long-term outcomes in partial and complete ruptures.

BACKGROUND: Distal biceps tendon (DBT) pathology is a spectrum that ranges from tendinopathy to complete retracted ruptures, and surgical treatment is usually performed via open approaches. The purpose of this study was to analyze safety and long-term outcomes of all-endoscopic surgery for entire spectrum of primary DBT pathology. The hypothesis was that at an all-endoscopic technique would result in satisfactory clinical outcomes and a low complication rate. METHODS: Consecutive patients who underwent all-endoscopic surgery for primary isolated DBT pathology (bursitis, partial and acute/chronic complete tears) between January 2013 and December 2021 were assessed and analyzed retrospectively. Refractory bursitis and low-grade partial tears underwent endoscopic débridement, and high-grade partial tears and complete ruptures underwent all-endoscopic repair or graft reconstruction. Preoperative and follow-up assessment included functional assessment using Mayo Elbow Performance Score and a Patient-Reported Distal Biceps Score, and radiological assessment was performed using plain biplanar radiographs and sonography. Pre- and postoperative scores for the overall group, and for partial and complete tears, were compared using a paired t test. RESULTS: Overall, 26 male patients underwent an all-endoscopic surgery for DBT tears; the pathology was classified by endoscopic findings into 6 types, and follow-up period ranged from 21 to 125 months (mean 79.4 months). Nine chronic partial tears (35%) included predominantly bursitis (type I, n = 2) and predominantly partial tears (type IIA and B, n = 7). The complete tear group (65%) included isolated short or long head tears (type IIIA and IIIB, n = 2) and complete tendon ruptures (types IV, V, and VIA-C, n = 15). Endoscopic débridement of the bursitis/low-grade tears and repair of the high-grade and complete ruptures resulted in complete resolution of symptoms and significant improvement in both Mayo Elbow Performance Score and Patient-Reported Distal Biceps Score (P < .001). Autografts were necessary in 35% (6/17) of complete tears, and no significant difference was found in functional scores in this group as compared to those where primary repairs were possible. There were 2 minor complications (7.6%) that involved transient lateral antebrachial cutaneous nerve neuropraxia. Follow-up sonography and radiographs showed an intact tendon and absence of heterotopic ossification or synostosis. CONCLUSIONS: An all-endoscopic approach for treating DBT pathology was safe and reliable and was associated with significant improvement in subjective and functional outcomes in the long-term. The dual-anchor onlay repair technique showed long-term radiologically demonstrable structural integrity of the tendon and was associated with a low minor complication rate and absence of heterotopic ossification.

Endoscopic anterior capsulectomy for severe elbow contractures.

Elbow stiffness secondary to trauma or surgical reconstruction can sometimes result in a severe contracture with restricted joint space, and arthroscopic access to the joint is difficult. Previous surgery and severe stiffness can also alter the position of neurovascular structures and iatrogenic injury is possible with an inside-out arthroscopic approach. To overcome these technical difficulties, an endoscopic approach to the anterior capsule can be performed as an alternative to open approach. The endoscopic approach utilises the sub-brachialis space for an outside-in capsular resection under vision. Identification of standard anatomic landmarks is useful as a guide for safe resection in a central to peripheral direction.

Exploring the therapeutic potential of naturally occurring piceatannol in non-communicable diseases.

Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.

Experimental design approach for development of carboplatin loaded chitosan modified liposomal formulation with improved topical vaginal therapeutic potential.

One of the most prevalent cancers affecting women globally is cervical cancer. Cervical cancer is thought to cause 570 000 new cases annually, and standard treatments can have serious side effects. In this work, the main aim is to design, fabrication, and evaluation of carboplatin loaded chitosan coated liposomal formulation (CCLF-I) for vaginal delivery in the treatment of cervical cancer. The particle size and polydispersity index of the CCLF-1 were observed at 269.33 ± 1.15 and 0.40 ± 0.002 nm, respectively. The in vitro mucin binding studies showed good adhesiveness of CCLF-I as compared to plain liposomes (CPLF-I), which was found at 23.49 and 10.80%, respectively. The ex-vivo percent drug permeation from plain liposomal formulation (CPLF-I) was found to be higher in comparison to chitosan coated liposomal formulation which was 56.33% while in CCLF-I it was observed 47.32% this is due to, higher retainability of delivery system (CCLF-I) on targeted site attained by coating of mucoadhesive polymer on liposomes. Ex vivo tissue retention studies exhibited 24.2% of CCLF-I in comparison to 10.34% from plain drug formulation (CPLF-I). The in vivo vaginal retention studies exhibited 14% of drug retention after 24 h from the novel formulation in comparison to 6% from the plain formulation. The developed CCLF-I formulation would open a new avenue in the cervical treatment.

