Challenging conventions: Reconsidering the indication for endovenous ablation in CEAP 2 patients.

INTRODUCTION: Endovenous ablation may not always be necessary for every patient with chronic venous insufficiency who has an indication for endovenous ablation. This study investigates whether compression stockings and Daflon® can be as effective for some patients with CEAP two in chronic venous insufficiency. METHODS: In this study, 137 patients who had endovenous ablation indication received plethysmographical hemodynamic tests and were divided into two groups. Group 1 had normal venous hemodynamics and received compression stockings and Daflon®. Group 2 had abnormal function and received laser ablation. All patients were reevaluated after 6 months. RESULTS: The study showed that there was no statistically significant difference between Groups 1 and 2 in the 6th month measurements after the treatments. CONCLUSION: As a result, we do not find it appropriate and do not recommend that every patient with complaints of chronic venous insufficiency and an indication for endovenous ablation undergo ablation without evaluating lower extremity venous hemodynamics.

Multi-inflammatory index as a novel predictor of new-onset atrial fibrillation after off-pump coronary artery bypass grafting.

BACKGROUND: To our knowledge, a possible predictive relationship of the multi-inflammatory index (MII) with new-onset atrial fibrillation (AF) after off-pump coronary artery bypass grafting (CABG) has not yet been studied in the literature. AIMS: We aimed to investigate whether the MII is a novel group of hematological markers for predicting postoperative new-onset AF in patients undergoing off-pump CABG. METHODS: A total of 427 patients undergoing isolated off-pump CABG between October 2021 and December 2023 were enrolled in this retrospective observational cohort study and allocated to two groups: the AF group (n = 108) and the non-AF group (n = 319). The groups were compared in terms of baseline clinical patient characteristics, laboratory parameters, and operative and postoperative data. RESULTS: The median values of age, length of hospital stay, platelet and neutrophil count, C-reactive protein level, systemic immune-inflammation index, MII-1, MII-2, and MII-3 were significantly greater in the AF group compared to the non-AF group in univariate analyses. In multiple explanatory variable logistic regression analysis, MII-1, MII-2, and MII-3 were determined to be significant hematological variables, and thereby these indices were considered the independent predictors of postoperative new-onset AF. Receiver operating characteristic curve analyses showed that to predict postoperative new-onset AF, MII-1 of 22.47 constituted the cut-off value with 62.0% sensitivity and 57.0% specificity, MII-2 of 141.77 constituted the cut-off value with 43.5% sensitivity and 76.8% specificity, and MII-3 of 5669 constituted the cut-off value with 63.8% sensitivity and 58.3% specificity. CONCLUSION: This study demonstrated for the first time that all MIIs predicted new-onset AF after off-pump CABG.

Zoonotic and Zooanthroponotic Potential of Monkeypox.

The current multicounty outbreak of monkeypox virus (MPXV) posed an emerging and continued challenge to already strained public healthcare sector, around the globe. Since its first identification, monkeypox disease (mpox) remained enzootic in Central and West African countries where reports of human cases are sporadically described. Recent trends in mpox spread outside the Africa have highlighted increased incidence of spillover of the MPXV from animal to humans. While nature of established animal reservoirs remained undefined, several small mammals including rodents, carnivores, lagomorphs, insectivores, non-human primates, domestic/farm animals, and several species of wildlife are proposed to be carrier of the MPXV infection. There are established records of animal-to-human (zoonotic) spread of MPXV through close interaction of humans with animals by eating bushmeat, contracting bodily fluids or trading possibly infected animals. In contrast, there are reports and increasing possibilities of human-to-animal (zooanthroponotic) spread of the MPXV through petting and close interaction with pet owners and animal care workers. We describe here the rationales and molecular factors which predispose the spread of MPXV not only amongst humans but also from animals to humans. A range of continuing opportunities for the spread and evolution of MPXV are discussed to consider risks beyond the currently identified groups. With the possibility of MPXV establishing itself in animal reservoirs, continued and broad surveillance, investigation into unconventional transmissions, and exploration of spillover events are warranted.

Molecular Virology of Orthopoxviruses with Special Reference to Monkeypox Virus.

