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Little research on elder abuse was conducted in Japan until the Society for Study of Elder Abuse began its research in 1993. In two studies (1993, 1997), which surveyed social workers and home helpers, neglect was found to be the most common type of abuse, and daughters-in-law more often associated with neglect than spouses, sons, or daughters because of long term poor relationships. The research identified three reasons for the long term poor relationships and the factors that precipitated neglect and/or psychological abuse by daughters-in-law. [ABSTRACT FROM AUTHOR]

Abstract Background Ribosomal 5S genes are well known for the critical role they play in ribosome folding and functionality. These genes are thought to evolve in a concerted fashion, with high rates of homogenization of gene copies. However, the majority of previous analyses regarding the evolutionary process of rDNA repeats were conducted in invertebrates and plants. Studies have also been conducted on vertebrates, but these analyses were usually restricted to the 18S, 5.8S and 28S rRNA genes. The recent identification of divergent 5S rRNA gene paralogs in the genomes of elasmobranches and teleost fishes indicate that the eukaryotic 5S rRNA gene family has a more complex genomic organization than previously thought. The availability of new sequence data from lower vertebrates such as teleosts and elasmobranches enables an enhanced evolutionary characterization of 5S rDNA among vertebrates. Results We identified two variant classes of 5S rDNA sequences in the genomes of Potamotrygonidae stingrays, similar to the genomes of other vertebrates. One class of 5S rRNA genes was shared only by elasmobranches. A broad comparative survey among 100 vertebrate species suggests that the 5S rRNA gene variants in fishes originated from rounds of genome duplication. These variants were then maintained or eliminated by birth-and-death mechanisms, under intense purifying selection. Clustered multiple copies of 5S rDNA variants could have arisen due to unequal crossing over mechanisms. Simultaneously, the distinct genome clusters were independently homogenized, resulting in the maintenance of clusters of highly similar repeats through concerted evolution. Conclusions We believe that 5S rDNA molecular evolution in fish genomes is driven by a mixed mechanism that integrates birth-and-death and concerted evolution.

Background: Koalas, an Australian arboreal marsupial, depend on eucalypt tree leaves for their diet. They selectively consume only a few of the hundreds of available eucalypt species. Since the koala gut microbiome is essential for the digestion and detoxification of eucalypts, their individual differences in the gut microbiome may lead to variations in their eucalypt selection and eucalypt metabolic capacity. However, research focusing on the relationship between the gut microbiome and differences in food preferences is very limited. We aimed to determine whether individual and regional differences exist in the gut microbiome of koalas as well as the mechanism by which these differences influence eucalypt selection., Methods: Foraging data were collected from six koalas and a total of 62 feces were collected from 15 koalas of two zoos in Japan. The mitochondrial phylogenetic analysis was conducted to estimate the mitochondrial maternal origin of each koala. In addition, the 16S-based gut microbiome of 15 koalas was analyzed to determine the composition and diversity of each koala's gut microbiome. We used these data to investigate the relationship among mitochondrial maternal origin, gut microbiome and eucalypt diet selection., Results and Discussion: This research revealed that diversity and composition of the gut microbiome and that eucalypt diet selection of koalas differs among regions. We also revealed that the gut microbiome alpha diversity was correlated with foraging diversity in koalas. These individual and regional differences would result from vertical (maternal) transmission of the gut microbiome and represent an intraspecific variation in koala foraging strategies. Further, we demonstrated that certain gut bacteria were strongly correlated with both mitochondrial maternal origin and eucalypt foraging patterns. Bacteria found to be associated with mitochondrial maternal origin included bacteria involved in fiber digestion and degradation of secondary metabolites, such as the families Rikenellaceae and Synergistaceae. These bacteria may cause differences in metabolic capacity between individual and regional koalas and influence their eucalypt selection., Conclusion: We showed that the characteristics (composition and diversity) of the gut microbiome and eucalypt diet selection of koalas differ by individuals and regional origins as we expected. In addition, some gut bacteria that could influence eucalypt foraging of koalas showed the relationships with both mitochondrial maternal origin and eucalypt foraging pattern. These differences in the gut microbiome between regional origins may make a difference in eucalypt selection. Given the importance of the gut microbiome to koalas foraging on eucalypts and their strong symbiotic relationship, future studies should focus on the symbiotic relationship and coevolution between koalas and the gut microbiome to understand individual and regional differences in eucalypt diet selection by koalas., Competing Interests: The authors declare there are no competing interests., (©2024 Kondo et al.)

