Uterine arteriovenous malformation (AVM) is associated with a risk of massive uterine bleeding. Although uterine artery embolization remains the first-line treatment for AVM, there has been a recent exploration of pharmacological options. Danazol is known to reduce blood flow to the uterus; however, our understanding of its therapeutic efficacy for AVM remains limited. Herein, we present the results of danazol use in patients with uterine AVM. We retrospectively reviewed the medical records of patients who received danazol for the treatment of AVM between January 2013 and November 2022. The cohort comprised 10 patients who developed AVM after dilatation and curettage (D&C), abortion, or cesarean section. Danazol was administered twice daily at a total dose of 400 mg/day, and was employed for AVM treatment in hemodynamically stable patients who provided consent and were devoid of massive bleeding. Outpatient follow-ups (ultrasound measurements of AVM size and symptom assessment) were performed every 2 weeks. AVM was successfully treated with danazol in most patients with no adverse event. Eight postabortal patients had complete resolution of AVM after an average of 45 days (range 14–70 days). Of two patients who developed AVM after a cesarean section, one experienced AVM reduction, and the other developed massive bleeding, requiring emergency uterine artery embolization. In light of these outcomes, danazol can be potentially prioritized over uterine artery embolization in the treatment of AVM after abortion in hemodynamically stable patients. Uterine arteriovenous malformation (AVM) is a vascular structural anomaly caused by abnormal connections between the uterine arteries and veins that bypass the capillary system in the uterine myometrium. Despite its rarity, AVM can be life-threatening due to the risk of massive uterine bleeding ,2,3. WhiSymptoms of AVM include menorrhagia, abnormal/irregular bleeding, anemia, and lower abdominal pain. As massive bleeding can induce hemodynamic instability, emergency hysterectomy may be considered in severe cases ,8. HowevIn the past, AVM was pathologically diagnosed following hysterectomy in most cases. Currently, various techniques such as contrast-enhanced computed tomography, hysteroscopy, angiography, and magnetic resonance imaging are used for the diagnosis of AVM. Recently, vaginal sonography combined with color Doppler imaging has emerged as the preferred initial choice of diagnostic method due to its benefits of being rapid, simple, cost-effective, and noninvasive. This technique allows visualization of grayscale cystic lesions and tubular anechoic spaces within the myometrium, coupled with the identification of turbulent hypervascular flow via Doppler imaging ,10.There is a scarcity of data concerning the optimal management of AVM; historically, uterine artery embolization (UAE) is commonly regarded as a first-line treatment ,12. A keDanazol, an isoxazole derivative of 17-alpha-ethinyl testosterone, has previously been used to treat dysfunctional uterine bleeding or heavy menstrual bleeding. Although the exact mechanism of action is not known, it is thought to be effective in reducing uterine artery blood flow . To dateIn this retrospective study conducted from January 2013 to November 2022, we enrolled 10 patients to receive danazol for the treatment of AVM at Kangnam Sacred Heart Hospital. This study received approval from the Institutional Review Board , which waived the requirement for informed consent. AVM was diagnosed by transvaginal sonography with color Doppler imaging based on the presence of hypoechoic or tubular anechoic areas within the myometrium, with abundant high flow rates and low resistance on color Doppler imaging. To eliminate the possibility of vasculogenesis associated with gestational trophoblastic disease, the serum human chorionic gonadotrophin (hCG) levels of patients were evaluated before treatment. Patients with serum hCG levels of ≥30 mUI/mL were monitored to confirm a decrease in these levels.Among the available pharmacological choices, danazol was selected due to its established use in managing menorrhagia and its effectiveness in decreasing uterine blood flow . MoreoveDanazol administration was considered as a treatment option for AVMs with a maximum diameter of <5 cm in hemodynamically stable patients without massive bleeding, whereas UAE was preferably performed in patients with massive bleeding or those with hemodynamic instability. In addition, factors such as future pregnancy plans and patient compliance were taken into consideration, as consistent medication and regular hospital visits are crucial aspects of pharmacological treatment. Adequate information was provided to the patients on the possibility of treatment failure, including the possibility of emergency UAE or hysterectomy owing to significant bleeding during treatment or treatment failure, and the use of other available medical treatments other than danazol. Patients were thoroughly informed about the potential adverse effects of danazol such as weight gain, acne, voice change caused by the androgen effect, and menopause-like symptoms including hot flashes and vaginal dryness . DanazolIn total, danazol therapy was initiated in 16 patients who received sufficient explanation. Of these 16 patients, 6 were lost during the follow-up period. Thus, we analyzed the treatment progress of the remaining 10 patients who successfully completed the prescribed treatment. These patients were instructed to undergo regular outpatient follow-ups every 2 weeks for ultrasound measurements of AVM size, assessments of symptoms such as vaginal bleeding, and to check signs of adverse effects of danazol. The decision to continue with danazol therapy was based on these findings. Danazol therapy was discontinued once symptoms of vaginal bleeding were resolved and ultrasound examinations confirmed the absence of visible flow and revealed normal appearance in both the endometrium and myometrium.Seven of the ten analyzed patients had developed AVM after D&C for abortion, one patient had developed AVM after