If you wish to free yourself from all the extra pounds that have been weighting you down for way too long, start using the BetterMe app and overhaul your entire life! They target the muscles in the core, glutes, hamstrings, and lats. This workout is best done with weights – either dumbbells or a barbell. The biosynthesis of oleanolic acid in plants begins with the cyclization of 2,3-oxidosqualene, a precursor produced in the mevalonate pathway, which highlights the affiliation of this triterpene to a broad family of terpenoid natural products, including sterols and triterpenoid saponins . These differences manifest at the level of affinity for enzymes, receptors, and transporter proteins, which consequently influences different bioavailability and toxicity profiles, providing a basis for the rational design of new compounds with targeted pharmacological action . An isomer of oleanolic acid, ursolic acid, has a similar structure but differs in the spatial arrangement of the methyl group at the C-20, which contributes to subtle differences in their biological activity and interactions with molecular targets. Furthermore, the lipophilic nature of oleanolic acid, resulting from the predominance of hydrocarbon segments in its structure, determines its low water solubility, which poses a challenge in pharmaceutical formulations but also facilitates interactions with cell lipid membranes. The stereochemistry of oleanolic acid is strictly defined (Figure 6), which influences its interactions with biological receptors and enzymes, and any changes in its spatial configuration can significantly modify its activity . GeneReviews’ webpage on “RFC1 CANVAS / spectrum disorder” (Cortese et al, 2020) stated that the diagnosis of RFC1 CANVAS / spectrum disorder is established in a proband with suggestive findings and bi-allelic intronic AAGGG pentanucleotide expansions in RFC1 identified by molecular genetic testing that is targeted to detect these expansions. Of the 12 genes listed under the UroSeq Genetic Panel for prostate cancer, all but 2 (EPCAM and HOXB13) are listed under National Comprehensive Cancer Network’s Biomarkers Compendium (2020) menu of “Prostate cancer” (Category 2A). The UroSeq Hereditary Gene Panel is used for diagnosis, prognosis, recurrence/risk assessment, as well as therapeutic management of patients with prostate cancer. Furthermore, an UpToDate review on “Overview of cerebellar ataxia in adults” (Todd and Shakkottai, 2024) states that “Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) – CANVAS is an adult-onset disorder characterized by the association of bilateral vestibulopathy with cerebellar ataxia and sensory neuronopathy. The authors stated that pathogenic AAGGG repeat expansions in RFC1 cannot be detected by sequence-based multi-gene panels or exome sequencing; however, they can be suspected based on genome sequencing. The purpose of such testing is to help rule out secondary or psychogenic causes of dystonia, and for family planning purposes. ACMG underscores that expanding the number of conditions screened increases the likelihood of identifying carriers, but also introduces challenges in variant interpretation and clinical validity, especially for rarer conditions (Gregg et al., 2021). Talk about a keto transformation, right?? Are you skeptical that you can ever achieve an actual keto transformation? Are you dreaming of a keto transformation for yourself? Bansal stated that the low energy levels and brain fog that you experience during the first week, often improve during the second week. "When evaluating whether this diet is good for you, consider your lifestyle, preferences, and long-term goals," she advised. For further motivation, a study revealed that people who exercised five days a week for just 30 mins saved on average, $3500 a year in medical expenses on heart-related issues alone. And studies have shown that exercise regimes have a 50% dropout rate in the first six months. I am notorious for being constantly tired (Shirley definitely agrees) and often using caffeine for energy. Improved energy and focus. This became a common occurrence, and our members have probably seen me pretty much every weekday! Luhmann et al (2021) noted that acute lymphoblastic leukemia (ALL) is the most prevalent type of cancer occurring in children; it is characterized by structural and numeric genomic aberrations that strongly correlate with prognosis and clinical outcome. The authors concluded that these findings highlighted the potential for OGM to provide a cost-effective and easy-to-use alternative that would allow comprehensive detection of chromosomal aberrations and SVs, which could give rise to an era of "next-generation cytogenetics". It enables a timely and cost-effective analysis allowing identification of complex cytogenetic events, including those currently inaccessible to standard techniques. The authors concluded that the findings of this study indicated that the solid tissue DNA extraction protocol, OGM and SV analysis could be applied to a wide variety of solid tumors to capture SVs across the entire genome with functional importance in cancer prognosis and treatment. Goldrich et al (2021) noted that genomic structural variants comprise a significant fraction of somatic mutations driving cancer onset and progression; however, such variants are not readily revealed by standard NGS. Month 1 on the ketogenic diet was definitely an adjustment period. Month 1 on the ketogenic diet was a rollercoaster of emotions. Get ready to be inspired, motivated, and maybe even convinced to give the ketogenic diet a try yourself! Not only did I lose weight, but my energy levels skyrocketed, and my skin cleared up. This is if you want to continually challenge your muscles by increasing the weight, reps, or sets you’re doing. If you’re looking to lose fat, doing more cardio is generally the way to go. In fact, research shows that shorter, more intense workouts are more effective for fat loss than longer, moderate-intensity workouts (2). How Much Weight Can You Lose In A Month On Keto With Intermittent Fasting? However, increasing the portion of protein in KD may be a practical approach for preserving muscle mass following the BM loss phase. Although it is reported that carbohydrate consumption may not significantly affect MPS(255,256), some previous studies have shown its beneficial effects on net muscle protein balance by reducing MPB(257,258). Positive effects of carbohydrate intake on net muscle protein balance could be another possible mechanism of higher FFM loss in KD. Although these results should be interpreted with caution given the low number of participants, this study strongly suggests that KD promote FM loss while preserving muscle mass compared with LCD. Although KD’ sex-specific mechanisms of action are unclear, higher basal energy expenditure