Early child maltreatment, such as child abuse and neglect, is well known to affect the development of social skills. However, the mechanisms by which such an adverse environment interrupts the development of social skills remain unelucidated. Identifying the period and brain regions that are susceptible to adverse environments can lead to appropriate developmental care later in life. We recently reported an excitatory/inhibitory imbalance and low activity during social behavior in the medial prefrontal cortex (mPFC) of the maternal separation (MS) animal model of early life neglect after maturation. Based on these results, in the present study, we investigated how MS disturbs factors related to excitatory and inhibitory neurons in the mPFC until the critical period of mPFC development. Additionally, we evaluated whether the effects of MS could be recovered in an enriched environment after MS exposure. Rat pups were separated from their dams on postnatal days (PDs) 2-20 (twice daily, 3 h each) and compared with the mother-reared control (MRC) group. Gene expression analysis revealed that various factors related to excitatory and inhibitory neurons were transiently disturbed in the mPFC during MS. A similar tendency was found in the sensory cortex; however, decreased parvalbumin (PV) expression persisted until PD 35 only in the mPFC. Moreover, the number of PV + interneurons decreased in the ventromedial prefrontal cortex (vmPFC) on PD 35 in the MS group. Additionally, perineural net formation surrounding PV + interneurons, which is an indicator of maturity and critical period closure, was unchanged, indicating that the decreased PV + interneurons were not simply attributable to developmental delay. This reduction of PV + interneurons improved to the level observed in the MRC group by the enriched environment from PD 21 after the MS period. These results suggest that an early adverse environment disturbs the development of the mPFC but that these abnormalities allow room for recovery depending on the subsequent environment. Considering that PV + interneurons in the mPFC play an important role in social skills such as empathy, an early rearing environment is likely a very important factor in the subsequent acquisition of social skills., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Irie, Ohta, Ujihara, Araki, Honda, Suzuki, Warita, Otabi, Kumei, Nakamura, Koyano, Miki and Kusaka.)

Epidemiological studies have indicated that child maltreatment, such as neglect, is a risk factor of escalated aggression, potentially leading to delinquency and violent crime in the future. However, little is known about the mechanisms by which an early adverse environment may later cause violent behavior. In this study, we aimed to thoroughly examine the association between aggression against conspecific animals and the activity of amygdala subnuclei using the maternal separation (MS) model, which is a common model of early life stress. In the MS group, pups of Sprague-Dawley rats were separated from their dam during postnatal days 2-20 (twice a day, 3 h each). We only included 9-week-old male offspring for each analysis and compared the MS group with the mother-reared control group; both groups were raised by the same dam during postnatal days 2-20. The results revealed that the MS group exhibited higher aggression and excessive activity of only the central amygdala (CeA) among the amygdala subnuclei during the aggressive behavior test. Moreover, a significant positive correlation was observed between higher aggression and CeA activation. While CeA activity is known to be involved in hunting behavior for prey, some previous studies have also indicated a relationship between CeA and intraspecific aggression. It remains unclear, however, whether excessive CeA activity directly induces intraspecific aggression. Therefore, we stimulated the CeA using optogenetics with 8-week-old rats to clarify the relationship between intraspecific aggression and CeA activity. Notably, CeA activation resulted in higher aggression, even when the opponent was a conspecific animal. In particular, bilateral CeA activation resulted in more severe displays of aggressive behavior than necessary, such as biting a surrendered opponent. These findings suggest that an adverse environment during early development intensifies aggression through excessive CeA activation, which can increase the risk of escalating to violent behavior in the future., (© 2023 International Society for Neurochemistry.)