complete abortion, and two had developed AVM following cesarean section. Detailed clinical characteristics of these patients are presented in Ultrasound findings revealed complete resolution of AVM following danazol treatment in eight patients, all of whom developed AVM after abortion (either D&C or complete abortion). All eight of these patients experienced a return to normal menstruation within 2 months after completion of danazol treatment . In one patient who underwent cesarean section due to monochorionic twin pregnancy at 36 weeks, although blood flow in the AVM disappeared on ultrasound after using danazol for 35 days, a 3.1 × 1.0 cm hyperechogenic lesion was observed around the endometrium. Danazol administration was discontinued since the absence of any AVM symptoms such as vaginal bleeding. During the 6-month follow-up, the size of the hyperechogenic lesion decreased to <1 cm and the patient had normal menstruation without any abnormal symptoms, resulting in follow-up loss during the observation period without further treatment. Another patient had undergone a cesarean section at 37 weeks due to placenta previa totalis. Accompanied by placenta accreta, the placenta was delivered with difficulty during surgery. This patient was diagnosed with AVM on the 24th day after surgery, and during danazol treatment, significant vaginal bleeding continued; thus, UAE was performed on day 21 of danazol treatment. None of the other patients developed massive hemorrhage during danazol treatment, and the volume of bleeding tended to drop over the duration of danazol therapy, eventually ceasing altogether. In addition, no patients developed adverse effects related to danazol.Although there are several therapeutic options for uterine AVM, UAE is generally considered the first-line treatment. However, UAE may not be the optimal treatment for women of childbearing age, as it is costly, invasive, may not be universally available, and carries concerns regarding future fertility associated with post-procedural intrauterine adhesions or ovarian insufficiency. In contrast, pharmacological treatments have the advantages of being less expensive, easier to access, less invasive, and not likely to affect future fertility. However, pharmacological treatment can only be applied to patients who are hemodynamically stable and do not have a massive hemorrhage. As many cases of AVM are detected early owing to advances in and increased access to ultrasound, most recent patients are hemodynamically stable without massive bleeding at the time of diagnosis. As such, the number of patients to which the pharmacological approach can apply is increasing.Pharmacological treatments that have been reported for AVM include GnRH agonists, progestins, danazol, uterotonics, methotrexate, and combinations of these drugs ,18,19,20Vilos et al. showed that the combination of a GnRH agonist with a transient aromatase inhibitor and tranexamic acid was effective in both treating and preserving reproductive capabilities in women with AVMs accompanied by abnormal uterine bleeding . DespiteAlso, as these success rates mentioned above are mainly based on case reports or case series of successful outcomes, this success rate may not be accurate, and comparisons cannot be made with the success rate of UAE. In addition, as AVM is rare and there is consequently a lack of data, it is difficult to identify the factors related to treatment success because of the significant heterogeneity of patient characteristics and pharmacological treatment regimen and doses.This study reported the experience of using one drug in a relatively large number of patients with AVM treated in a single center. In the present study, AVMs completely resolved in 8 of 10 patients prescribed danazol. In one patient, the AVM did not completely resolve but significantly decreased in size, and the residual AVM did not trigger any events during the follow-up period of seven months after medication administration. One other patient developed a significant hemorrhage after 21 days of danazol treatment, necessitating UAE. In both cases of incomplete resolution, patients developed AVMs after undergoing a cesarean section, indicating that danazol could be less effective in patients who have had a cesarean section. The strength of this study lies in its relatively large number of patients with AVM and its finding that danazol was effective in postabortal patients. However, this study has some limitations. First, it lacks a control group, such as one using alternative pharmacological treatments, or an expectant management. Thus, the superior efficacy of danazol for AVM treatment could not be evaluated through group comparisons. Second, the diagnosis of AVM was solely based on the presence of a distinct vascular network within the myometrium observed on vaginal sonography combined with color Doppler without using other diagnostic methods such as computed tomography, hysteroscopy, or magnetic resonance imaging, which may be insufficient for diagnosing AVM. Given these limitations, it is essential to incorporate a well-designed control group utilizing a wider range of diagnostic methods in future studies to reveal the effectiveness of danazol in the treatment of AVM.The study findings suggest that for the treatment of AVM occurring after D&C or abortion in hemodynamically stable patients without significant massive bleeding, danazol can be preferably administered before considering UAE. Among the ten patients included in this study, eight showed complete resolution of AVM. However, patients must be adequately informed of the possibility of treatment failure and risks of massive bleeding during danazol use before initiating medication. In addition, danazol treatment must be attempted only in patients who display good treatment adherence and are capable of undergoing careful follow-up. Although the results of this study cannot conclude the treatment efficacy of danazol on AVM treatment, they contribute to the growing evidence in the literature of its efficacy and help clinicians in deciding treatment options for AVM.