because of higher FFM in men may be the main cause of these differences(279). For example, Lyngstad et al. compared body composition changes following 13 weeks of KD in men and women. Females are also likely to lose less BM than males during a dietary intervention(273), although they are more likely to adopt and adhere to a diet initially(274). Further research is needed to determine whether the effect of KD in individuals following this dietary approach. It seems that the short-term adverse effects of KD on FFM are because of body water reduction. C9orf72 genetic testing - no specific code: Through exploring these questions, the study offers novel insights into this significant stream of Buddhist philosophical thought, and is a contribution to larger discussions on relativism within world philosophy. This study offers the first comprehensive investigation of its historical development across Buddhist traditions. While previous studies showed that mechanical stretch increased alveolar epithelial cell necrosis and apoptosis, the impact of cell death during repair was not determined. ColoNext™ (Ambry Genetics) utilizes next generation sequencing to offer a comprehensive testing panel for hereditary colon cancer and targets detection of mutations in 14 genes (APC, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, and TP53) (Raman, et al., 2013). The report concluded that, until such benefit can be demonstrated, the routine genetic testing of patients with complex eye diseases, or unaffected patients with a family history of such diseases, is not warranted. Thus, the author recommends genetic testing in patients with "clinical presentation or pedigree that is suggestive for CPVT", in which a genetic screening panel may help support the diagnosis. The authors state that mutations in other genes such as KCNJ2, Ank2, TRDN and CALM1 have been identified in patients with clinical features similar to CPVT; however, it is not clear whether they are phenocopies of CPVT. Although the diagnostic yield from genetic testing is less than that for the LQTS (about 50 %) in patients with typical clinical features, a positive genetic test may be of value for the individual patient (given the prognostic implications) and for screening family members (given the difficulties in clinical screening methods) (HRUK, 2008). In another study, Paoli et al. reported that KD may be used with the caution during body building preparation because it can blunt hypertrophic responses(346). An increased rate of glycolysis and lactate production during exercise also hinders fat oxidation by reducing the entry of long-chain fatty acids into the mitochondria(343). In addition, results from a study by Wood et al. indicated that a KD without exercise led to less FFM loss than an LFD and similar losses compared with an LFD combined with RT(339). Indeed, this hypothesis is supported by several human studies that have reported that chronic KD result in attenuated muscle mass. The authors presented a general overview of the global management of patients with MBD, this conceptual framework will be adopted and validated in the evidence-based, disease-specific guidelines under development by the IWG. An UpToDate review on “Approach to the adult with a suspected bleeding disorder” (Ma, 2021) states that “Genetic testing for known platelet function disorders (e.g., using a gene panel) is becoming more widely available and may be reasonable in certain individuals with a suspected platelet disorder of genetic origin”. It can be used when patient’s history suggests multiple coagulation disorders, or for identification of carriers with family history of unspecified bleeding disorders to provide accurate reproductive risk assessment and genetic counseling. How One Woman Turned Her Battle With Eczema Into a Lifeline for Others X-linked intellectual disability (XLID) is a genetically heterogeneous disorder with more than 100 genes known to date (Tzchach et al, 2015).Carrier testing may be offered to couples considering pregnancy, including those with a family history of SMA, and prenatal diagnosis should be made available to all identified carriers.Podcasts about keto, fitness, and nutrition is motivating to me to learn about my body while I’m actively working it.The study posits that the poetic expressiveness found in archaic philosophies of both India and Greece provides a valid medium for engaging in philosophical discourse.In this patient group, carbohydrate intake is generally around 15–20 g/day and the rates of seizure reduction and adherence are lower compared to those of the child population (Kossoff et al., 2008; Zare et al., 2017; Payne et al., 2018).Cases with detailed clinical information were highlighted to describe various utility scenarios for episignature testing.The test is intended to determine if a woman has an increase chance of developing breast, ovarian, and/or uterus cancer. For many women, losing belly fat is a top priority when it comes to body transformation. By following a calorie-controlled diet paired with regular physical activity, women can experience significant weight reduction (2). It’s important to find a balance that works for you and your body, rather than following strict diets or extreme workout plans. My experiment was a great example of something I say to my patients every single day — there is no “one size fits all” diet out there. As for fat, I still see a huge benefit in maintaining healthy fats in the diet. However, most studies show that KD have no positive effect on preserving FFM than an LFD(29).The most useful approach to diagnosis is obtaining a history and physical examination, followed by non-invasive tests and invasive studies if needed.You won’t believe the stories of ordinary people who achieved extraordinary results by adopting this popular low-carb, high-fat eating plan.So much better than the grotesque ungraceful bodybuildersHHT may be diagnosed clinically (using three or more Curaçao Criteria or by documentation of a pathogenic or likely pathogenic variant in an HHT gene. International consensus diagnostic criteria (the Curacao diagnostic criteria) are based upon four findings.Healthy eating is a prerequisite for transformation with weightlifting.The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics.Laurent-Puig et al (2009) stated that the occurrence of KRAS mutation is predictive of non-response and shorter survival in patients treated by anti-epidermal growth factor receptor (anti-EGFR) antibody for metastatic colorectal cancer (mCRC), leading the European Medicine Agency to limit its use to patients with wild-type KRAS tumors.Clinicians need to be aware that a child can have CF despite a normal sweat test following NBS, and if symptoms suggest the diagnosis, further testing, including extended genome sequencing, is needed. I soon realized why every keto book