Poxviruses are large (200-450 nm) and enveloped viruses carrying double-stranded DNA genome with an epidermal cell-specific adaptation. The genus Orthopoxvirus within Poxviridae family constitutes several medically and veterinary important viruses including variola (smallpox), vaccinia, monkeypox virus (MPXV), and cowpox. The monkeypox disease (mpox) has recently emerged as a public health emergency caused by MPXV. An increasing number of human cases of MPXV have been documented in non-endemic nations without any known history of contact with animals brought in from endemic and enzootic regions, nor have they involved travel to an area where the virus was typically prevalent. Here, we review the MPXV replication, virus pathobiology, mechanism of viral infection transmission, virus evasion the host innate immunity and antiviral therapies against Mpox. Moreover, preventive measures including vaccination were discussed and concluded that cross-protection against MPXV may be possible using antibodies that are directed against an Orthopoxvirus. Despite the lack of a specialised antiviral medication, several compounds such as Cidofovir and Ribavirin warrant consideration against mpox.

Interferon-induced protein with tetratricopeptide repeats 5 of black fruit bat (Pteropus alecto) displays a broad inhibition of RNA viruses.

Bats are natural host reservoirs and have adapted a unique innate immune system that permits them to host many viruses without exhibiting symptoms. Notably, bat interferon stimulated genes (ISGs) have been shown to play antiviral roles. Interferon induced protein with tetratricopeptide repeats 5 (IFIT5) is a well-characterised ISG in humans with antiviral activities against negative-sense RNA viruses via inhibiting viral transcription. Here, we aim to investigate if Pteropus alecto (pa) IFIT5 (paIFIT5) possess the ability to inhibit negative-sense RNA viruses. Initially, gene syntenic and comparative structural analyses of multiple animals highlighted a high level of similarity between Pteropus alecto and human IFIT5 proteins. Our results showed that paIFIT5 was significantly inducible by viral and dsRNA stimulation. Transient overexpression of paIFIT5 inhibited the replication of vesicular stomatitis virus (VSV). Using minireplicon and transcription reporter assays, we demonstrated the ability of paIFIT5 specifically to inhibit H17N10 polymerase activity. Mechanistically, we noticed that the antiviral potential of paIFIT5 against negative sense RNA viruses was retributed to its interaction with 5'ppp containing RNA. Taken together, these findings highlight the genetic and functional conservation of IFIT5 among mammals.

Evaluation of the dynamic thiol/disulfide homeostasis in patients with chronic venous insufficiency.

OBJECTIVE: There is no study in the literature evaluating the dynamic thiol/disulfide homeostasis in patients with chronic venous insufficiency. Thus, we designed this study to evaluate the dynamic thiol/disulfide homeostasis as a novel indicator of oxidative stress in patients with chronic venous insufficiency. METHODS: This was a prospective case-control study performed at the department of cardiovascular surgery of a tertiary referral hospital in Turkey. A total of 80 (CEAP C3-C6) patients with lower extremity chronic venous insufficiency (as the study group) and 80 healthy subjects (as the control group) were enrolled to the study. The participants' basic demographic and clinical characteristics as well as serum levels of some laboratory parameters including albumin, ferroxidase, myeloperoxidase, native thiol, total thiol, disulphide, native thiol/total thiol, disulphide/native thiol, and disulphide/total thiol were determined, and then compared between the groups. RESULTS: In terms of basic demographic and clinical characteristics, both groups were statistically similar, and there were no significant differences between the groups. When the laboratory parameters were considered, serum ferroxidase and myeloperoxidase levels were detected to be significantly higher, whereas albumin, native thiol, total thiol, and disulphide levels were detected to be significantly lower in the study group than in the control group. CONCLUSIONS: Dynamic thiol/disulphide homeostasis could be considered as an indicator reflecting the oxidative stress status in patients with chronic venous insufficiency.

Avian sarcoma/leukosis virus (RCAS)-mediated over-expression of IFITM3 protects chicks from highly pathogenic avian influenza virus subtype H5N1.

Broad-spectrum antiviral activities of interferon-induced transmembrane proteins (IFITMs) are primarily attributed to in vitro inhibition of viral entry. Here, we used an avian sarcoma-leukosis virus (RCAS)-based gene transfer system and successfully generated chicks that constitutively express chicken IFITM3 (chIFITM3). The chIFITM3-overexpressing chicks showed significant protection and disease tolerance against highly pathogenic avian influenza virus (HPAIV) H5N1 (Clade 2.2.1.2). The chicks, overexpressing chIFITM3, also showed delayed onset of clinical symptoms, reduced viral shedding, and alleviated histopathologic alterations compared to control and challenged chicks. These findings highlight that overexpression of chIFITM3 provide a substantial defense against zoonotic H5N1 in vivo.