Relevance of augmented kisspeptin signaling through H364 KISS1R in central precocious puberty.

Understanding the pathophysiology of idiopathic central precocious puberty (ICPP) is essential, in view of its consequences on reproductive health and metabolic disorders in later life. Towards this, estimation of circulating levels of the neuropeptides, viz; Kisspeptin (Kp-10), Neurokinin B (NKB) and Neuropeptide Y (NPY), acting upstream to Gonadotropin-Releasing Hormone (GnRH), has shown promise. Insights can also be gained from functional studies on genetic variations implicated in ICPP. This study investigated the pathophysiology of ICPP in a girl by exploring the therapeutic relevance of the circulating levels of Kp-10, NKB, NPY and characterizing the nonsynonymous KISS1R variant, L364H, that she harbours, in a homozygous condition. Plasma levels of Kp-10, NKB and NPY before and after GnRH analog (GnRHa) treatment, were determined by ELISA. It was observed that GnRHa treatment resulted in suppression of circulating levels of Kp-10, NKB and NPY. Further, the H364 variant in KISS1R was generated by site directed mutagenesis. Post transient transfection of either L364 or H364 KISS1R variant in CHO cells, receptor expression was ascertained by western blotting, indirect immunofluorescence and flow cytometry. Kp-10 stimulated signalling response was also determined by phospho-ERK and inositol phosphate production. Structure-function studies revealed that, although the receptor expression in H364 KISS1R was comparable to L364 KISS1R, there was an enhanced signalling response through this variant at high doses of Kp-10. Thus, elevated levels of Kp-10, acting through H364 KISS1R, contributed to the manifestation of ICPP, providing further evidence that dysregulation of Kp-10/KISS1R axis impacts the onset of puberty.

An insight into biosensing platforms used for the diagnosis of various lung diseases: A review.

Many of the infectious diseases are ubiquitous in nature and pose a threat to global and public health. The original cause for such type of serious maladies can be summarized as the scarcity of appropriate analysis and treatment methods. Pulmonary diseases are considered one of the life-threatening lung diseases that affect millions of people globally. It consists of several types, namely, asthma, lung cancer, tuberculosis, chronic obstructive pulmonary disease, and several respiratory-related infections. This is due to the limited access to well-equipped healthcare facilities for early disease diagnosis. This needs the availability of processes and technologies that can help to stop this harmful disease-diagnosing practice. Various approaches for diagnosing various lung diseases have been developed over time, namely, autopsy, chest X-rays, low-dose CT scans, and so forth. The need of the hour is to develop a rapid, simple, portable, and low-cost method for the diagnosis of pulmonary diseases. So nowadays, biosensors have been becoming one of the highest priority research areas as a potentially useful tool for the early diagnosis and detection of many pulmonary lung diseases. In this review article, various types of biosensors and their applications in the diagnosis of lung-related disorders are expansively explained.

How does dynamic arthroscopic tracking compare with radiologic glenoid track for identification of on- and off-track lesions in anterior shoulder instability?

BACKGROUND: Current treatment paradigms for anterior shoulder instability are based on radiologic measurements of glenohumeral bone defects, and mathematical calculation of the glenoid track (GT) is used to classify lesions into on-track and off-track morphology. However, radiologic measurements have shown high variability, and GT widths under dynamic conditions have been reported to be significantly smaller than those under static radiologic conditions. The purpose of this study was to assess the reliability, reproducibility, and diagnostic validity of dynamic arthroscopic standardized tracking (DAST) in comparison to the gold-standard radiologic track measurement method for the identification of on- and off-track bony lesions in patients with anteroinferior shoulder instability. METHODS: Between January 2018 and August 2022, 114 patients with traumatic anterior shoulder instability were evaluated using 3-T magnetic resonance imaging or computed tomography scans; glenoid bone loss, Hill-Sachs interval, GT, and Hill-Sachs occupancy ratio (HSO) were measured, and defects were classified as on-track or off-track defects and peripheral-track defects (based on HSO percentage) by 2 independent researchers. During arthroscopy, a standardized method (DAST method) was used by 2 independent observers to classify defects into on-track defects (central and peripheral) and off-track defects. Interobserver reliability of the DAST and radiologic methods was calculated using the κ statistic and reported as percentage agreement. Diagnostic validity (sensitivity, specificity, positive predictive value, and negative predictive value) of the DAST method was calculated using the radiologic track (HSO percentage) as the gold standard. RESULTS: The radiologically measured mean glenoid bone loss percentage, Hill-Sachs interval, and HSO in off-track lesions were lower with the arthroscopic method (DAST) as compared with the radiologic method. The DAST method showed nearly perfect agreement between the 2 observers for the on-track/off-track classification (κ = 0.96, P < .001) and the on-track central or peripheral /off-track classification (κ = 0.88, P < .001). The radiologic method showed greater interobserver variability (κ = 0.31 and κ = 0.24, respectively) with only fair agreement for both classifications. Inter-method agreement varied between 71% and 79% (95% confidence interval, 62%-86%) between the 2 observers, and reliability was assessed as slight (κ = 0.16) to fair (κ = 0.38). Overall, for identification of an off-track lesion, the DAST method showed maximum specificity (81% and 78%) when radiologic peripheral-track lesions (HSO percentage of 75%-100%) were considered off-track and showed maximum sensitivity when arthroscopic peripheral-track lesions were classified as off-track. CONCLUSION: Although inter-method agreement was low, a standardized arthroscopic tracking method (DAST method) showed superior interobserver agreement and reliability for lesion classification in comparison to the radiologic track method. Incorporating DAST into current algorithms may help reduce variability in surgical decision making.