I read had multiple uses and recipes for coconut oil, egg yolks, and bacon. A quick check of my urine using my ketone at-home stick kit revealed I was on my way down the ketosis highway and I was euphoric. During this time, I was tired, had crazy sugar cravings and was generally mean to my poor husband. I did find a few no-added-sugar coconut bars I liked, but in general, it was best to skip any after-dinner eats. Some medical experts assume that carbohydrate restriction causes more purines from nucleic acids to break down to uric acid, either due to increased death of cells or from a higher dietary protein intake (i.e., meat containing nucleic acids). Long ago, we noted that even when dietary carbohydrate is very low, muscle glycogen only drops to about half of its prior level after 4-6 weeks on a high fat diet (Phinney, 1980; Phinney, 1983). ’ Yes, we know that a lot of disease symptoms and health indicators get much better soon after someone starts on a ketogenic diet. She maintained her 80-pound weight loss for over 5 years through consistent fat-adapted metabolism changes. Nanoliposomes are frequently employed in targeted drug delivery, especially for anticancer agents or drugs with poor aqueous solubility .In many instances, reliable mutation analysis requires accurate determination of specific allelic variations in a proband (affected individual in a family) before subsequent carrier testing in other at-risk family members can be accurately performed.Although an increasing number of genes have been identified to have independent effects on BMD, few studies have been performed to identify genes that interact with one another to affect BMD.Kim et al (2013) noted that BMD loci were reported in Caucasian genome-wide association studies (GWAS).This ongoing work has identified 22 genes with mutations that are deemed to be significant, as judged by their presence in multiple tumors and their likely disruptive effects on gene function.Furthermore, ROS can influence epigenetic processes—oxidative modifications of nitrogenous bases may lead to abnormal DNA methylation, while histone protein damage alters chromatin structure and gene accessibility to transcription factors.Powell continues to share her weight loss journey to her 256k followers on Instagram.Suzanne Ryan began her keto journey way back in 2015. It should be mentioned that higher BM decrements can result in higher FFM loss, and therefore, higher FFM loss may be the result of more BM loss during KD. However, it should be noted that equivocal reports suggested that KD do not affect muscle mass(253,336,337). Furthermore, it has been reported that the KD inhibits the mTOR signalling pathway by reducing the expression of Ribosomal protein S6 kinase beta-1 and Akt(225). Later, in this paper, we will enlarge on body composition changes in RT and endurance training (ET) athletes adhered to KD. The low bioavailability of triterpenes, including oleanolic acid, is a well-documented problem resulting from their intensive first-pass metabolism in the liver, which requires the use of advanced chemical modifications or appropriate carriers. Furthermore, the complexity of oleanolic acid’s mechanisms of action, which involve modulation of multiple signaling pathways, requires further in-depth research to fully understand its therapeutic potential and optimize treatment protocols. This selective redox modulation underlies OA’s potential as a chemopreventive and adjuvant anticancer agent, offering cytoprotection to normal tissues while targeting malignant cells. In normal cells, OA reinforces antioxidant defenses, restores redox balance, and supports survival, whereas in cancer cells it pushes ROS levels beyond the threshold of tolerance, inducing oxidative stress-mediated apoptosis. These investigators stated that although genetic testing may provide high-yield results in the appropriate clinical setting, widespread genetic testing is not yet justified for all patients with pulmonary fibrosis because the relevance of such results remains unclear in many settings. They noted that these findings suggested the need for evidence-based and consensus guidelines as to the most appropriate utilization of diagnostic and pre-symptomatic genetic testing in routine clinical management of patients with ALS and their extended families.On behalf of the Pulmonary Fibrosis Foundation Genetic Testing Work Group, Newton et al (2022) examined the role of genetic testing in pulmonary fibrosis. These investigators stated that these data suggested that the clinical application of genetic testing in symptomatic patients is not always evidence-based, and that genetic counseling of patients and their families does not occur routinely as a standard of care in all instances. Up to half of patients have motor system involvement with upper and/or lower motor neuron signs or, less commonly, parkinsonism. Clinical features of CANVAS include gait imbalance in all, and variable presence of dysesthesia, oscillopsia, impaired vibratory sensation, and loss of ankle reflexes. In rare patients with a typical CANVAS phenotype and only monoallelic repeat expansion of RFC1, sequencing has identified truncating pathogenic variants in the coding region of the other RFC1 allele. Most familial and sporadic forms are caused by homozygous AAGGG repeat expansion within intron 2 of the RFC1 gene, which encodes a large subunit of replication factor C and is involved in DNA synthesis and repair. A total of 15 individuals diagnosed with CANVAS and carrying only 1 heterozygous (AAGGG)n expansion in RFC1 underwent whole-genome sequencing or WES to test for the presence of a 2nd variant in RFC1 or other unrelated gene. Moreover, the availability of more subjects in future may facilitate the establishment of an episignature that can be utilized for diagnosis in a clinical setting and for reclassification of variants of unknown clinical significance”. Sadikovic and colleagues (2021) described the clinical implementation of genome-wide DNA methylation analysis in rare Mendelian disorders across the EpiSign diagnostic laboratory network and the assessment of results and clinical impact in the first subjects tested. In some cases follow-up testing may be suggested to further characterize the underlying genomic abnormality and to confirm or rule out a diagnosis. The EpiSign Variant is a targeted review of the methylation data based on a strong clinical suspicion and/or a previously identified variant of uncertain significance (VUS). Abnormalities detected using this initial screen may require additional targeted testing to confirm and further characterize the underlying genomic abnormality. In the presence of arrhythmic syncope or cardiac arrest, the panel agrees that a QTc ≥460 ms is sufficient to consider a diagnosis of LQTS (Zeppenfeld et al., 2022).Wappler (2010) stated that malignant