Deep Structural Analysis of Myriads of Omicron Sub-Variants Revealed Hotspot for Vaccine Escape Immunity.

The emergence of the Omicron variant has reinforced the importance of continued SARS-CoV-2 evolution and its possible impact on vaccine effectiveness. Specifically, mutations in the receptor-binding domain (RBD) are critical to comprehend the flexibility and dynamicity of the viral interaction with the human agniotensin-converting enzyme 2 (hACE2) receptor. To this end, we have applied a string of deep structural and genetic analysis tools to map the substitution patterns in the S protein of major Omicron sub-variants (n = 51) with a primary focus on the RBD mutations. This head-to-head comparison of Omicron sub-variants revealed multiple simultaneous mutations that are attributed to antibody escape, and increased affinity and binding to hACE2. Our deep mapping of the substitution matrix indicated a high level of diversity at the N-terminal and RBD domains compared with other regions of the S protein, highlighting the importance of these two domains in a matched vaccination approach. Structural mapping identified highly variable mutations in the up confirmation of the S protein and at sites that critically define the function of the S protein in the virus pathobiology. These substitutional trends offer support in tracking mutations along the evolutionary trajectories of SAR-CoV-2. Collectively, the findings highlight critical areas of mutations across the major Omicron sub-variants and propose several hotspots in the S proteins of SARS-CoV-2 sub-variants to train the future design and development of COVID-19 vaccines.

In Chronic Spontaneous Urticaria, Complete Response to Antihistamine Treatment Is Linked to Low Disease Activity.

INTRODUCTION: The use of predictors of response to a specific treatment in patients with chronic spontaneous urticaria (CSU) can improve disease management, help prevent unnecessary healthcare costs, and save time. In this study, we aimed to identify predictors of complete response to standard-dosed and higher than standard-dosed antihistamine treatments in patients with CSU. METHODS: Medical records of 475 CSU patients, 120 of them <18 years old, from 3 different centers were analyzed. We used 15 machine learning (ML) models as well as traditional statistical methods to predict complete response to standard-dosed and higher than standard-dosed antihistamine treatment based on 17 clinical parameters. RESULTS: CSU disease activity, which was assessed by urticaria activity score (UAS), was the only clinical parameter that predicted complete response to standard-dosed and higher than standard-dosed antihistamine treatment, with ML models and traditional statistics, for all age groups. Based on ROC analyses, optimal cut-off values of disease activity to predict complete response were UAS <3 and UAS <4 for standard-dosed (area under the ROC curve [AUC] = 0.69; p = 0.001) and higher than standard-dosed (AUC = 0.79; p = 0.001) antihistamine treatments, respectively. Also, ML models identified lower total IgE (<150 IU/mL) as a predictor of complete response to a standard-dosed antihistamine and lower CRP (<3.4 mg/mL) as a predictor of complete response to higher than standard-dose antihistamine treatment. DISCUSSION: In this study, we showed that patients with UAS <3 are highly likely to have complete response to standard-dosed AH and those with a UAS <4 are highly likely to have complete response to higher than standard-dosed AH treatment. Low CSU disease activity is the only universal predictor of complete response to AH treatment with both ML models and traditional statistics for all age groups.

Eating Increases and Exercise Decreases Disease Activity in Patients With Symptomatic Dermographism.

