Case 312: Dercum Disease.

HISTORY: A 29-year-old woman was referred for US of bilateral breasts during evaluation for noncyclical mastalgia predominantly in the left breast of 8 months duration. She had been taking selective serotonin receptor inhibitors for the past 6 months for a clinical diagnosis of generalized anxiety disorder. A detailed medical history revealed breast cancer in the patient's mother and grandmother. There was no history of weight loss or appetite loss, nor was there a history of any altered bowel or bladder habits. The patient was overweight, with a body mass index of 26.8 kg/m2, and appeared anxious during the general physical examination, with an increased pulse (102 beats per minute) and normal blood pressure (118/82 mm Hg). Local examination revealed multiple small mobile painful lesions that were palpable in all quadrants of the bilateral breasts, anterior abdominal wall, and forearm. On further questioning, the patient reported similar painful lesions were present in her mother and one brother. Laboratory investigations showed a normal hemoglobin level (12.4 g/dL; normal range, 12-15 g/dL), a total leukocyte count of 9000 cells per microliter (9 cells × 109/L) (normal range, 4500-11 000 cells per microliter [4.5-11 cells × 109/L]), a normal differential leukocyte count (74% neutrophils [normal range, 40%-80%], 24% lymphocytes [normal range, 20%-40%], and 2% eosinophils [normal range, 1%-4%]), and an erythrocyte sedimentation rate of 5 mm per hour (normal range, 0-29 mm per hour). High-frequency US of bilateral breasts was performed in conjunction with Color Doppler US and shear-wave elastography of representative lesions in the breasts. Similar lesions were also found in the subcutaneous plane of the right forearm and the anterior abdominal wall.

Mammography and Digital Breast Tomosynthesis in Granulomatous and Nongranulomatous Mastitis.

INTRODUCTION: Digital Mammography (DM) is extensively used for breast imaging however, lesion visibility is often limited by overlapping tissues, which affects lesion characterization. Digital breast tomosynthesis (DBT) reduces the effect of overlapping tissues and helps in revealing obscured findings. We aimed to describe the mammographic findings in granulomatous and non-granulomatous mastitis and assess the utility of adjunctive DBT in lesion characterization. MATERIALS AND METHODS: DM and DBT images of histo-pathologically diagnosed cases of granulomatous (GM) and non-granulomatous mastitis (NGM) were reviewed according to the BI-RADS lexicon. Presence of contiguous/ interconnected lesions, tubular densities, interspersed hypodensities/fat densities within the involved areas were also assessed. The perceived utility of adjunct DBT was scored from 0-2. RESULTS: Of 33 reviewed patients (24 GM, 9 NGM; median age 39 years, range 24-78); 13/33 (39.4%) were under 35 years of age. DBT detected masses in 24/33 (72.7%), whereas only 15/33 (45.4%) were visible on DM alone. Contiguous or inter-connected lesions were found in 10/33 (30.3%) cases. Tubular extensions were seen in 14 cases and interspersed hypodensities in 15. None of the enlarged lymph nodes had irregular shape or indistinct margins or loss of fatty hilum. DBT was able to categorize more lesions as BIRADS 4a or below, as compared to DM alone. CONCLUSIONS: Mammographic presence of multiple contiguous iso-dense masses, reniform contour of axillary lymph nodes with preserved fatty hilum despite a large area of breast involvement favour a benign etiology; especially if DBT reveals tubular extensions or lesions with inhomogenous low density areas within.

Advanced molecular therapies for neurological diseases: focus on stroke, alzheimer's disease, and parkinson's disease.

Neurological diseases (NDs) are one of the leading causes of disability and the second leading cause of death globally. Among these stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) are the most common NDs. A rise in the absolute number of individuals affected with these diseases indicates that the current treatment strategies in management and prevention of these debilitating diseases are not effective sufficiently. Therefore, novel treatment strategies are being explored to cure these diseases by addressing the causative mechanisms at the molecular level. Advanced therapies like gene therapy (gene editing and gene silencing) and stem cell therapies aim to cure diseases by gene editing, gene silencing and tissue regeneration, respectively. Gene editing results in the deletion of the aberrant gene or insertion of the corrected gene which can be executed using the CRISPR/Cas gene editing tool a promising treatment strategy being explored for many other prevalent diseases. Gene silencing using siRNA silences the gene by inhibiting protein translation, thereby silencing its expression. Stem cell therapy aims to regenerate damaged cells or tissues because of their ability to divide into any type of cell in the human body. Among these approaches, gene editing and gene silencing have currently been applied in vitro and to animal models, while stem cell therapy has reached the clinical trial stage for the treatment of NDs. The current status of these strategies suggests a promising outcome in their clinical translation.