hyperthermia (MH)-susceptible patients have an increased risk during anesthesia. Genetic screening identifies a mutation in 75% of LQTS cases and three main genes account for 90% of positively genotyped cases. The authors state that undisputed genes that are known to cause LQT1, LQT2 and LQTS3 include KCNQ1, KCNH2 and SCN5A, respectively, with gene-specific triggers being exercise (LQTS1), emotional stress (LQTS2) and sleep (LQTS3). The specific genetic tests one would need would depend on which clotting factors are deficient, rather than testing for all coagulation disorders. Furthermore, an UpToDate review on “Approach to the child with bleeding symptoms” O’Brien, 2021) does not mention genetic testing as a diagnostic tool. However, genetic testing is not listed in the “Summary and Recommendations” section of this UTD review. Moreover, aggregometry and genetic testing should be ordered by a hematologist or other hemostasis expert. OncoVue is based on an un-published case-controlled associative study that examined common genetic polymorphisms and medical history variables.Overall, the ketogenic diet has changed my life for the better.The authors note that "no large randomized, placebo-controlled studies meeting usual criteria for highest levels of evidence are available in the genetic cardiomyopathy literature".Never skip rest days as they allow your muscles to recover and grow and prevent overtraining.Mom was at her high school weight of 115 lbs.At first I was doing low carb, high fat vegan meals, then I went down the rabbit trail of the vegan ketogenic diet.The investigators found that, while the genetic score did help predict who would develop diabetes, once other known risk factors were taken into consideration, it offered little additional predictive power.Physical activity has been well-documented to have positive effects on mood and energy levels. Furthermore, the Endocrine Society's clinical practice guideline on congenital adrenal hyperplasia (Speiser et al, 2010) suggested genotyping only when results of the adrenocortical profile following cosyntropin stimulation test are equivocal or for purposes of genetic counseling. Nonetheless, the authors concluded that the clinical DNA methylation testing including episignatures, imprinting, and promoter analysis provided by an integrated network of clinical laboratories enables test standardization and demonstrates significant diagnostic yield and clinical utility beyond DNA sequence analysis in rare diseases. The authors concluded that the robust and specific CTCF/IDD21 episignature expands the growing list of neurodevelopmental disorders with distinct DNA methylation profiles, which can be applied as supporting evidence in variant classification.Kerkhof and colleagues (2024) aimed to assess the diagnostic utility and provide reporting recommendations for clinical DNA methylation episignature testing based on the cohort of patients tested through the EpiSign Clinical Testing Network. It was amazing to see the progress I had made, and I was so proud of myself for sticking to the diet.This article explores the issues of phenomenon and genesis in Early Buddhist thought through a comparative analysis with the Eleatic tradition, aiming to enrich the understanding and dialogue between these philosophical and religious traditions.The concentrations of several hormones and nutrients influence appetite and are altered after BM loss induced by a KD(119,120).Three months of gym work usually results in improved muscle definition, increased strength, and better cardiovascular fitness.Mattioni et al (2013) noted that TP53 gene mutations can lead to the expression of a dysfunctional protein that in turn may enable genetically unstable cells to survive and change into malignant cells.Recessive mutations in ABCA3 were first attributed to fatal respiratory failure in full-term neonates, but they are also increasingly being recognized as a cause of respiratory disorders with less severe phenotypes in older children and also adults.The hardest part my 6 month body transformation was keeping a positive outlook on those weeks that “something” came up. The exome sequencing platform used provided 30× or more coverage for all of the exons on the commercial targeted gene panels, supporting our assumption of 100% analytical sensitivity for exome sequencing. The largest nonimmune hydrops fetalis targeted gene panel would have had a diagnostic yield of 18% compared with 29% with exome sequencing. The authors identified 7 laboratories that offer 10 relevant targeted gene panels; 6 are described as RASopathy panels, 3 as nonimmune hydrops fetalis panels, and 1 as a metabolic panel. This was a secondary analysis of a cohort study of exome sequencing for nonimmune hydrops fetalis, in which recruitment, exome sequencing, and phenotype-driven variant analysis were completed in 127 pregnancies with features of nonimmune hydrops fetalis. In these patients, the incidence of false positive and false negative results and their implications for management remain unknown. Voltage-gated sodium channels are transmembrane proteins that produce the ionic current responsible for the rising phase of the cardiac action potential and play an important role in the initiation, propagation, and maintenance of normal cardiac rhythm. Per GeneReviews (Legius and Stevenson, 2020), Legius syndrome, also known as neurofibromatosis type 1-like syndrome, is characterized by multiple café au lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1 (NF1). Genetic testing is not recommended when the LVNC phenotype is identified by chance in asymptomatic individuals with otherwise normal cardiovascular structure and function. To maximize muscle hypertrophy through the KD, daily total energy intake needs to be optimized. Wilson et al. compared the KD and a conventional diet over 11 weeks and found that both groups showed similar levels of muscle hypertrophy and increased strength. This utilization could also be attributed to sodium and water excretion and body water loss due to glycogen depletion . Several studies have suggested that carbohydrate restriction in the KD may contribute to reduced muscle mass. Based solely on these findings, it can be concluded that the KD may be more effective for reducing visceral fat than HIIT alone without dietary intervention. The remaining 732 referrals underwent targeted episignature analysis for assessment of sequence or copy-number variants (CNVs) of uncertain significance or for assessment of clinical diagnoses without confirmed molecular findings, and 32.4% (237/732) were positive. An international working group, representing distinct EpiSign Clinical Testing Network health jurisdictions, collaborated to establish recommendations for interpretation and reporting of episignature testing. The authors outlined the logistics and data flow