N = 702 pregnant women and their male partners (n = 351 couples) were recruited and enrolled. Couples were assessed twice pre-birth, 2 weeks post birth, and 6 months post birth. Expectant mothers were an average of 15.05 weeks pregnant (SD = 8.83). Thirty-nine pregnancies did not result in a live birth (11%), 14 couples withdrew from the study or were lost to follow-up prior to delivery (4%), and 148 babies were born female (42%), leaving 150 couples with a male infant in the analytic sample (43%). The LFLS study achieved significantly higher EIMC rates (35%) in comparison with previously observed EIMC study rates in Zambia (11%), and significantly higher than hypothetical comparison rates up to 30%. Relative to baseline rates, odds of VMMC among couples’ older sons increased by 31% at post-intervention and by 90% at two-weeks following birth. Overall, this pilot study found the LFLS intervention to be feasible, acceptable, and effective in doubling the rate of EIMC in comparison with a previous longitudinal study in Zambia. Future research should consider a family-centric approach to promotion of male circumcision for infants and adolescents. LFLS may be effective in promoting father-son “bonding” by MC status; a bond that may be a bridge to increase both EIMC and VMMC uptake in newborns and couples’ older sons and is a novel leverage point for promotion of this HIV prevention strategy.Voluntary Medical Male Circumcision (VMMC) is an effective strategy for HIV prevention in areas with high prevalence of, and risk for, HIV. More than 361,000 male neonates are born each year in Zambia, many of whom could be eligible for Early-Infant Medical Circumcision (EIMC). Building on successful implementation strategies utilized in our Spear & Shield program, this pilot study, “Like Father, Like Son” (LFLS), evaluated the feasibility and acceptability of offering combined EIMC and VMMC services and couple-level behavioral interventions. A total of  Voluntary Medical Male Circumcision (VMMC) is an effective strategy for HIV prevention in areas with high HIV prevalence –3 and thUpwards of 360,000 of male neonates eligible for Early-Infant Medical Circumcision (EIMC) are born each year in Zambia. The timing for male circumcision is crucial, and integration of circumcision during the neonatal period was proposed by the Government of Zambia Ministry of Health (GZMOH) in 2008 due to both practical and medical considerations . Early-IApproximately 60% of expecting Zambian parents expressed concerns regarding EIMC, such as fragility of the neonate penis, quality of the EIMC, and post-procedural care . And whiThis pilot study, entitled “Like Father, Like Son” (LFLS), evaluated the feasibility and acceptability of offering combined EIMC and VMMC services and behavioral interventions, building on successful implementation strategies utilized in S&S. It was theorized that the LFLS program could be a viable strategy to increase acceptability and uptake of EIMC among hesitant expecting parents. This study sought to determine whether father-son “bonding” by MC status would increase both VMMC and EIMC uptake in newborns, couples’ older sons, and fathers compared to historical EIMC and VMMC rates in Zambia.Prior to study initiation, ethical approval was obtained from the University of Miami Institutional Review Board, the University of Zambia Biomedical Research Ethics Committee, and the Zambian National Health Research Authority. All procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation  following the Helsinki Declaration of 1975, as revised in 2000. All participants provided written informed consent to participate in the study at enrollment. The LFLS protocol was registered on clinicaltrials.gov under trial number NCT04119414.N = 702 pregnant women and their male partners (n = 351 couples) were recruited and enrolled in Zambia from June 2019 to June 2022. Expecting mothers were an average of 15.05 weeks pregnant (SD = 8.83). Thirty-nine pregnancies did not end in a live birth (11%), 14 couples withdrew from the study or were lost to follow-up prior to delivery (4%), and 148 babies were born female (42%), leaving 150 couples with a male infant in the analytic sample (43%). The study timeline is described in A total of Following screening and consent, a baseline audio computer-assisted self-interview (ACASI) assessment was conducted in English, Nyanja, or Bemba  in private study offices. Study staff demonstrated how to use the ACASI system and were available to assist participants and respond to queries regarding the assessment.The LFLS study was conducted in four urban community health centers (CHCs) in Lusaka District, Zambia. CHCs were selected based on catchment area ≥30,000; 2 healthcare providers for EIMC training and provision, 2 Voluntary Counseling and Testing (VCT) counselors and Antenatal care (ANC) staff available to offer an intervention, ≥150 births per month, a maternity ward, and dedicated space for both MC (EIMC and VMMC) procedures.Participants’ demographic characteristics assessed included age, employment, religious affiliation, personal yearly