Assessment of Serum Fucose Level among Oral Squamous Cell Carcinoma Patients: A Case-Control Study.

Background: Serum glycoproteins, which are made up of various monosaccharides, are altered in malignancy, a disorder of cellular conduct. L-fucose, a methyl pentose that serves as the last sugar in the majority of plasma glycoproteins, is one of the monosaccharides. Numerous illness conditions and cancers have been linked to increased levels of protein-bound fucose. Materials and Methods: In the current study, the serum fucose levels of patients with oral squamous cell carcinoma (OSCC) and healthy individuals were assessed and compared. The present study included a total of 30 OSCC patients and 30 healthy controls. The Winzler method was used to estimate the serum L-fucose levels using a spectrophotometer (Spectronic 20, Thermo Fisher Scientific, USA). Results: Age and sex had no effect on serum fucose levels. In contrast to healthy individuals, OSCC patients' mean serum fucose levels significantly increased. In conclusion, patients with OSCC can benefit from the use of serum fucose as an investigative biomarker.

Progress in drug delivery and diagnostic applications of carbon dots: a systematic review.

Carbon dots (CDs), which have particle size of less than 10 nm, are carbon-based nanomaterials that are used in a wide range of applications in the area of novel drug delivery in cancer, ocular diseases, infectious diseases, and brain disorders. CDs are biocompatible, eco-friendly, easy to synthesize, and less toxic with excellent chemical inertness, which makes them very good nanocarrier system to deliver multi-functional drugs effectively. A huge number of researchers worldwide are working on CDs-based drug delivery systems to evaluate their versatility and efficacy in the field of pharmaceuticals. As a result, there is a tremendous increase in our understanding of the physicochemical properties, diagnostic and drug delivery aspects of CDs, which consequently has led us to design and develop CDs-based theranostic system for the treatment of multiple disorders. In this review, we aim to summarize the advances in application of CDs as nanocarrier including gene delivery, vaccine delivery and antiviral delivery, that has been carried out in the last 5 years.

Current perspectives on Vaxinia virus: an immuno-oncolytic vector in cancer therapy.

Viruses are being researched as cutting-edge therapeutic agents in cancer due to their selective oncolytic action against malignancies. Immuno-oncolytic viruses are a potential category of anticancer treatments because they have natural features that allow viruses to efficiently infect, replicate, and destroy cancer cells. Oncolytic viruses may be genetically modified; engineers can use them as a platform to develop additional therapy modalities that overcome the limitations of current treatment approaches. In recent years, researchers have made great strides in the understanding relationship between cancer and the immune system. An increasing corpus of research is functioning on the immunomodulatory functions of oncolytic virus (OVs). Several clinical studies are currently underway to determine the efficacy of these immuno-oncolytic viruses. These studies are exploring the design of these platforms to elicit the desired immune response and to supplement the available immunotherapeutic modalities to render immune-resistant malignancies amenable to treatment. This review will discuss current research and clinical developments on Vaxinia immuno-oncolytic virus.

Major complications following central neuraxial block - A multi-centre observational study in Maharashtra (MGMM CNB Study).