between an integrated network of clinical diagnostics laboratories in Europe, the United States, and Canada. Because some individuals do not have symptoms, determining the true frequency of these disorders in the general population is difficult. Due to the complexity of tumors and high level of noise and biases in WES data, employing advanced novel segmentation, normalization and de-noising techniques that are designed specifically for cancer data is needed. After losing some serious weight on keto, Katelyn Falcone stresses to her Instagram followers not to focus as much on numbers on a scale; instead, count victories like feeling confident in your own skin. This mom of two lost over 80 pounds on the keto diet and shares daily meals and inspiration on Instagram. Even if you’re not thinking of adopting the keto diet to drop excess pounds, these stories will provide the inspiration you need to put down the pint of ice cream and whip your diet into shape. If you need some motivation to try a new diet, check out these incredible keto transformations. But, noticeable fat loss usually takes around 4 months or more. SBMA is caused by a mutation in the AR (androgen receptor) gene which encodes androgen receptor on the X chromosome. This testing is suggested for infants presenting with acute respiratory failure in the absence of other explanations, or in older children with chronic presentation or family history of ILD, especially if the diagnostic imaging is consistent with ILD ”. The most useful approach to diagnosis is obtaining a history and physical examination, followed by non-invasive tests and invasive studies if needed. Overall, available experimental and preclinical data indicate that oleanolic acid, through pleiotropic modulation of oxidative stress and signaling networks, holds promise as an adjuvant agent in cancer prevention and therapy. Not only will you save money, you’ll also be at lower risk of developing many chronic diseases including type 2 diabetes, dementia, arthritis and many types of cancer. After listening to this podcast, you’ll understand why the keto diet is so perfect for women over 40 with hormonal imbalance who are experiencing problems losing weight. "You may notice a decrease in body fat and an increase in lean muscle mass," she concluded. After a month of following a ketogenic diet, you may notice changes in your body composition. To address this, numerous derivatives and conjugates are being synthesized, demonstrating enhanced biological activity and improved pharmacokinetic properties, which are crucial for their potential clinical application . To optimize the bioavailability and therapeutic efficacy of oleanolic acid, intensive research is underway on its chemical modifications and the development of innovative delivery systems. OA limits the proliferation, migration, and self-renewal capacity of cancer cells, reduces the expression of stemness and EMT markers, and increases sensitivity to chemotherapeutic agents. These results indicate that OA induces breast cancer cell death primarily through cytotoxic autophagy dependent on the inhibition of the PI3K/AKT/mTOR pathway . OA inhibited the phosphorylation of AKT and mTOR kinases, key regulators of cancer cell survival, growth, and metabolism, thereby promoting autophagy activation. In summary, CDDO-Me remains a milestone compound in triterpenoid chemistry, serving as a prototype for designing multifunctional oleanane derivatives with improved anticancer, anti-inflammatory, and antioxidant properties. The modulation of these pathways links CDDO-Me’s anticancer efficacy with its anti-inflammatory and cytoprotective potential, making it a unique dual-function compound. Its mechanism of action extends beyond direct tumor cytotoxicity—it also involves anti-inflammatory and antioxidant effects, suppression of ROS generation, and modulation of gene expression through redox-sensitive transcription factors. Remarkably, CDDO-Me was effective at low micromolar and submicromolar concentrations, which underscores its potency compared to the parent oleanolic acid. Rather, perhaps other aspects of the body’s energy regulation and homeostasis are undergoing similar slow changes as well with the net effect resulting in the process we long ago named ‘keto-adaptation’ (Phinney, 1980; 1983).This complex mechanism involves the induction of the transcription factor Nrf2, which regulates the expression of genes encoding antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase.It is also used for carrier screening of potential parents to identify genetic mutations for which they are at risk of passing along to their children.Hanson et al (2001) reported that homozygosity for the C282Y mutation has been found in 52 to 100 % of previous studies on clinically diagnosed index cases.A quick check of my urine using my ketone at-home stick kit revealed I was on my way down the ketosis highway and I was euphoric.Unverricht-Lundborg disease (EPM1) is an inherited neurodegenerative disorder characterized by stimulus-sensitive myoclonus, and tonic-clonic epileptic seizures, which has typical onset from 6 to 15 years of age and worsens over time.It has been discussed that the interaction of both mutations could be responsible for both the unexpected severity of ATS symptoms and the very early onset of inner ear deafness in the girl.An UpToDate review on “Congenital and acquired disorders of platelet function” (Coutre, 2013) states that “Giant platelet disorders – Inherited platelet disorders with giant platelets are quite rare (picture 2 and algorithm 1 and table 4). Intermittent fasting can speed up ketosis when combined with your low-carb living approach. Weight loss journey stories show that personal goals work better than copying someone else's plan. Ketogenic lifestyle success depends on your body's unique response to carbohydrate restriction. Realistic goals make all the difference when starting your keto journey. Sustained energy lasted throughout my day without crashes. Hour Eating Window This Washington state mom lost 114 pounds after starting the keto diet back in 2016. After being on the diet for six months, this Aussie lost some serious weight and has never felt better. She keeps her 153k followers updated on her continuing weight loss journey on Instagram. Campo et al (2014) noted that ILD occurring in children is a condition characterized by high frequency of cases due to genetic aberrations of pulmonary surfactant homeostasis, that are also believed to be responsible of a fraction of familial pulmonary fibrosis. Devine and Garcia (2012) stated that the interstitial lung diseases (ILDs), or diffuse parenchymal lung diseases, are a heterogeneous collection of more than 100 different pulmonary disorders that affect the tissue and spaces surrounding the alveoli. In contrast, other studies (de Visser 2000; Luddington