income, education, marital status, pregnancy status, and whether they had their own children or were raising others’ children. Participants also provided information on both parents’ HIV status.Sites received S&S+LFLS training. The CHCs selected 2 VCT/ANC counselors/staff  to receive training to conduct the S&S+LFLS intervention. S&S training commenced with a 2 day intensive review of the S&S program manual followed by supervised “on the job” training sessions with a S&S staff trainer. The trainees participated in three 4 session S&S groups and five 2 session LFLS couple interventions. The first S&S/LFLS group and couple sessions were led by a study staff member with trainee(s) observing; second and third group sessions were co-led by trainee and study staff; fourth S&S session were led by trainee, with study staff observing. A similar pattern took place with the couple sessions. Following completion of the S&S+LFLS training, study staff reviewed trainee’s performance for both interventions and recommended certification, or additional training on either or both interventions. As EIMC decision making has been linked to mother’s HIV status, the LFLS couples component included elements from the couples’ voluntary HIV testing and counseling (CVCT), which applies a solution-focused model to avoid blame and instead centers on present and future behavior based on the CVCT Curriculum , 22. TheThe S&S VMMC intervention applied the Information Motivation Behavioral Skills (IMB) model to promote VMMC, providing VMMC related-information, increasing motivation to undergo VMMC, and promoting VMMC uptake and skills to reduce HIV risk and improve hygiene . VMMC inThe LFLS EIMC intervention for parents also applied the Information Motivation Behavioral Skills (IMB) model to promote EIMC  . The intThe proposed EIMC pilot study was also guided by the theories of reasoned action  members contributed to LFLS sessions in focus group discussions. Content was pertinent to the cultural, social and religious issues and beliefs influencing EIMC decision making, and included previous Zambian research on this topic , 17.Session 1 focused on the immediate benefits associated with EIMC: Cost effective, faster wound healing, easier to circumcise, less chance of adverse events, easier to clean the penis, reduced urinary tract infections. Masculine cultural norms related to potential pain, sexual performance, and pleasure were addressed during the S&S program; couples learned that potential pain is diminished if the procedure is completed during infancy. Pregnancy heightens awareness of danger and safety for the infant, and the desire to protect the infant. Couples were encouraged to weigh both present and future benefits and risks for the male child, utilizing a cost/benefit approach that incorporates cultural norms regarding the health and wellbeing of all family members. Session 1 included a testimonial from a medical practitioner with EIMC experience, and at the end of the session, couples were invited to return to Session 2 with an influential other, if desired. EIMC brochures were distributed.Topics included: Why undergo EIMC? What are the benefits? Why now? When is the best time for EIMC? Information: What happens? How long does it take? Is it painful, how is pain controlled? What happens next? How long is healing, cleaning during healing? What happens to the foreskin? What are the risks? Is it safe? Who should be involved in the decision? Any additional questions or concerns about EIMC? The feasibility and acceptability of LFLS was assessed by assessing participants about the utility of each of these topics during their last assessment (see Table 2).The PI, Co-PIs, consultants, and study staff trained CHC staff in study protocols, including recruitment and intervention procedures. The US and Zambia teams held biweekly calls to review the study progress. Semi-annual visits were made by members of the US team for protocol review, ongoing process monitoring and quality assurance; process evaluation is used to ensure fidelity to the study protocol. All LFLS sessions were recorded; 1) 10% of recordings were randomly reviewed and rated for fidelity by the Project Coordinator, and 2) feedback provided to the counselor within one week of the review; 3) all reviewed recordings would be entered in a spreadsheet detailing completed intervention components that 4) were reviewed by the US Co-PI (Jones); 5) the Project Director and the US PI discussed the reviews to resolve fidelity issues collaboratively. ACASI assessment quality assurance were conducted by US data manager biweekly. Quarterly meetings of CHC and S&S staff were held to encourage team members to review study issues and discuss and resolve difficulties in a timely manner.p value of .2 in bivariate tests were included in the model. Changes in father and other son(s)  VMMC status and plans to undergo circumcision following Spear & Shield were analyzed using mixed effects logistic regression. Time (pre- vs. post-intervenion) was the predictor of interest and random intercepts were estimated for fathers (for father VMMC status) or subjects within