Case 312.

HISTORY: A 29-year-old woman was referred for US of bilateral breasts during evaluation for noncyclical mastalgia predominantly in the left breast of 8 months duration. She had been taking selective serotonin receptor inhibitors for the past 6 months for a clinical diagnosis of generalized anxiety disorder. A detailed medical history revealed breast cancer in the patient's mother and grandmother. There was no history of weight loss or appetite loss, nor was there a history of any altered bowel or bladder habits. The patient was overweight, with a body mass index of 26.8 kg/m2, and appeared anxious during the general physical examination, with an increased pulse (102 beats per minute) and normal blood pressure (118/82 mm Hg). Local examination revealed multiple small mobile painful lesions that were palpable in all quadrants of the bilateral breasts, anterior abdominal wall, and forearm. On further questioning, the patient reported similar painful lesions were present in her mother and one brother. Laboratory investigations showed a normal hemoglobin level (12.4 g/dL; normal range, 12-15 g/dL), a total leukocyte count of 9000 cells per microliter (9 cells × 109/L) (normal range, 4500-11 000 cells per microliter [4.5-11 cells × 109/L]), a normal differential leukocyte count (74% neutrophils [normal range, 40%-80%], 24% lymphocytes [normal range, 20%-40%], and 2% eosinophils [normal range, 1%-4%]), and an erythrocyte sedimentation rate of 5 mm per hour (normal range, 0-29 mm per hour). High-frequency US of bilateral breasts (Figs 1, 2) was performed in conjunction with Color Doppler US (Fig 3) and shear-wave elastography of representative lesions in the breasts (Fig 4). Similar lesions were also found in the subcutaneous plane of the right forearm (Fig 5) and the anterior abdominal wall (Fig 6).

Molecular Insights of Drug Resistance in Epilepsy: Multi-omics Unveil.

Epilepsy is a devastating neurological disorder mainly associated with impaired synchronic discharge that leads to sensory, motor, and psychomotor impairments. Till now, about 30 anti-seizure medications (ASMs) have been approved for the management of epilepsy, yet one-third of individuals still have uncontrollable epilepsy and develop resistance. Drug resistance epilepsy (DRE) is defined as the condition where two ASMs fail to control the seizure in epileptic patients. The leading cause of the resistance was the extended use of ASMs. According to various studies, alterations in some genes and their expressions, along with specific metabolic impairments, are suggested to be associated with ASMs resistance and DRE pathophysiology. Several factors aid in the pathophysiology of DRE, such as alterations in protein-encoding genes such as neurotransmitter receptors, drug transporters, ion channels, and drug targets. Furthermore, the altered metabolite levels of metabolites implicated in neurotransmitter signaling, energetic pathways, oxidative stress, and neuroinflammatory signaling differentiate the epileptic patient from the DRE patient. Various DRE biomarkers can be identified using the "integrated omics approach," which includes the study of genomics, transcriptomics, and metabolomics. The current review has been compiled to understand the pathophysiological mechanisms of DRE by focusing on genomics, transcriptomics, and metabolomics. An effort has also been made to identify the therapeutic targets based on identifying significant markers by a multi-omics approach. This has the potential to develop novel therapeutic interventions in the future.

Racemose neurocysticercosis: a case series.

Neurocysticercosis (NCC) is a common parasitic condition of the central nervous system in certain parts of the world. The racemose variety of NCC is distinct from the commonly seen parenchymal form. It frequently infiltrates the basal cisterns and Sylvian fissures. Imaging plays a vital role in the diagnosis; however, as their signal intensity is similar to cerebrospinal fluid and due to the absence of enhancement in most cases, imaging diagnosis is often difficult on the conventional MRI sequences. Here, we present five cases of racemose NCC to emphasize the importance of a heavily T2-weighted sequence (Fast Imaging Employing Steady-state Acquisition) sequence in the diagnosing this entity.