et al, 2000; Dindagur et al, 2006) found no significant increase in thrombotic risk (GeneTests, University of Washington, Seattle, 2007). Shephard and Semsarian (2009) stated that genetic heart disorders are an important cause of SCD in the young. If you are wondering if the keto diet works, this show is going to be a huge help for you. You can often find Ishaan lifting weights or trying healthy food and sipping protein shakes, but he will wolf down a plate of pesto pasta with equal gusto. It's important to listen to your body's hunger and fullness cues and ensure you're consuming a well-balanced diet. As you enter the second week, your body starts to adapt to the ketogenic state. In 2006, Bossler and group describe the results of mutation analysis on a consecutive series of 200 individuals undergoing clinical genetic testing for HHT. Genetic testing involves sequence and duplication/deletion analysis and identifies a mutation in roughly 80% of patients with clinical disease. The authors recommend "genetic tests for FRDA, SCA 1, 2, 3, 6,7 (12, 17) and FXTAS" in adults; however, "genetic testing of asymptomatic ‘at-risk’ minors is not generally recommended, but should be considered on a case-by-case basis". The etiology of non-syndromic unilateral sensorineural hearing loss is usually environmental and not genetic, with genetic testing diagnostic yields of 1-5% (Kocharyan et al, 2023; Smith et al, 2024) Approximately 50% of nonsyndromic hearing loss can be attributed to a genetic cause, and may be inherited in an autosomal recessive (70% of patients), autosomal dominant (20% of patients), with mitochondrial, X-linked and other genetic causes making up the remainder of patients. Finally, I read about the bad breath often accompanied with ketosis. I realized success in sticking to this diet would always be made easier the more control I had of my environment. On a business trip, I found myself at an event with a plated dinner that I could not eat due to its mound of quinoa sitting under a protein source I was allergic to. I also had a nasty bout of constipation as my body transitioned away from the whole grain and bean-based fiber that kept me regular. Ardissino and co-workers (2021) noted that aHUS is mainly due to complement regulatory gene abnormalities with a dominant pattern but incomplete penetrance; therefore, healthy carriers can be identified in any family of aHUS patients, but it is unpredictable if they will eventually develop aHUS. These researchers hypothesized that the proband inherited from his mother a genetic abnormality in a complement circulating factor that has not been identified yet, which synergized with the CD46 RV in predisposing him to the aHUS phenotype. However, the absence of variants of a given set of genes does not preclude the diagnosis of aHUS”. Unverricht-Lundborg disease (EPM1) is an inherited neurodegenerative disorder characterized by stimulus-sensitive myoclonus, and tonic-clonic epileptic seizures, which has typical onset from 6 to 15 years of age and worsens over time. The timing depends on your goals, like improving cardio, building muscle, or losing weight, as well as your fitness level. Remember that weight loss can happen at different rates for each person. A good weight loss goal is 1–2 pounds per week, totaling around 16–32 pounds in four months. Results depend on your fitness level, workout effort, diet, and body type. Versiti Autosomal Dominant Thrombocytopenia Panel For association studies, allele counts were extracted and allelic association calculated whenever possible. However, many patients (up to 25 %) cannot tolerate or discontinue statin therapy due to statin-induced myopathy (SIM). Positive (+ve) immunostaining was found in 9 patients for p53 (47.37 %) and 8 patients for Ki67 (42.10 %). And without a healthy lifestyle in check, which includes things like sleep, reasonable sunshine, walking, etc., then your body won’t be in good enough shape to see results. Inside we’ll take a closer look at four women as they set goals, begin lifting weights and eating differently, and see their monthly progress updates. See how these women combined lifting weights, nutrition, and lifestyle changes to see amazing before-and-after transformations. I was initially shocked by how much my body had changed. Overall, Month 3 was a huge success for me on my ketogenic journey. It was a real revelation for me, and I felt proud of myself for sticking to the diet. Instead, I had a constant source of energy throughout the day. Another big change I noticed was in my energy levels. Polycystic Liver Disease SMN1 deletions are detected by polymerase chain reaction (PCR) amplification of exon 7 of the SMN genes, followed by restriction fragment length polymorphism (RFLP) analysis. However, inheritance patterns of sleep-walking are poorly understood and there have been no prior reports of genes or chromosomal localization of genes responsible for this disorder. Genetic diagnosis of BBS is complicated due to lack of gene-specific disease symptoms, but is gradually becoming more accessible with the invention of multigene sequencing technologies. A minimum of 20 BBS genes have already been identified, and all of them are involved in primary cilia functioning. Combining the screen with exome sequencing data identified recessive mutations in PIBF1, also known as CEP90, and C21orf2, also known as LRRC76, as causes of the ciliopathies Joubert and Jeune syndromes. Nonsyndromic hearing loss is defined by the absence of malformations of the external ear or other medical problems in the affected individual. In order to test this hypothesis, these investigators performed co-immuno-precipitation and confocal microscopy analyses with human breast cancer MCF7 cells. These researchers previously found that ERα interacted with mitochondrial protein HADHB and affected the thiolytic cleavage activity of HADHB in β-oxidation. These investigators had demonstrated that the expression of ERα affects HADHB activity, and a combination of 17β-estrodiol and tamoxifen affects the activity of HADHB prepared from human breast cancer cells that express ERα but not from the cells that are ERα deficient. In addition, these researchers have shown that ERα co-localized with HADHB in the mitochondria by confocal microscopy, and the 2 proteins interact with each other within mitochondria by performing co-immuno-precipitation using purified mitochondria as starting materials. NCCN guidelines and compendia for prostate cancer do not include a recommendation for HSD3B1 testing.GeneReviews’ webpage on “RFC1 CANVAS / spectrum disorder” (Cortese et al, 2020) stated that the diagnosis of RFC1 CANVAS / spectrum disorder is established in a proband with suggestive findings and bi-allelic intronic AAGGG pentanucleotide expansions in RFC1 identified by molecular genetic testing that is