Cellular senescence induces inflammation and is now considered one of the causes of organismal aging. Accumulating evidence indicates that age-related deterioration of mitochondrial function leads to an increase in reactive oxygen species (ROS) and DNA damage, which in turn causes cellular senescence. Thus, it is important to maintain mitochondrial function and suppress oxidative stress in order to inhibit the accumulation of senescent cells. Sesamin and its isomer episesamin are types of lignans found in sesame oil, and after being metabolized in the liver, their metabolites have been reported to exhibit antioxidant properties. However, their effects on cellular senescence remain unknown. In this study, the effects of sesamin, episesamin, and their metabolites SC1 and EC1-2 on replicative senescence were evaluated using human diploid lung fibroblasts, and TIG-3 cells. The results showed that sesamin and episesamin treatment had no effect on proliferative capacity compared to the untreated late passage group, whereas SC1 and EC1-2 treatment improved proliferative capacity and mitigated DNA damage of TIG-3 cells. Furthermore, other cellular senescence markers, such as senescence-associated secretory phenotype (SASP), mitochondria-derived ROS, and mitochondrial function (ROS/ATP ratio) were also reduced by SC1 and EC1-2 treatment. These results suggest that SC1 and EC1-2 can maintain proper mitochondrial function and suppress the induction of cellular senescence.

Cancer cells often respond to chemotherapeutic inhibitors by redirecting carbon flow in the central metabolism. To understand the metabolic redirections of inhibitor treatment on cancer cells, this study established a 13 C-metabolic flux analysis ( 13 C-MFA)-based method to evaluate metabolic redirection in MCF-7 breast cancer cells using mass spectrometry. A metabolic stationary state necessary for accurate 13 C-MFA was confirmed during an 8-24 h window using low-dose treatments of various metabolic inhibitors. Further 13 C-labeling experiments using [1- 13 C]glucose and [U- 13 C]glutamine, combined with gas chromatography-mass spectrometry (GC-MS) analysis of mass isotopomer distributions (MIDs), confirmed that an isotopic stationary state of intracellular metabolites was reached 24 h after treatment with paclitaxel (Taxol), an inhibitor of mitosis used for cancer treatment. Based on these metabolic and isotopic stationary states, metabolic flux distribution in the central metabolism of paclitaxel-treated MCF-7 cells was determined by 13 C-MFA. Finally, estimations of the 95% confidence intervals showed that tricarboxylic acid cycle metabolic flux increased after paclitaxel treatment. Conversely, anaerobic glycolysis metabolic flux decreased, revealing metabolic redirections by paclitaxel inhibition. The gap between total regeneration and consumption of ATP in paclitaxel-treated cells was also found to be 1.2 times greater than controls, suggesting ATP demand was increased by paclitaxel treatment, likely due to increased microtubule polymerization. These data confirm that 13 C-MFA can be used to investigate inhibitor-induced metabolic redirection in cancer cells. This will contribute to future pharmaceutical developments and understanding variable patient response to treatment.

This article indicates that capability building in the local community and accumulation of collaborative practice experiences gained at the local community level prove effective in actual disaster response and recovery. A case study of the Japanese community is introduced to illustrate this point. The article concludes with a discussion of the role and function of social workers in the context of such a community. In terms of disaster response and recovery, one of the essential roles of social workers is to encourage local people to empower other local people, organizations, and community.

In the present study, two alkaloids isolated from Pterogyne nitens, a plant native to Brazil, have been shown to induce apoptosis in human breast cancer cells. These compounds, pterogynine (PGN) and pterogynidine (PGD), were tested for their effect on a human infiltrating ductal carcinoma cell line (ZR-7531). The cell line was treated with each alkaloid at several concentrations. Time-dependence (with or without recuperation time) and concentration-dependence (in the range 0.25-10 mM) were investigated in cytotoxicity and apoptosis assays. The annexin assay indicated an apparently higher percentage of death by necrosis of malignant cells after 24 h exposure to both P. nitens extracts than the Hoechst assay. Thus, our results in the two tests demonstrated that the Hoechst assay can discriminate between late apoptotic cells and necrosis, whereas the flow cytometry-based annexin V assay cannot. We concluded that PGN and PGD have effective antineoplastic activity against human breast cancer cells in vitro, by inducing programmed cell death.

