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AimThis study aimed to monitor public interest in information related to Lipedema and examine potential temporal, seasonal, and income-related trends that may impact public interest.Material – MethodsA dataset was created using the Google Trends tool by inputting the keyword “Lipedema” to obtain the relative search volume (RSV) from 2004 to the present in the United States (US). To examine potential income-related disparities in public interest in Lipedema across the US, RSV values were recorded in the five states with the highest and the lowest median income (Maryland, New Hampshire, New Jersey, Utah, and Washington and Mississippi, West Virginia, Arkansas, New Mexico, Kentucky, respectively).ResultsPublic interest in Lipedema increased significantly over time (R2 = 0.693, p < .001 for the linear trend; R2 = 0.880, p < .001 for the quadratic trend). There were no significant differences between the RSV values between the month of the year and the season of the year (p = 1.000 and p = .859, respectively). RSV values of the five highest-income and low-income states showed significant increases (R2 = 0.333, p < .001, and R2 = 0.195, p < .001, respectively) More rapid growth in interest in Lipedema in states with high income compared to the states with low income (p < .001).ConclusionPublic interest in Lipedema is increasing in both high-income and low-income states. States with higher incomes are more interested. Searches for lipedema are expected to become more frequent, leading to a rising demand for comprehensive education in medical schools and clinician training programs. In addition, there will also be a need for easily accessible, high-quality information resources.

Gestrinone (R-2323), or ethylnorgestrienone, is a synthetic steroid of the 19-nortestosterone group more commonly used as an oral, intravaginal, or subcutaneous implant for the treatment of endometriosis, contraception, and estrogen-dependent conditions such as hypermenorrhea, premenstrual dysphoria, and intense menstrual cramps. This review aims to reevaluate the routes, doses, and applicability proposed for using gestrinone, including its use in new conditions such as menopause, lipedema, and sarcopenia. Here, we present the possible application of gestrinone as a long-acting therapeutic possibility through hormonal implants and the benefits and potential risks. Available evidence on the safety of doses and routes is limited. Gestrinone appears to be effective compared to other progestins and may have some advantages in the treatment of estrogen-dependent pathologies. Future research must evaluate gestrinone's long-term safety and potential therapeutic indications.

Background:  Lower limb swelling presents a diagnostic challenge with diverse causes, including well-known issues like venous insufficiency and lymphedema, and less-understood conditions like lipedema. Lipedema, involving abnormal fat accumulation in the lower extremities, is frequently misdiagnosed, posing challenges for affected individuals. This research aimed to report and analyze the clinical features of patients presenting with the complaint of lipedema. Methods:  A retrospective cross-sectional study was conducted in Saudi Arabia from April to November 2023, involving adult patients from a specialized clinic in lipedema and lymphedema management. Data were collected through clinical evaluation and a comprehensive data collection sheet. Results:  In a cohort of 115 female patients (mean age: 38.58), the most common age for disease onset was around 20–29 years. Physical examinations revealed symmetric enlargement (88%), collar sign (43%), orthostatic nonpitting edema (49%), and telangiectasia (64%). Varicose veins were present in 36%, Stemmer signs in 2%, and foot edema in 13%. Clinical diagnosis with lipedema occurred in 71%, with grade 2 (31%) as the most common severity and type 3 (47%) as the prevalent disease type. Conclusions:  The current study, the first of its kind in the Middle East and specifically in Saudi Arabia, emphasizes the urgency of increased awareness and intervention due to a high underdiagnosis rate in lipedema. The observed complexity in symptoms and correlations between severity, lymphatic impairment, and body mass index underscore lipedema’s multifaceted nature. Future research should explore regional and cultural influences and conduct larger studies to validate and recognize various lipedema features.