couples (for other son(s) VMMC status). Finally, EMIC decision making data were summarized among the couples who elected to have their newborn circumcised. All statistical analyses were conducted using R v.4.2.1.Participant characteristics were summarized using descriptive statistics and compared between couples electing EMIC vs. those not circumcising their newborns using chi-square tests. Data were collected from both couple members; where there were high levels of agreement  men’s responses have been reported. As there was no control group in this pilot study, the proportion of couples electing EMIC was compared to an estimated historical rate of 11%  as well N = 150 couples delivering a male infant. Demographic characteristics of male and female members of each couple, overall and split by EMIC status, are presented in SD = 6) years of age, overall, while women were 26 (SD = 5). More men were employed (83%) than their female partners (33%), although rates of higher education (more than primary school) were similar (~70% for both men and women). Most couples (72%) reported a household income of less than 5,000 Zambian Kwacha ($245 USD) per month, which is on parr with the average Zambian household income of $211 USD. Eighty-seven percent of men and 90% of women reported being married, 76% reported living with their spouse or partner, and two-thirds of each gender reported having other children. Eight percent of men and 14% of women reported HIV-positive serostatus. Ninety-one percent of couples received the LFLS and S&S intervention sessions. Importantly, no adverse events were reported by any of the participating couples, for the male partner and all their sons. Participants’ responses to the feasibility and acceptability of LFLS, assessed by assessing participants about the utility of each of the topics covered during sessions, are presented in Participants were p < .001;  and 90% at two-weeks following birth, relative to baseline .At baseline, fifty-nine percent of fathers reported being circumcised  were more likely than men (24%) to have consulted their mother prior to deciding to circumcise, but there was little difference between men and women in terms of consulting their fathers . In addition to parents, couples were likely to have discussed circumcision with friends (48% of women and 37% of men). Proportions of participants consulting grandmothers, sisters, uncles, or aunts were generally in the 15–30% range. Across all persons consulted, participants were advised that circumcision was a good idea 80–90% of the time, with grandmothers least likely to be supportive (67% supported EIMC).This feasibility study assessed the potential for the LFLS intervention to promote EIMC uptake above EIMC rates previously observed in Zambia, building on the successful implementation and dissemination of the S&S intervention across a series of studies , 43. In Findings from this study were promising and suggest that LFLS was successful in increasing EIMC rates as well as older sons’ VMMC status. About ~361,000 male babies are born each year in Zambia, most of whom would be candidates for EIMC, and substantial research has already been conducted on factors related to parents’ decisions to circumcise their sons , 44–47. despite its higher risks compared to EIMC.Despite the promising findings in favor of EIMC rates and other sons’ VMMC rates from this study, fathers’ VMMC status were not affected by the intervention. This finding may be related to the emphasis of the intervention on the benefits of, and lower risks associated with EIMC compared to adults’ VMMC. Indeed, research suggests that the neonatal period is the ideal time for male circumcision to be performed. In a 2012 review, the American Academy of Pediatrics concluded that health benefits of newborn circumcision not only outweigh the risks, but also justify being accessible to all families that choose this option . Long-teWe examined demographic and other participant characteristics in relation to EIMC. No baseline demographic or other participant characteristics were significantly predictive of EIMC. Previous studies have assessed parents’ attitudes towards EIMC . Noted aThis study makes an important contribution to the literature on EIMC, but it is not without limitations. First, the LFLS intervention was conducted in four urban community health centers in Lusaka District, Zambia. As our previous studies have shown, the implementation and dissemination of S&S carried unique challenges at each province during implementation , 42, 51.This pilot study found the Like Father Like Son intervention to be feasible, acceptable, and effective in doubling the rate of EIMC in comparison with a previous Zambian study. Future research should consider a family-centric approach to promotion of male circumcision for infants and adolescents. LFLS during the perinatal period may be effective in promoting both VMMC in sons and EIMC in neonates which may create a novel leverage point for promotion of this HIV prevention strategy.S1 File(PDF)Click here for additional data file.S2 File(CSV)Click here for additional data file.