The carboxy-terminal domain (CTD) of the RNA polymerase II (Pol II) largest subunit undergoes reversible phosphorylation during transcription cycle. The phosphorylated CTD plays critical roles in coordinating transcription with chromatin modification and RNA processing by serving as a scaffold to recruit various proteins. Recently, we identified a novel human WW domain-containing protein PCIF1 as a phosphorylated CTD-interacting factor and demonstrated that PCIF1 negatively modulates Pol II activity in vivo. In the present study, to explore cellular functions of PCIF1, we generated PCIF1-deficient chicken DT40 cell lines. We observed significant up-regulation of WW domain-containing prolyl isomerase Pin1 in two independently established PCIF1-deficient mutant clones. As reconstitution of PCIF1 in the mutants did not reduce Pin1 expression, PCIF1 may not be a negative regulator of Pin1 expression. We assume that Pin1 over-expression might suppress defects caused by PCIF1 deficiency in DT40 cells. We furthermore compared PCIF1 and Pin1 for their functional properties and found that these two proteins exhibit most similar target specificity among other CTD-binding WW proteins, overlapping subcellular localization and comparative inhibitory effects on transcriptional activation by Pol II in human cultured cells. These results suggest that Pin1 may have overlapping cellular function with PCIF1 in vertebrate cells.

We evaluated the effects of a substrate in the biosynthesis of nitric oxide (NO)-l-arginine (LARG)-on hepatic lesions caused by ischemia/reperfusion (I/R) injury in rabbit livers. Rabbits were pretreated with LARG (150 mg/kg IV) or saline solution 0.9% (SS) before the hepatic I/R procedure. The effects of LARG on hepatic injury were evaluated before and after I/R. The warm hepatic I/R procedure produced profound acute liver injury, as indicated by elevated values of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH), as well as a high apoptotic cell count. All changes were attenuated by treatment with LARG before the hepatic I/R procedure. These results suggested that LARG produced protective effects on hepatic I/R lesions. This protective effect of LARG was probably associated with blocking generation of superoxide anions during the hepatic I/R procedure.

The Sexuality Study Group (chairperson: Chineko Araki) has researched the sexuality of middle-aged to elderly men and women who were having problems with their spouse, and suggestions for an improved sexual life. According to the result of the survey, the problem seemed to lie in the gap between men and women; men want sexual intercourse with women, while many women are satisfied with emotional affection. Discontinuance of intercourse is mainly caused by the loss of women's interest in sex. The responses to 'What kind of sexual relationship do you want to have with your spouse?' and other questions showed that whether women want to have sexual intercourse or not is not simply caused by a physical problem such as decrease of sexual desire or pain during intercourse, but is affected by various factors such as the affection to the spouse, physical and mental satisfaction by intercourse and a different way of thinking about sex. Also the survey showed even though both men and women wanted to have a 'casual conversation' or 'showing affection daily', in actual life they lacked having conversations and had little physical contact except for sex. For aging couples to keep matured sexual relations, it is more desirable to build the couples' relationship with casual conversation and physical contact, and also enjoy slow sex, such as pillow talk or caressing one another and not focusing on sex only.

Rheumatoid factor (RF) has been commonly used as a marker of rheumatoid arthritis (RA). RF can be detected in 60-80% of RA patients, but the specificity is low against other rheumatic diseases patients. We evaluated the diagnostic accuracy of anti-cyclic citrullinated peptide antibody (anti-CCP), a new diagnostic test for RA. Anti-CCP demonstrated higher sensitivity (81.0%) and specificity (92.4%). By the receiver operating characteristic (ROC) curve analysis, anti-CCP was superior to other markers (ie. RF, CARF, IgG-RF, and MMP-3). In early RA patients (RA patients who had had disease symptoms for < 2 years), sensitivity was 68.8%. Positivities of anti-CCP in RA patients became higher as the advance of stage defined by the Steinbrocker classification. We concluded that anti-CCP is a very valuable tool for the diagnosis of RA. Moreover, anti-CCP is a useful for finding RA of recent onset.