BACKGROUND: Lipoedema is a painful adipose tissue disorder, affecting the limbs of women, that is resistant to diet and exercise. The purpose of the study was to evaluate the retrospective health-related quality-of-life (HRQoL) outcomes for patients with lower limb lipoedema (LLL) following tumescent liposuction (TL). METHODS: Forty-seven patients received TL over 5 years from 2015-2020 for LLL. As part of their routine treatment evaluation, each patient completed 4 validated HRQoL questionnaires at initial assessment. The questionnaires examined the patients' experiences relating to anxiety and depression, lower extremity function, appearance, and symptoms. The same questionnaires were posted to the patients after an average of 12 months post-procedure/s to establish the outcomes of the intervention. RESULTS: The study demonstrated that patients' HRQoL improved at 12 months (average) following TL. The results of all the questionnaires were statistically significant, and patients with stage 3 LLL showed the most improvement in outcomes. CONCLUSION: The findings demonstrated that TL achieves positive HRQoL outcomes in patients with LLL; however, long-term follow-up is needed to determine if the benefits sustain. Additionally, larger prospective controlled studies are required to provide robust evidence for this procedure.

Body composition (BC) measured by DXA differs between devices. We aimed to compare regional and total BC measurements assessed by the Hologic Horizon A and the GE Lunar iDXA devices; to determine device-specific calibration equations for each BC parameter; and to assess the impact of this standardization procedure on the assessment of sarcopenia, lipedema, obesity, and cardiovascular risk with DXA. A total of 926 postmenopausal women (aged 72.9 ± 6.9 yr, height 160.3 ± 6.6 cm, weight 66.1 ± 12.7 kg) underwent BC assessment on each device within 1 h, following the ISCD guidelines. The included sample was split into 80% train and 20% test datasets stratified by age, height, and weight. Inter-device differences in BC parameters were assessed with Bland-Altman analysis, Pearson or Spearman correlation coefficients, and t-tests or Wilcoxon tests. The equations were developed in the train dataset using backward stepwise multiple linear regressions and were evaluated in the test dataset with the R-squared and mean absolute error. We compared the abovementioned BC-derived health conditions before and after standardization in the test set with respect to relative risk, accuracy, Kappa score, and McNemar tests. Total and regional body masses were similar (p>.05) between devices. BMC was greater for all regions in the Lunar device (p<.05), while fat and lean masses differed among regions. Regression equations showed high performance metrics in both datasets. The BC assessment from Hologic classified 2.13 times more sarcopenic cases (McNemar: p<.001), 1.39 times more lipedema (p<.001), 0.40 times less high cardiovascular risk (p<.001), and similarly classified obesity (p>.05), compared to Lunar. After standardization, the differences disappeared (p>.05), and the classification metrics improved. This study discusses how hardware and software differences impact BC assessments. The provided standardization equations address these issues and improve the agreement between devices. Future studies and disease definitions should consider these differences.

This S2k guideline was developed on the initiative and under the German Society of Phlebology and Lymphology (DGPL) leadership. The guideline aims to optimize the diagnosis and treatment of lipedema. It is intended to bring together the different approaches of the respective professional groups in a consensus-based manner and thus offer a basic concept for the best possible treatment of patients with lipedema. Sixty recommendations were formulated and agreed on in diagnostics, conservative and surgical treatment options, psychosocial factors and self-management. The guideline is intended to reflect the current scientific knowledge and be widely used for diagnosis and treatment recommendations for patients with lipedema. In particular, the guideline comments on diagnostic criteria, differential diagnoses, and coinciding clinical pictures, their influence on diagnosis and treatment, sensible treatment measures, and self-management options. The lipedema guideline summarizes the current national and international evidence and the German expert consensus and derives recommendations for the best treatment for patients with lipedema. The recommendations in the guideline are intended as an orientation aid in the sense of action and decision-making corridors from which deviations are possible in justified cases.

Introduction Lipedema is a relatively common, frequently misdiagnosed, chronic condition often treated by liposuction when conservative therapies fail. Techniques such as traditional tumescent liposuction (TTL), power-assisted liposuction (PAL), and water-jet-assisted liposuction (WAL), are popular surgical interventions, although it is unclear how these techniques compare. This meta-analysis aims to assess the efficacy and safety of liposuction in patients with lipedema. Methods Relevant English lipedema studies published in PubMed from January 2003 to April 2023 were identified. Ten articles with postoperative outcomes and complications data were included (2 TTL, 5 PAL, 1 WAL, 2 articles used both PAL and WAL). Results were summarized using descriptive statistics, and a randomized effects model was used to evaluate heterogeneity. Results A total of 2,542 procedures in 906 patients were included. Combined outcomes for all techniques significantly improved pain, bruising, edema, tension, pressure sensitivity, cosmetic impairment, and general impairment (all P < 0.00001). Results for TTL, PAL, and WAL led to significant improvements in pain reduction (P = 0.0005), bruising, swelling, pressure sensitivity, or cosmetic impairment (all P < 0.05). WAL more effectively reduced tension and general impairment (all P < 0.005), but heterogeneity for these outcomes was high. Overall complication rates were low for studies that utilized TTL (1.5%), PAL (4.0%), WAL (0%), and both PAL and WAL (2.3%). Conclusion Liposuction techniques, including TTL, PAL, and WAL, result in significant symptom improvement in lipedema patients with a relatively low complication rate. WAL may potentially result in a more substantial reduction of tension and general impairment with fewer complications; however, only a single study performed this method of liposuction exclusively. This is the first meta-analysis investigating liposuction data in lipedema treatment.