BACKGROUND: Eating can increase disease activity in patients with symptomatic dermographism , the most common subtype of chronic inducible urticaria, but it is unclear how common this is. The effects of exercising on symptomatic dermographism disease activity have also not yet been determined. OBJECTIVE: To assess the impact of exercise and nonspecific carbohydrate-rich food intake on the severity and intensity of symptomatic dermographism after exercise and nonspecific carbohydrate-rich food intake. METHODS: We assessed disease activity by FricTest provocation testing in 75 symptomatic dermographism patients before and after eating, exercising, or both. We determined the rates of food-dependent (FD) symptomatic dermographism and food-exacerbated (FE) symptomatic dermographism. By comparing post- and pre-exercise FricTest scores, we identified complete responders: that is, patients with a negative FricTest response after exercising and partial responders. Finally, we evaluated whether exercise protects patients with FD-symptomatic dermographism or FE-symptomatic dermographism from eating-induced worsening of symptomatic dermographism. RESULTS: Of 64 symptomatic dermographism patients, eight had FD-symptomatic dermographism (13%), 42 had FE-symptomatic dermographism (66%), and 14 patients showed no negative impact of eating on disease activity (21%). Physical exercise reduced FricTest skin provocation test responses in 83% of 58 patients. Exercising protected patients with FD/FE-symptomatic dermographism from worsening of symptomatic dermographism owing to eating in half of cases, with higher rates for exercise after eating (67%) compared with exercise before eating (35%). CONCLUSIONS: Our study shows that eating often worsen symptomatic dermographism symptoms, and exercise often improves it. Our findings might aid patients in controlling symptoms better.

The relationship between hidradenitis suppurativa and irritable bowel syndrome: a cross-sectional study.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which one experiences abdominal pain, tension, cramping, bloating, and changes in the form and frequency of defecation, without an underlying organic disease. Many skin diseases have been reported to be more common in people with functional bowel disease. To our knowledge, however, no previous study investigated the potential relationship between hidradenitis suppurativa (HS) and IBS. In this study, we aimed to examine the potential association between IBS and HS. METHODS: Patients with HS and healthy subjects were enrolled in this cross-sectional study. All participants were assessed for the presence of IBS. ROME IV criteria were used to identify IBS cases. Hurley staging, modified Sartorius score, and physician's global assessment score were applied to define clinical severity and staging of HS. RESULTS: According to the Rome IV diagnostic criteria, 54 (67.50%) of 80 HS patients and 23 (28.75%) of 80 control group were diagnosed with IBS. The frequency of IBS was statistically significantly higher in the patient group than in the control group (P < 0.001). No statistically significant difference was found between the two groups in terms of abnormal stool frequency and family history of IBS (P = 0.28, P = 0.862, respectively). Abnormal stool form, mucus in stool, abdominal distension, feeling of incomplete evacuation were statistically significantly higher in HS patients compared to the controls (P = 0.01, P = 0.02, P < 0.001, P = 0.001, respectively).

Genetic diversity, frequency and concurrent infections of picobirnaviruses in diarrhoeic calves in Turkey.

Calf diarrhoea is one of the major problems in cattle farming with high morbidity and mortality in herds. Two enteric viruses, bovine rotavirus (BRV) and bovine coronavirus (BCoV), are the leading cause of gastroenteritis in young calves, whereas picobirnaviruses (PBVs) are often associated with diarrhoea. In the present study, the faecal specimens of 127 diarrhoeic bovines (less than 1-month-old) were employed to investigate the infection frequencies of these three pathogens. Results indicated that frequencies of BRV and BCoV in diarrhoeic calves were 38.58% and 29.92%, respectively. The 7.08% of bovine calf samples (9 out of 127) were found to be positive for PBV genogroup I. Sequence analysis further revealed the high genetic heterogeneity within representative PBV sequences. Additionally, both PBV-BCoV (n = 2) and BCoV-BRV-PBV (n = 1) co-infections were detected in bovine calves for the first time. Consequently, our findings pointed out the highly divergent nature of PBVs without regard to exact host or territory and the occasional co-existence with other enteric agents.

Survival of biological therapeutics in psoriasis: retrospective analysis of 3-years data in a Turkish registry, PSORTAKSIS.

BACKGROUND: TPSORTAKSIS is a psoriasis registry, which is used for follow-up of patients in Kayseri City Education and Research Hospital, Dermatology Clinic since 2016 in Turkey. PSORTAKSIS includes demographic data, follow-up clinical findings, laboratory output, and treatment information of patients. Here, drug survivals of biologic therapeutics (BT) according to three-year data of PSORTAKSIS will be presented. METHODS: Drug survival of BT in PSORTAKSIS was analyzed from 2016 to March 2019. RESULTS: 158 patients (111 of them BT-naive) with psoriasis under BT were enrolled in the current study. Drug survival analysis of patients with ongoing BT (158 treatment periods) revealed mean survival time as 15.49 months for ustekinumab, 15.37 months for adalimumab, 14.00 months for etanercept, 5 months for infliximab, and 4.59 months for secukinumab. The differences between drug survivals of BT were statistically significant (log-rank test, χ2 = 79.915, p < 0.0001).