Purpose: We studied the efficacy of preoperative noninvasive assessment of the upper extremity to identify arteries and veins suitable for hemodialysis access to increase our use of autogenous fistulas (AF)., Methods: From Sep. 1, 1994, to Apr. 1, 1997, 172 patients who required chronic hemodialysis underwent segmental upper extremity Doppler pressures and duplex ultrasound with mapping of arteries and veins. The following criteria were necessary for satisfactory arterial inflow: absence of a pressure gradient between arms, patent palmar arch, and arterial lumen diameter 2.0 mm or more. The criteria necessary for satisfactory venous outflow were venous luminal diameter greater than or equal to 2.5 mm for AF and greater than or equal to 4.0 mm for synthetic bridging grafts (BG) and continuity with distal superficial veins in the arm. Intraoperative and duplex ultrasound measurements were compared. Contemporary experience was compared with the 2-year period (1992 to 1994) before implementation of the protocol., Results: During the period from Sep. 1, 1994, to Apr. 1, 1997, 108 patients (63%) had AF, 52 (30%) had prosthetic BG, and 12 (7%) had permanent catheters (PC) placed. Early failure was seen in 8.3% of AFs. Primary cumulative patency rates were 83% for AF and 74% for BG at 1 year (p < 0.05), with a mean clinical follow-up of 15.2 months. No postoperative infections were observed with AF, whereas six infections (12%) were observed with BG and two (17%) with PC insertion. During the period from June 1, 1992, to Aug. 31, 1994, 183 procedures were performed with a distribution of 14% AF, 62% BG, and 24% PC. In this earlier period the AF early failure rate was 36%, and the patency rates were 48%, 63%, and 48% for AF, BG, and PC, respectively (mean follow-up, 13.8 months)., Conclusion: A protocol of noninvasive assessment increased use of AFs. The cumulative patency rate of AFs was improved, and early failure rates were reduced when compared with the preceding institutional experience. Routine noninvasive assessment is recommended to document adequacy of arterial inflow and delineate venous outflow to maximize opportunities for AF.

Purpose: We describe a technique of superficial venous transposition in the forearm used for the formation of an arteriovenous fistula for hemodialysis access. These modifications of the single-incision radiocephalic fistula are designed to increase options for arteriovenous fistulas by using veins and arteries that are suitable for use but are not in immediate proximity., Methods: Arteries and veins suitable for a primary arteriovenous fistula were identified and mapped using duplex ultrasound in 89 patients. Separate incisions were used in the majority of cases, and the selected forearm vein was mobilized, angiodilated, and transposed into a subcutaneous tunnel on the volar aspect of the forearm. Before initiation of hemodialysis, duplex ultrasound scanning was performed, and the location that was most suitable for cannulation was identified. Repeat scans were performed at 3-month intervals for analysis of patency., Results: Superficial venous transpositions were performed using a single incision in 13 instances in which the vein was in immediate proximity to the radial artery (type A). Dorsal-to-volar forearm transposition (type B) was performed in 30 veins with anastomoses to the radial (n = 26), ulnar (n = 2), or brachial (n = 2) arteries. Volar-to-volar forearm transposition (type C) was performed in the remaining 46 veins, with anastomoses to the radial (n = 42), ulnar (n = 2), or brachial arteries (n = 2). Successful hemodialysis was accomplished in 81 of 89 patients (91%). The primary cumulative patency rate was 84% at 1 year and 69% at 2 years. The mean duration of follow-up was 14.3 months., Conclusions: The use of superficial venous transposition for the formation of autogenous hemoaccess was associated with ease of cannulation by dialysis personnel, high maturation rates, reduced early failure rates, and enhanced patency rates. We recommended the use of these technical modifications to increase the use of autogenous fistulas in the forearm.

Purpose: Vascular surgeons are ideally suited to select and perform endovascular interventions either as primary therapy or as an adjunct to bypass surgery. Attaining proficiency in endovascular techniques is an important goal in the training of vascular surgeons. We report our initial experience with a program of endovascular intervention performed in the operating room by vascular surgeons., Methods: During the previous three years, we performed 109 angioplasty procedures, 60 aortoiliac (55%), 32 femoropopliteal (29%), and 17 popliteal/tibial (16%), using guidewires and angioplasty balloons directed by intraoperative digital subtraction C-arm arteriography with road-mapping capabilities. Indications for angioplasty included disabling claudication in 59 patients (54%), rest pain in 18 (17%), and tissue loss in 32 (29%). Angioplasty was accompanied by stent placement in 39 of 60 aortoiliac procedures (65%) and in two of 32 femoral procedures (6%). In 16 cases (15%), the endovascular procedure was performed in conjunction with a bypass procedure. In selected cases (15, 14%), duplex scanning was the sole diagnostic method used before surgery to identify the lesion, eliminating the need for preoperative arteriographic scans. Segmental pressure measurements, duplex ultrasound scans, and treadmill exercise testing as indicated were performed before and after surgery. The efficacy of the endovascular intervention was assessed at 3-month intervals during the first year and at 6-month intervals thereafter., Results: A successful results was defined using criteria recommended by the Ad Hoc Subcommittee on Reporting Standards for Endovascular Procedures from the Society for Vascular Surgery/International Society for Cardiovascular Surgery. This included the combination of symptomatic improvement, obtaining an anatomically successful result with < 30% residual lumen stenosis, and elimination of the translesion gradient with an improvement in high thigh-brachial index or ankle-brachial index greater than 0.15. Initial success was achieved in 55 of 60 aortoiliac (92%), 28 of 32 femoropopliteal (88%), and 16 of 17 popliteal/tibial (94%) angioplasty procedures. Clinical follow-up has been achieved in all cases, with continued clinical success rates of 80%, 75%, and 82% for aortoiliac, femoropopliteal, and popliteal/tibial angioplasty procedures, respectively, with a mean follow-up of 15.7 months., Conclusion: These results confirm the value of a program in which C-arm technology was used by vascular surgeons in the performance of angioplasty and stenting procedures in the operating room. This experience in therapeutic endovascular intervention will facilitate the credentialing process for future vascular surgeons.