We evaluated the effect of compression leggings with micromassage in association with physical activity on women with lipedema, not previously treated and without recent changes in body weight. The treatment resulted in an improvement in all subjective parameters, in spontaneous and evoked pain, in the volume of the limbs, in the absence of significant changes in body weight, and regardless of the duration of use, age, years of illness, the clinical stage, and body mass index (BMI). Evoked pain did not improve in areas affected by untreated lipedema; foot circumferences did not increase. We found a significant reduction in the thickness of subcutaneous adipose tissue (SAT) and skin evaluated in multiple points of the lower limb. Micromassage compression leggings are proposed as an integral part of conservative treatment. A method is proposed for the clinical evaluation of evoked pain, called the Progressive Pain Check (PPC), which allows for the calculation of a numerical score called the Ricolfi-Patton Score (RPS) and for the ultrasound evaluation of tissues. The method is simple and repeatable and allows for completion of the clinical evaluation of the patient at diagnosis and for an evaluation of the effects of various treatments, even applied to just one side of the body.

PURPOSE OF REVIEW: This consensus statement from the Italian Society of Motor and Sports Sciences (Società Italiana di Scienze Motorie e Sportive, SISMeS) and the Italian Society of Phlebology (Società Italiana di Flebologia, SIF) provides the official view on the role of exercise as a non-pharmacological approach in lipedema. In detail, this consensus statement SISMeS - SIF aims to provide a comprehensive overview of lipedema, focusing, in particular, on the role played by physical exercise (PE) in the management of its clinical features. RECENT FINDINGS: Lipedema is a chronic disease characterized by abnormal fat accumulation. It is often misdiagnosed as obesity, despite presenting distinct pathological mechanisms. Indeed, recent evidence has reported differences in adipose tissue histology, metabolomic profiles, and gene polymorphisms associated with this condition, adding new pieces to the complex puzzle of lipedema pathophysiology. Although by definition lipedema is a condition resistant to diet and PE, the latter emerges for its key role in the management of lipedema, contributing to multiple benefits, including improvements in mitochondrial function, lymphatic drainage, and reduction of inflammation. Various types of exercise, such as aquatic exercises and strength training, have been shown to alleviate symptoms and improve the quality of life of patients with lipedema. However, standardized guidelines for PE prescription and long-term management of patients with lipedema are lacking, highlighting the need for recommendations and further research in this area in order to optimise therapeutic strategies.

Lymphological and fatty tissue disorders of the legs are increasingly tying up capacities in the health care system. This is related to the increase in obesity disease to almost endemic proportions in our society. Although the term lipedema was coined in the 1950s, it has only now become really well known. Women with lipedema suffer from symmetrical and disproportional fat deposition on both legs, accompanied by tenderness or strong pain especially on touch. Over 50 years, this condition has been underdiagnosed. Women with lipohypertrophy (same fat disproportion without pain) fear they suffer from lipedema and are misguided by false information, claiming treatment, as well as liposuction reimbursed by health care systems. Affected women suffer greatly from misinformation but also from overdiagnosis. The aim of this work is to make differential diagnosis easier for the health practitioner. On the basis of descriptions on visual inspection and palpation of the affected legs, the differential diagnosis is explained here, supported with many pictures. As a result, differentiation of the entities lipedema, lipohypertrophy, obesity, and lymphedema and their mixed forms is made easier for health practitioners in their daily work. Many studies are still needed to better understand the entity lipedema, and efforts are underway to change the name to avoid misunderstandings, as the condition “lipedema” does not seem to have water in the fatty tissue.