targeted to detect these expansions. The purpose of such testing is to help rule out secondary or psychogenic causes of dystonia, and for family planning purposes.The UroSeq Hereditary Gene Panel is used for diagnosis, prognosis, recurrence/risk assessment, as well as therapeutic management of patients with prostate cancer. To integrate OGM into the routine diagnostic workflow and on a larger scale, further validation and optimization of the workflow (e.g., increasing computing capacity and automated sample preparation to reduce processing time) is needed.OvaNext (Ambry Genetics) is a next generation (next-gen) sequencing panel that simultaneously analyses 19 genes that contribute to increased risk for breast, ovarian, and/or uterine cancers (Raman, et al., 2013). These researchers demonstrated that typical genetic alterations can be identified with high accuracy, while at the same time the unbiased assessment of the transcriptome also allows the identification of potentially new targets in patients, where these genetic aberrations are absent. Jiang and co-workers (2015) stated that whole transcriptome analysis plays an essential role in deciphering genome structure and function, identifying genetic networks underlying cellular, physiological, biochemical and biological systems and establishing molecular biomarkers that respond to diseases, pathogens and environmental challenges. The AAP has introduced an updated tiered agnostic approach that prioritizes diagnostic yield and practical considerations, allowing pediatricians to refer patients to a geneticist at any point in the diagnostic process, or to seek higher-level evaluations from neurologists or experienced developmental pediatricians if a geneticist is not available. The article emphasizes the necessity of comprehensive evaluations, including family history and clinical examination, and the involvement of geneticists in further assessments, especially for nonsyndromic GDD/ID cases. After maintaining a low-carb and basically no sugar diet for so long, overindulging can shock your body and leave you feeling sick, crampy, and withdrawn as you digest. That led to the quick weight loss I experienced in the first few weeks. I can say for sure that I’m passed the point of thinking of keto as a fad diet and more now consider it a lifestyle. Each person inherits different strengths and weaknesses from the gene pool, so it's important to take your time and found out what gym workout is best for your unique body. During the first month of following the ketogenic diet and considering your physical health, including side effects and physical problems, approximately how many days of that month were you not in a good health condition? Instead of worrying about my weight, I think more about inches I’m losing or gaining.Vegetable oils, particularly olive oil, contain oleanolic acid in the unsaponifiable fraction, which contributes to their health-promoting properties and is an important element of the Mediterranean diet, known for its beneficial effects on health.This 25-year-old was experiencing migraines, fatigue, and reactive hypoglycemia with a pants size that went from a 0 to a 12.These researchers hope that these preliminary findings will be confirmed with testing of more samples in the future.The authors stated that a drawback of OGM is the detection of whole arm translocations (Robertsonian translocations) and SVs located in telomeric regions due to the absence of labels in these regions.According to the Heart Failure Society of America's Practice Guideline on the genetic evaluation of cardiomyopathy (2009), the clinical utility for all genetic testing of cardiomyopathies remains to be defined.Moreover, most of the respondents felt happy about adopting a ketogenic diet and would recommend it to anyone who wants to lose weight.Whether you’re a workout beast or just a beginner making your first foray into the world of fitness and dieting – BetterMe has a lot to offer to both newbies and experts!Spinal muscular atrophy (SMA), which has an estimated prevalence of 1 in 10,000, is characterized by proximal muscle weakness resulting from the degeneration of anterior horn cells in the spinal cord. Cortisol is notorious for causing “stress belly,” which is the accumulation of fat around your midsection. For example, stress can affect the hormone cortisol, which can lead to weight gain. Lifestyle choices may impact different hormones in your body. So, if you’re going through any of these life stages, it’s important to be aware of how they may impact your body transformation. Pregnancy and breastfeeding can also impact hormones and cause weight gain. Migrainous vertigo is a term used to describe episodic vertigo in patients with a history of migraines or with other clinical features of migraine. Strasser et al (2012) stated that Alport syndrome (ATS) is a type-IV collagen inherited disorder, caused by mutations in COL4A3 and COL4A4 (autosomal recessive) or COL4A5 (X-linked). MODY1 makes up about 10 % of MODY cases in the United Kingdom … The most well-established treatment changes that can result from a genetic diagnosis are high-dose sulfonylureas rather than insulin for KCNJ11/ABCC8-related diabetes (usually neonatal), low-dose sulfonylureas rather than insulin (especially at early stages) for MODY1 (HNF4A) and MODY3 (HNF1A), and no treatment for MODY2 (GCK)”. Explore thousands of practical videos on keto, fasting, nutrition, and more–directly from The Knowledge Doc® Learn how to cut through the junk and fuel your body with whole, nutrient-dense foods. Explore practical strategies from a leading health expert to better understand your body and take control of your health. month Transformation Of A Father-Of-Three, 45 Years Old When trying to lose weight in 6 months, you can create an exercise plan that includes various movements. Getting help from a certified trainer or a reputable online platform is advisable to transform your body in 6 months. Yes, you can make visible changes to your body within 6 months. You can opt for a plant-based diet or a structured plan such as a 30-day fasting challenge. Research from 2018 found that some people can get better at breathing and build muscles in only two to four weeks. A c.428del base deletion in 0.1% of the general population was found with a second mutation in an additional set of 9 of 163 unexplained JS patients. Electrodiagnostic testing shows loss of sensory nerve action potentials with or without motor neuron involvement. To examine the effect of truncating variants on RFC1 expression, these investigators tested the level of RFC1 transcript and protein on patients' derived cell lines. After eight weeks subjects repeated the strength tests and body composition analysis and basal metabolism were reassessed 72 h after the last workout blood samplingGenetic testing generally is not