Purpose: This study was undertaken to determine the degree of clinical and hemodynamic improvement after surgical ablation of incompetent superficial and perforator veins in limbs with combined deep and superficial venous incompetence manifested by chronic dermal ulceration., Methods: Eleven limbs in 10 patients with class 5 or 6 venous insufficiency (ulceration) were assessed by CEAP (clinical, etiologic, anatomic, pathophysiologic) clinical scores, air plethysmography, color duplex ultrasonography, and phlebography (both ascending and descending). Surgical ablation of superficial and perforating veins was performed, followed by repeat clinical, air plethysmographic, and color duplex ultrasonographic examinations., Results: All 11 limbs had combined deep and superficial vein reflux on the preoperative color duplex ultrasound scan. Clinical symptom scores decreased from 10 to 1.4 after operation. Postoperative air plethysmography demonstrated significant reduction in reflux as measured by the mean venous filling index, which decreased from 12 +/- 5 ml/sec to 2.7 +/- 1 ml/sec after surgery. Calf pump function was also significantly improved, with a mean ejection fraction that increased from 43% +/- 11 to 59% +/- 13 and mean residual volume fraction that decreased from 56% +/- 15 to 33% +/- 16. Each of these measures was significantly different from the preoperative value (p < 0.05). Similar improvement characterized subgroups of limbs with three or more incompetent deep segments (n = 6) or popliteal segment incompetence (n = 6)., Conclusions: Superficial and perforating vein incompetence accounts for a substantial and correctable component of venous insufficiency in limbs with combined deep and superficial vein reflux and venous ulceration. These data indicate that surgical correction of this component significantly improves clinical symptoms and venous hemodynamics. Superficial and perforator ablation is an appropriate initial step in the management of combined deep and superficial venous incompetence.

Purpose: Calf muscle pump dysfunction is a recognized factor in chronic venous insufficiency (CVI). We investigated the hypothesis that limbs with CVI have a reduced ankle range of motion (ROM) that may be responsible for the poor calf pump function associated with venous ulceration., Methods: Ankle ROM and calf pump function were assessed in 32 limbs of 26 adult men. Limbs were selected on the basis of clinical presentation: normal (n = 6 limbs), class 1 or 2 CVI with no history of ulceration (n = 9 limbs), class 3 CVI with healed ulceration (n = 9 limbs), and class 3 CVI with active ulceration (n = 8 limbs). ROM was determined by goniometry during maximal plantar flexion and dorsiflexion of the ankle. Calf pump function was determined by air plethysmographic measurement of ejection fraction (EF) and residual volume fraction (RVF)., Results: Ankle ROM was significantly (p < 0.05) reduced in each CVI group compared with age-matched control subjects, because of decreases in both plantar flexion and dorsiflexion. Calf pump function was significantly impaired (decreased EF and increased RVF) in ulcerated limbs. ROM was significantly correlated to EF and RVF. Impairment of ROM and calf pump function was associated with deterioration in the clinical classification of venous disease., Conclusions: Limbs with CVI have a limited ankle ROM that decreases with increasing severity of clinical symptoms. This decreased ROM is associated with, and may contribute to, poor calf pump function.