Lymphedema and lipedema are chronic debilitating disorders that most commonly affect the upper and lower extremities. Although they can appear similar, they differ in important ways, which the authors of this article review and contrast.

BACKGROUND: Lipedema is the progressive symmetrical deposition of subcutaneous fat and fluid in the lower body, ordinarily sparing the trunk, upper limbs, face, and neck. It may follow an autosomal dominant inheritance pattern. The gold standard treatment for lipedema is complete decongestive therapy, consisting of manual lymphatic drainage and compression garments. This scoping review assessed the existing literature on the effectiveness of liposuction as an alternative treatment for lipedema. METHODS: A scoping review of electronically available literature within PubMed, Scopus, and Cochrane focused on liposuction as a treatment for lipedema considering the following inclusion criteria: human studies, case series of 10 or more, controlled trials, randomized controlled trials, patient-reported outcome measurement studies, survey analyses, descriptive studies, retrospective analyses, recurrence included, follow-up of 6 months or more, age 18 years or older, and treatment modality being liposuction. RESULTS: Thirteen studies were selected. Nine studies reported decreased compression therapy use among patients following liposuction. No studies reported a long-term increase in compression therapy following liposuction. Studies found self-reported improvements in pain, mobility, bruising, and overall quality of life for patients following liposuction, many of whom had previously been on compressive therapy. Studies reported low rates of serious adverse events following liposuction, including deep vein thrombosis, pulmonary embolism, and infection. CONCLUSIONS: These results suggest that liposuction can be a viable treatment alternative to compression therapy for lipedema in patients whose compression therapy has not been helpful. However, there is not enough evidence to say whether liposuction is as effective as compression for patients first presenting with lipedema.

The core content for a medical specialty outlines the scope of the discipline as well as the categories of knowledge considered essential to practice in the field. It provides a template for the development of curricula for medical school, graduate, and postgraduate education, as well as for creating certification standards. Venous and Lymphatic Medicine (VLM) is a specialty that has benefitted from contributions from specialists from several medical disciplines. Optimally, the societies, boards, and residency review committees representing these disciplines would uniformly recognize the scope of VLM to develop education and assessment standards to allow training and identification of qualified practitioners. In order to inform the standard setting bodies and other stakeholders of the current scope of VLM, a task force of VLM experts from cardiology, dermatology, emergency medicine, general surgery, interventional radiology, vascular medicine, and vascular surgery was formed to revise a 2014 consensus document defining the core content of the specialty of VLM.

The validated Dutch translation showed high values for internal consistency, test-retest reliability, and validity, which allows us to implement the questionnaire in the early detection of LEL after gynecological cancer treatment.

Background: Despite its increasing incidence and prevalence throughout Western countries, lipedema continues to be a very enigmatic disease, often misunderstood or misdiagnosed by the medical community and with an intrinsic pathology that is difficult to trace. The nature of lipedemic tissue is one of hypertrophic adipocytes and poor tissue turnover. So far, there are no identified pathways responsible, and little is known about the cell populations of lipedemic fat. Methods: Adipose tissue samples were collected from affected areas of both lipedema and healthy participants. For single-cell RNA sequencing analysis, the samples were dissociated into single-cell suspensions using enzymatic digestion and then encapsulated into nanoliter-sized droplets containing barcoded beads. Within each droplet, cellular mRNA was converted into complementary DNA. Complementary DNA molecules were then amplified for downstream analysis. Results: The single-cell RNA-sequencing analysis revealed three distinct adipocyte populations at play in lipedema. These populations have unique gene signatures which can be characterized as a lipid generating adipocyte, a disease catalyst adipocyte, and a lipedemic adipocyte. Conclusions: The single-cell RNA sequencing of lipedemic tissue samples highlights a triad of distinct adipocyte subpopulations, each characterized by unique gene signatures and functional roles. The interplay between these adipocyte subtypes offers promising insights into the complex pathophysiology of lipedema.