recommended for patients with sporadic pulmonary fibrosis unless they or their family members display features suggestive of a genetic syndrome.Your ultimate resource for keto diet transformation with meal plans, success stories, and curated products that really work.It is expected that genetic analyses will have an important consequence in the screening of the relatives of HCM patients and also in the prenatal diagnostics and genetic counseling.Shephard and Semsarian (2009) stated that genetic heart disorders are an important cause of SCD in the young.Based on the frequency of splicing alterations in this multi-gene DGT cohort, these researchers expected that RGT results could potentially lead to variant re-classifications for at least 1 of 43 (2.3 %) patients undergoing genetic testing.I’ll have a couple fat bombs and some pecans.UpToDate reviews on "Diagnostic evaluation of women with suspected breast cancer" (Esserman and Joe, 2014a), "Clinical features, diagnosis, and staging of newly diagnosed breast cancer" (Esserman and Joe, 2014b), and "Clinical manifestations and diagnosis of a palpable breast mass" (Sabel, 2014) do not mention RAD51C gene testing. Ehlers-Danlos syndrome: “I wake up with my keto coffee, then after the gym I may have a protein shake. I eat a lot of canned sardines, or I’ll make a keto pudding out of whey protein, coconut cream, and cream cheese. I’ve cut out the protein bars and shakes and have so much energy. It’s just how I eat, so I have more time to help people with their weight loss transformations.” I did my research on the diet and decided keto was going to be the last thing that I try. In addition, single site MSH6 or PMS2 testing may be appropriate for testing family members of persons with HNPCC with an identified MSH6 or PMS2 gene mutation. Identifying individuals with this disease and performing screening colonoscopies on affected persons may help reduce colon cancer mortality. Hereditary non-polyposis colon cancer (HNPCC, Lynch syndrome) is one of the most common cancer predisposition syndromes affecting 1 in 200 individuals and accounting for 13 to 15 % of all colon cancer. HHT may be diagnosed clinically (using three or more Curaçao Criteria or by documentation of a pathogenic or likely pathogenic variant in an HHT gene. International consensus diagnostic criteria (the Curacao diagnostic criteria) are based upon four findings. An affected family member should be tested first to determine the causative mutation before testing an asymptomatic child who does not meet the clinical diagnostic criteria for HHT (Faughman et al, 2020). The primary reason people fail to follow through with their resolution to lose weight has to do with their approach to behavior change. Anyone CAN dramatically improve their body composition in three months, but not everyone WILL. A body transformation coach like Julie Lohre specializes in guiding women through comprehensive lifestyle changes to achieve significant physical transformations. She clearly understands the unique needs of a woman’s body (especially those of us over 40!) and really held me accountable through the whole process. The OtoGenome Test is a next-generation sequencing (NGS) assay that evaluates 110 genes in persons with apparent nonsyndromic and syndromic (e.g., Pendred syndrome, Usher syndrome) hearing loss. Even though consuming fish reduced the risk of ARMD in observational studies, the AREDS2 results showed that omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid/eicosapentaenoic acid) had no beneficial effect on ARMD. May be helpful in accurately diagnosing type 3 VWD.James and colleagues (2021) suggested targeted genetic testing over low-dose ristocetin-induced platelet agglutination (RIPA) to diagnose type 2B VWD for patients suspected of type 2A or 2B in need of additional testing. Substantial variation exists in attitude and practices related to genetic testing of patients and pre-symptomatic testing of their relatives across geographic regions and between experienced specialists in ALS and non-specialists. A total of 55.2 % of respondents would seek genetic testing if they had personally received a diagnosis of ALS; 42 % never offered pre-symptomatic testing to family members of patients with FALS. Most of the respondents (69.9%) reported that they adopted a ketogenic diet for more than one month. ” If the answer was no, then the participant was directed to a different questionnaire about diet in general. One of the first questions in the survey was “have you tried ketogenic diet? We targeted ketogenic diet groups on social media for over one month through messages and direct contact with group moderators and ensured that only people who practiced the ketogenic diet participated in the survey. Only 15 positive subjects participated in the follow-up, again resulting positive for serum p53Abs, and no evidence of cancer was found in these patients. These researchers performed a large prospective study, enrolling non-smokers, ex-smokers and smokers with or without the impairment of lung function, to analyze the incidence of serum p53Abs and the correlation with clinicopathologic features, in particular smoking habits and impairment of lung function, in order to investigate their possible role as early markers of the onset of lung cancer or other cancers. Mutant p53 accumulates early in cells and can precociously induce circulating anti-p53 antibodies (p53Abs); in fact, p53 over-expression has been observed in pre-neoplastic lesions, such as bronchial dysplasia, and p53Abs have been found in patients with chronic obstructive pulmonary disease, before the diagnosis of lung and other tobacco-related tumors. The most common gene mutation in LVNC include MYH7, MYBPC3, and TTN.Per GeneReviews (Legius and Stevenson, 2020), Legius syndrome, also known as neurofibromatosis type 1-like syndrome, is characterized by multiple café au lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1 (NF1). Common genes (1-10% of tested cases) considered definitive/strong evidence of HCM include MYL2, MYL3, and TNNI3. They state that this is a "cost-efficient way that enables the clinicians to determine who should be further screened and continue follow-up and who should be released from further follow-up or clinical testing and evaluation". Screening for a larger number of genes entails a much greater chance of variants of unknown significance (VUS) being involved in the final report, which may complicate the explanation of the results. Gartzonikas and colleagues (2023) state that "HCM is a diagnosis of exclusion since secondary causes of left ventricular hypertrophy should first be ruled out. These include hypertension, aortic stenosis, infiltrative disease, metabolic and endocrine disorders, mitochondrial cardiomyopathies, neuromuscular disorders, malformation syndromes and some chronic drug use".