Relationship between rosacea and chronic obstructive pulmonary disease: Rosacea and comorbidities: Rosacea and comorbidities.

BACKGROUND: Rosacea is a chronic inflammatory skin disease that has been reported to be associated with many systemic disorders including respiratory diseases. AIMS: This study aims to investigate respiratory function in patients with rosacea. PATIENTS/METHODS: Patients with rosacea and age- and gender-matched healthy volunteers were included in this cross-sectional study. Spirometric pulmonary function tests including the percentage of forced vital capacity (FVC%), percentage of forced expiratory volume in one second (FEV 1%), forced expiratory flow at 25-75% of FVC (FEF 25-75%), and FEV 1/FVC ratio was assessed in both patient and controls. The potential relationship between rosacea severity and pulmonary functions was assessed. RESULTS: A total of 120 patients with rosacea and 120 healthy controls were enrolled in the study. Compared to the controls, FEV 1%, FEV 1/FVC%, and FEF 25-75% values were significantly lower in patients with rosacea. Lower FEV 1/FVC% values were found to be associated with disease severity. FEV 1%, FEV 1/FVC%, and FEF 25-75% values were found to be more useful in differentiating the patients from healthy subjects. CONCLUSIONS: This study showed that patients with rosacea may have abnormal respiratory function compared to healthy subjects. Besides, disease severity was associated with worse respiratory functions. We believe that patients with rosacea, particularly those with additional risk factors, should be screened for respiratory disorders.

Food-dependent and food-exacerbated symptomatic dermographism: New variants of symptomatic dermographism.

BACKGROUND: Symptomatic dermographism (SD) is the most common form of chronic inducible urticaria. The criterion standard for diagnosing SD and disease activity assessment in SD is provocation testing. As of now, if and what cofactors have an impact on provocation test results is unknown. OBJECTIVE: We sought to determine whether the induction of signs and symptoms of SD is affected by the intake of food. METHODS: We performed standardized skin provocation testing with a dermographometer (FricTest) before and after the intake of food. Patients were off antihistamine treatment for at least 3 days before testing. In total, 17 patients were tested after not having eaten for at least 4 hours (preprandial) on one volar forearm and 60 minutes after a carbohydrate-rich meal (postprandial) on the other. FricTest responses (wheals, itch) at trigger thresholds were assessed at 5 and 30 seconds as well as at 1, 2, 5, and 10 minutes. RESULTS: We identified 7 patients with SD who showed faster onset of FricTest-induced whealing and/or lower trigger thresholds after the intake of food, that is, food-exacerbated SD. In 5 other patients, FricTest provocation testing resulted in a positive response only after the intake of food, but not before. Three of these 5 patients with food-dependent SD had comorbid chronic spontaneous urticaria and 1 had cholinergic urticaria. CONCLUSIONS: We describe 2 previously unknown subtypes of SD, food-exacerbated SD and food-dependent SD. The prevalence and underlying pathomechanisms of food-exacerbated SD and food-dependent SD need to be investigated, and the impact of food intake on other forms of chronic inducible urticaria should be explored.

The COVID-19 Pandemic Affects Male Patients With Chronic Spontaneous Urticaria More Than Female Patients.

Introduction: The COVID-19 pandemic dramatically disrupts health care for patients with chronic diseases including chronic spontaneous urticaria (CSU). As of now, it is unknown if the effects of the pandemic in CSU are different than in other chronic diseases. We also do not know, if different groups of CSU patients, for example female and male patients, are affected differently. Aim: To understand how CSU patients and subgroups are affected by the COVID-19 pandemic in their disease activity and control and treatment, using psoriasis as control. Patients and Methods: We analyzed 399 patients (450 visits) with CSU or psoriasis assessed during August 2019, i.e. before the pandemic, or August 2020, i.e. during the pandemic, for changes in disease activity, disease control, and the treatment they used, and how these changes are linked to age, gender, and disease duration. Results: Male but not female patients with CSU had markedly increased disease activity during the pandemic. CSU patients' age or disease duration were not linked to changes. Male and female patients with psoriasis showed similar increases in disease activity and decreases in disease control. The rate of omalizumab treatment, during the pandemic, was unchanged in male patients and increased in female patients with CSU. The efficacy of omalizumab treatment, during the pandemic, was reduced in male patients but not female patients with CSU. Conclusion: Male but not female CSU patients, during the COVID-19 pandemic, show loss of disease control linked to loss of omalizumab efficacy. The reasons for this need to be investigated.