Lipedema and lymphedema are physically similar yet distinct diseases that are commonly misdiagnosed. We previously reported that lipedema and lymphedema are associated with increased risk for venous thromboembolism (VTE). The underlying etiology of the prothrombotic profile observed in lipedema and lymphedema is unclear, but may be related to alterations in platelets. Our objective was to analyze the platelet transcriptome to identify biological pathways that may provide insight into platelet activation and thrombosis. The platelet transcriptome was evaluated in patients with lymphedema and lipedema, then compared to control subjects with obesity. Patients with lipedema were found to have a divergent transcriptome from patients with lymphedema. The platelet transcriptome and impacted biological pathways in lipedema were surprisingly similar to weight-matched comparators, yet different when compared to overweight individuals with a lower body mass index (BMI). Differences in the platelet transcriptome for patients with lipedema and lymphedema were found in biological pathways required for protein synthesis and degradation, as well as metabolism. Key differences in the platelet transcriptome for patients with lipedema compared to BMI-matched subjects involved metabolism and glycosaminoglycan processing. These inherent differences in the platelet transcriptome warrant further investigation, and may contribute to the increased risk of thrombosis in patients with lipedema and lymphedema.

Abstract Background Lipedema is a chronic, incurable disorder characterized by painful fat accumulation in the extremities. While the application of liposuction in lipedema management has become increasingly popular, the safety and effectiveness of this approach remain contentious. Our systematic review and meta-analysis aimed to assess various liposuction modalities in lipedema management to verify their safety and efficacy. Methods In-line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a comprehensive literature review from inception until March 2023 using the following electronic databases: CENTRAL, MEDLINE, Google Scholar, and EMBASE. Results From the 562 initially identified articles, 20 met our inclusion/exclusion criteria for evaluation. Our review encompassed 14 prospective cohort studies, 3 retrospective studies, 2 case series, and 1 cross-sectional study. A meta-analysis of nine articles revealed a notable improvement in the quality of life, pain, pressure sensitivity, bruising, cosmetic impairment, heaviness, walking difficulty, and itching among lipedema patients who underwent liposuction. Although complications such as inflammation, thrombosis, seroma, hematoma, and lymphedema-related skin changes were reported, severe complications were rare. Crucially, no instances of shock, recurrence, or mortality were reported. Conclusion Liposuction is a safe and beneficial therapeutic intervention for managing lipedema symptoms and enhancing quality of life. However, the impact of liposuction on secondary lymphedema remains unreported in the literature. Further high-quality, large-scale trials are necessary to assess the safety and effectiveness of different liposuction modalities. These studies will contribute valuable insights to optimize liposuction as a therapeutic option for individuals with lipedema. Level of Evidence I, risk/prognostic study.

RATIONALE: TRPV4 channels are critical regulators of blood vascular function and have been shown to be dysregulated in many disease conditions in association with inflammation and tissue fibrosis. These are key features in the pathophysiology of lymphatic system diseases, including lymphedema and lipedema; however, the role of TRPV4 channels in the lymphatic system remains largely unexplored. TRPV4 channels are calcium permeable, non-selective cation channels that are activated by diverse stimuli, including shear stress, stretch, temperature, and cell metabolites, which may regulate lymphatic contractile function. OBJECTIVE: To characterize the expression of TRPV4 channels in collecting lymphatic vessels and to determine the extent to which these channels regulate the contractile function of lymphatics. METHODS AND RESULTS: Pressure myography on intact, isolated, and cannulated lymphatic vessels showed that pharmacological activation of TRPV4 channels with GSK1016790A (GSK101) led to contractile dysregulation. The response to GSK101 was multiphasic and included, 1) initial robust constriction that was sustained for ≥1 minute and in some instances remained for ≥4 minutes; and 2) subsequent vasodilation and partial or complete inhibition of lymphatic contractions associated with release of nitric oxide. The functional response to activation of TRPV4 channels displayed differences across lymphatics from four anatomical regions, but these differences were consistent across different species (mouse, rat, and non-human primate). Importantly, similar responses were observed following activation of TRPV4 channels in arterioles. The initial and sustained constriction was prevented with the COX inhibitor, indomethacin. We generated a controlled and spatially defined single-cell RNA sequencing (scRNAseq) dataset from intact and microdissected collecting lymphatic vessels. Our data uncovered a subset of macrophages displaying the highest expression of Trpv4 compared to other cell types within and surrounding the lymphatic vessel wall. These macrophages displayed a transcriptomic profile consistent with that of tissue-resident macrophages (TRMs), including differential expression of Lyve1 , Cd163 , Folr2 , Mrc1 , Ccl8 , Apoe , Cd209f , Cd209d , and Cd209g ; and at least half of these macrophages also expressed Timd4. This subset of macrophages also highly expressed Txa2s , which encodes the thromboxane A2 (TXA2) synthase. Inhibition of TXA2 receptors (TXA2Rs) prevented TRPV4-mediated contractile dysregulation. TXA2R activation on LMCs caused an increase in mobilization of calcium from intracellular stores through Ip3 receptors which promoted store operated calcium entry and vasoconstriction. CONCLUSIONS: Clinical studies have linked cancer-related lymphedema with an increased infiltration of macrophages. While these macrophages have known anti-inflammatory and pro-lymphangiogenic roles, as well as promote tissue repair, our results point to detrimental effects to the pumping capacity of collecting lymphatic vessels mediated by activation of TRPV4 channels in macrophages. Pharmacological targeting of TRPV4 channels in LYVE1-expressing macrophages or pharmacological targeting of TXA2Rs may offer novel therapeutic strategies to improve lymphatic pumping function and lymph transport in lymphedema.