Background and Aims: Major complications of central neuraxial block (CNB) are rare and their incidence in India is not known. This information is essential for explaining risk and medico-legal concerns. The present multi-centre study in Maharashtra was conducted to provide insight into the characteristics of rare complications following this popular anaesthetic technique. Methods: Data were collected from 141 institutes to study the clinical profile of CNB. Incidence of complications like vertebral canal haematoma, abscess, meningitis, nerve injury, spinal cord ischaemia, fatal cardiovascular collapse, and drug errors was collected over one year. Complications were reviewed by audit committee to assess causation, severity, and outcome. 'Permanent' injury was defined as death or neurological symptoms persisting for more than six months. Results: Spinal anaesthesia (SA) was the most frequently used CNB in 88.76% patients. Bupivacaine and an adjuvant were used in 92.90% and 26.06% patients, respectively. Eight major complications (four neurological and four cardiac arrests) were reported in patients receiving SA. In seven of eight instances, SA was responsible or contributory for complication. The pessimistic incidence of complications (included cases where CNB was responsible; contribution was likely, unlikely and could not be commented) was 8.69/lakh and optimistic incidence (included cases where CNB was responsible or contribution was likely) was 7.61/lakh. 'Pessimistically' and 'optimistically' there were three deaths including one death due to quadriplegia following epidural haematoma after SA. Five out of eight patients recovered completely (62.5%). As only eight patients had complications of different types, it was difficult to establish statistical correlation of major complications with demographic or clinical parameters. Conclusion: This study was reassuring and suggested that the incidence of major complications following CNB was low in Maharashtra.

Genetic analyses of DNA repair pathway associated genes implicate new candidate cancer predisposing genes in ancestrally defined ovarian cancer cases.

Not all familial ovarian cancer (OC) cases are explained by pathogenic germline variants in known risk genes. A candidate gene approach involving DNA repair pathway genes was applied to identify rare recurring pathogenic variants in familial OC cases not associated with known OC risk genes from a population exhibiting genetic drift. Whole exome sequencing (WES) data of 15 OC cases from 13 families tested negative for pathogenic variants in known OC risk genes were investigated for candidate variants in 468 DNA repair pathway genes. Filtering and prioritization criteria were applied to WES data to select top candidates for further analyses. Candidates were genotyped in ancestry defined study groups of 214 familial and 998 sporadic OC or breast cancer (BC) cases and 1025 population-matched controls and screened for additional carriers in 605 population-matched OC cases. The candidate genes were also analyzed in WES data from 937 familial or sporadic OC cases of diverse ancestries. Top candidate variants in ERCC5, EXO1, FANCC, NEIL1 and NTHL1 were identified in 5/13 (39%) OC families. Collectively, candidate variants were identified in 7/435 (1.6%) sporadic OC cases and 1/566 (0.2%) sporadic BC cases versus 1/1025 (0.1%) controls. Additional carriers were identified in 6/605 (0.9%) OC cases. Tumour DNA from ERCC5, NEIL1 and NTHL1 variant carriers exhibited loss of the wild-type allele. Carriers of various candidate variants in these genes were identified in 31/937 (3.3%) OC cases of diverse ancestries versus 0-0.004% in cancer-free controls. The strategy of applying a candidate gene approach in a population exhibiting genetic drift identified new candidate OC predisposition variants in DNA repair pathway genes.

Molecular Genetic Characteristics of FANCI, a Proposed New Ovarian Cancer Predisposing Gene.

FANCI was recently identified as a new candidate ovarian cancer (OC)-predisposing gene from the genetic analysis of carriers of FANCI c.1813C>T; p.L605F in OC families. Here, we aimed to investigate the molecular genetic characteristics of FANCI, as they have not been described in the context of cancer. We first investigated the germline genetic landscape of two sisters with OC from the discovery FANCI c.1813C>T; p.L605F family (F1528) to re-affirm the plausibility of this candidate. As we did not find other conclusive candidates, we then performed a candidate gene approach to identify other candidate variants in genes involved in the FANCI protein interactome in OC families negative for pathogenic variants in BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, and FANCI, which identified four candidate variants. We then investigated FANCI in high-grade serous ovarian carcinoma (HGSC) from FANCI c.1813C>T carriers and found evidence of loss of the wild-type allele in tumour DNA from some of these cases. The somatic genetic landscape of OC tumours from FANCI c.1813C>T carriers was investigated for mutations in selected genes, copy number alterations, and mutational signatures, which determined that the profiles of tumours from carriers were characteristic of features exhibited by HGSC cases. As other OC-predisposing genes such as BRCA1 and BRCA2 are known to increase the risk of other cancers including breast cancer, we investigated the carrier frequency of germline FANCI c.1813C>T in various cancer types and found overall more carriers among cancer cases compared to cancer-free controls (p = 0.007). In these different tumour types, we also identified a spectrum of somatic variants in FANCI that were not restricted to any specific region within the gene. Collectively, these findings expand on the characteristics described for OC cases carrying FANCI c.1813C>T; p.L605F and suggest the possible involvement of FANCI in other cancer types at the germline and/or somatic level.