Potential Utility of Oral Mucosal Capillaroscopy as an Indicator of Microvascular Damage in Behçet Disease: A Preliminary Study.

INTRODUCTION: Behçet disease (BD) is an auto-inflammatory condition characterized by multisystemic vasculitis. Oral mucosal capillaroscopy is an easy-to-use, repeatable, non-invasive method for evaluating mucosal microvasculature, contributing to the differential diagnosis and prognosis of various acute and chronic inflammatory diseases. OBJECTIVES: This study aims to characterize and describe the oral labial mucosal capillary findings in patients with BD using handheld dermatoscopy and to investigate the relationship between the capillary findings and the severity of the disease. METHODS: This cross-sectional study included patients with BD and healthy subjects. Capillaroscopic examination of the oral labial mucosa in each subject was performed by a handheld dermatoscope using polarized light. The clinical severity of BD was evaluated using Krause's Clinical Severity Scoring for BD. RESULTS: Sixty patients with BD and 60 healthy subjects were enrolled in the study. The frequencies of irregular capillaries, microhemorrhages, glomerular vessels, megacapillaries, and tortuous vessels were statistically significantly higher in the patient group when compared to the healthy individuals. In addition, a correlation was detected between the oral mucosal capillaroscopic findings and disease duration, severity, and vascular complications. CONCLUSIONS: Our study is the first to explore the potential role of oral mucosal capillaroscopic examination in patients with BD. Data obtained from this study indicated that oral mucosal capillaroscopy may be a useful tool to demonstrate microvascular damage in patients with BD.

Therapeutic efficacy and safety of three different modalities in pediatric patients with plantar warts.

Human papillomavirus infection is relatively common in communities. Thus, determining an effective and painless treatment method, especially in pediatric patients is of utmost importance. This study aimed to compare the outcomes of three different methods of treating plantar warts in pediatric patients. Children with verruca plantaris treated with a salicylic acid-lactic acid combination once daily (SA/LA 1), a salicylic acid-lactic acid combination applied in three to seven layers under occlusion every 3 days (SA/LA 2), or a combination of 5-fluorouracil (0.5%) and salicylic acid (10%) (SA/5-FU) were evaluated retrospectively. Treatment responses and recurrence rates were also evaluated after a minimum of 4 months. Among the 98 children with verruca plantaris, 19 were treated with SA/LA 1, 53 were treated with SA/LA 2, and 18 were treated with SA/5-FU; the eight patients who received cryotherapy were excluded. The mean treatment duration was significantly shorter in the SA/LA 2 group than in the SA/LA 1 group and the SA/5-FU group. (p = 0.000 for both) Application of a salicylic acid-lactic acid combination in multiple layers under occlusion is a safe, painless, and effective treatment method for plantar warts in children.

Molecular analysis of goose parvovirus field strains from a Derzsy's disease outbreak reveals local European-associated variants.

Since its first recognition in the early 1960s, Derzsy's disease has caused significant economic losses in the goose meat industry through the world. Today, Derzsy's disease still maintains its importance for small-scale waterfowl farming, despite not having a significant impact on public health. In the present study, we investigated the distribution of goose parvovirus (GPV) and its potential variants from a 2019 outbreak in Turkey. Tissue samples were obtained from infected eggs and goslings that were raised in distinct farming areas of the various provinces. For this purpose, a novel primer set for amplification of a 630-bp region of VP3 was designed to confirm GPV infection by conventional PCR method. A 4709-base nucleotide sequence including the structural, non-structural, and 5' inverted terminal repeat regions was obtained from three samples from the Central Anatolian region. Multiple sequence comparisons and phylogenetic analysis demonstrated that the field strains clustered with European group 2 and contained a series of unique amino acid substitutions that might affect the virulence of the virus. These results confirmed that European-related field strains caused the outbreak in Asia Minor, and this might assist in understanding the circulation of GPV in Asia and Europe.