The role of artificial intelligence (AI) in healthcare is evolving, offering promising avenues for enhancing clinical decision making and patient management. Limited knowledge about lipedema often leads to patients being frequently misdiagnosed with conditions like lymphedema or obesity rather than correctly identifying lipedema. Furthermore, patients with lipedema often present with intricate and extensive medical histories, resulting in significant time consumption during consultations. AI could, therefore, improve the management of these patients. This research investigates the utilization of OpenAI's Generative Pre-Trained Transformer 4 (GPT-4), a sophisticated large language model (LLM), as an assistant in consultations for lipedema patients. Six simulated scenarios were designed to mirror typical patient consultations commonly encountered in a lipedema clinic. GPT-4 was tasked with conducting patient interviews to gather medical histories, presenting its findings, making preliminary diagnoses, and recommending further diagnostic and therapeutic actions. Advanced prompt engineering techniques were employed to refine the efficacy, relevance, and accuracy of GPT-4's responses. A panel of experts in lipedema treatment, using a Likert Scale, evaluated GPT-4's responses across six key criteria. Scoring ranged from 1 (lowest) to 5 (highest), with GPT-4 achieving an average score of 4.24, indicating good reliability and applicability in a clinical setting. This study is one of the initial forays into applying large language models like GPT-4 in specific clinical scenarios, such as lipedema consultations. It demonstrates the potential of AI in supporting clinical practices and emphasizes the continuing importance of human expertise in the medical field, despite ongoing technological advancements.

Background: Lipedema is a subcutaneous adipose tissue disorder characterized by increased pathological adipocytes mainly in the extremities. Vitamin D is stored in adipocytes, and serum levels inversely correlate with BMI. As adipocytes are removed during liposuction, lipedema patients might be prone to further substantial vitamin D loss while their levels are already decreased. Therefore, we examined the effect of liposuction on perioperative serum 25-hydroxyvitamin D levels. Methods: In patients undergoing lipedema liposuction, blood samples were obtained pre- and postoperatively. Statistical analyses were performed to correlate the volume of lipoaspirate, patients' BMI and number of sessions to vitamin D levels. Results: Overall, 213 patients were analyzed. Mean liposuction volume was 6615.33 ± 3884.25 mL, mean BMI was 32.18 ± 7.26 kg/m2. mean preoperative vitamin D levels were 30.1 ± 14.45 ng/mL (borderline deficient according to the endocrine society) and mean postoperative vitamin D levels were 21.91 ± 9.18 ng/mL (deficient). A significant decrease in serum vitamin D was seen in our patients (p < 0.001) of mean 7.83 ng/mL. The amount of vitamin D loss was not associated with BMI or aspiration volume in our patients (p > 0.05). Interestingly, vitamin D dynamics showed a steady drop regardless of volume aspirated or preoperative levels. Conclusions: Many lipedema patients have low vitamin D levels preoperatively. Liposuction significantly reduced these levels additionally, regardless of aspirated volume or BMI. However, vitamin D loss was constant and predictable; thus, patients at risk are easily identified. Overall, lipedema patients undergoing liposuction are prone to vitamin D deficiency, and the long-term effects in this population are currently unknown.