Translation and Validation of ID-Migraine Questionnaire to North-Indian Vernacular Languages.

Background: ID-Migraine is an established screening tool for migraine. Translation and validation in more languages can increase its reach and scope. Aim: To translate and validate ID-Migraine for screening migraine patients in two North-Indian vernacular languages, that is, Hindi and Punjabi. Methods: ID Migraine was translated into Hindi and Punjabi. Subjects with headaches in outpatient clinics were administered the questionnaire according to their preferred language of choice and referenced clinical evaluations, performed by an experienced neurologist, based on current the ICHD-3 diagnostic criteria. Results: One hundred subjects with complaints of headaches and 60 healthy controls were recruited after informed consent. Of the 100 subjects with headaches, 73 (73%) screened positive with a translated version of ID-Migraine, and 60 (60%) were eventually diagnosed with migraine without aura. The sensitivity of the Hindi version of ID-Migraine was 94% (95% confidence intervals, 79% to 99%); specificity, 56% (95% CI, 31% to 78%); positive predictive value, 79% (95% CI, 69% to 86%) and negative predictive value, 83% (95% CI, 55% to 95%). The Punjabi version demonstrated a sensitivity of 86% (95% CI, 68% to 96%); specificity, 43% (95% CI, 23% to 66%); PPV, 68% (95% CI, 58% to 76%); and NPV, 69% (95% CI, 44% to 86%). Conclusion: The translated versions of ID-Migraine demonstrated high sensitivity and fair specificity for screening migraine in Indian subjects who speak and understand Hindi and Punjabi.

Role of Omics in Migraine Research and Management: A Narrative Review.

Migraine is a neurological disorder defined by episodic attacks of chronic pain associated with nausea, photophobia, and phonophobia. It is known to be a complex disease with several environmental and genetic factors contributing to its susceptibility. Risk factors for migraine include head or neck injury (Arnold, Cephalalgia 38(1):1-211, 2018). Stress and high temperature are known to trigger migraine, while sleep disorders and anxiety are considered to be the comorbid conditions with migraine. Studies have reported various biomarkers, including genetic variants, proteins, and metabolites implicated in migraine's pathophysiology. Using the "omics" approach, which deals with genetics, transcriptomics, proteomics, and metabolomics, more specific biomarkers for various migraine can be identified. On account of its multifactorial nature, migraine is an ideal study model focusing on integrated omics approaches, including genomics, transcriptomics, proteomics, and metabolomics. The current review has been compiled with an aim to focus on the genomic alterations especially involved in the regulation of glutamatergic neurotransmission, cortical excitability, ion channels, solute carrier proteins, or receptors; their expression in migraine patients and also specific proteins and metabolites, including some inflammatory biomarkers that might represent the migraine phenotype at the molecular level. The systems biology approach holds the promise to understand the pathophysiology of the disease at length and also to identify the specific therapeutic targets for novel interventions.

Potential environmental toxicant exposure, metabolizing gene variants and risk of PCOS-A systematic review.

Exposure of environmental toxicants such as potentially toxic metals and pesticides have largely been attributed to produce adverse effects on general women's health and to be more precise on the reproductive system. In order to explore exposure of toxicants and metabolizing gene variants as risk factor for polycystic ovarian syndrome (PCOS), literature search was carried out using the databases PubMed, Central Cochrane Library, Google Scholar, Science Direct with appropriate keywords upto 6 December 2020. While most of the studies indicate higher serum Cu concentration and lower concentration of Mn as risk factor, studies also report presence of higher pesticide concentration in PCOS women. Genes such as MTHFR, CYPs participate in the metabolism of toxicants and may show different response due to underlying genetic variants. Thus, toxicant exposure are to some extent responsible for the pathogenesis of syndrome through oxidative stress and endocrine disruption, but the susceptibility may vary due to the underlying genetic polymorphism of the exposed population.