Previously thought to be congenital, AVMs have shown evidence of de-novo formation and continued growth, thus shifting thoughts on their pathophysiology. Pediatric AVM patients have been reported to be more prone to develop AVM recurrence after a seemingly complete cure. Therefore, we assessed the risk of AVM treated in childhood to recur in adulthood after a long-term follow-up in our own cohort.Control DS-angiography was arranged during 2021–2022 as part of a new protocol for all AVM patients who were under 21 years of age at the time of their treatment and in whom the treatment had occurred at least five years earlier. Angiography was offered only to patients under 50 years of age at the time of the new protocol. The complete eradication of AVM after the primary treatment had been originally confirmed with DSA in every patient.A total of 42 patients participated in the late DSA control, and 41 of them were included in this analysis after excluding the patient diagnosed with HHT. The median age at the time of admission for AVM treatment was 14.6  years. The median age at the time of the late follow-up DSA was 33.8 years . Two recurrent sporadic AVMs and one recurrent AVM in a patient with hereditary hemorrhagic telangiectasia (HHT) were detected. The recurrence rate was 4.9% for sporadic AVMs and 7.1% if HHT-AVM was included. All the recurrent AVMs had originally bled and been treated microsurgically. The patients with sporadic AVM recurrence had been smoking their whole adult lives.Pediatric and adolescent patients are prone to develop recurrent AVMs, even after complete AVM obliteration verified by angiography. Therefore, imaging follow-up is recommended. The leading cause of hemorrhagic stroke in the pediatric population is a ruptured brain arteriovenous malformation (AVM) . FurtherOnce complete eradication or occlusion of AVM has been verified by digital subtraction angiography (DSA), no further long-term angiographic follow-up has been generally warranted in adult patients. However, there is diversity in the guidance on following pediatric patients after successful AVM treatment. Some studies suggest that the first angiographic follow-up with magnetic resonance angiography (MRA)  or with In this study, we aimed to assess the risk of late AVM recurrence in patients treated during childhood or early adulthood that displayed complete eradication or occlusion after the initial treatments. We conducted the long-term follow-up with DSA as the sensitivity of MRA may not always be sufficient in detecting small recurrent brain AVMs . We hypoWe retrospectively collected data on pediatric AVM patients admitted to the Department of Neurosurgery, Helsinki University Hospital , during 1985–2012. Traditionally, we have not conducted routine long-term follow-up angiographic imaging in asymptomatic patients with AVMs in which complete eradication was verified by DSA. On the basis of increasing clinical experience of recurrences, however, we introduced a follow-up protocol in January 2021 comprising a clinical visit and DSA study for patients treated in childhood or early adulthood (<21 years) to evaluate the long-term risk of AVM recurrence. The control DSA study was offered to patients under 50 years of age at the time of follow-up, as possible asymptomatic recurrences would probably not have led to any interventions in those older than 50 years.We did not include extracranial AVMs; thus, the abbreviation “AVM” in this study refers only to brain AVMs. All AVM diagnoses were confirmed by digital subtraction angiography (DSA). AVM size, location, angioarchitecture, and associated aneurysms were evaluated from DSA and, if relevant, from computer tomography angiography (CTA) and magnetic resonance images (MRI). We scrutinized the patients’ medical records, including relevant radiological images . All patients had a post-treatment DSA after the last treatments that confirmed complete AVM eradication or occlusion.Patients fulfilling the new follow-up protocol criteria were contacted by letter and offered a clinical follow-up visit, followed by a DSA study if the patient gave consent after counseling. All patients that underwent DSA had a complete four-vessel DSA study  and bilateral vertebral artery (VA) and, if deemed necessary, separate internal carotid artery (ICA) and external carotid artery (ECA) angiographies. An experienced neuroradiologist and neurosurgeon independently analyzed all DSA studies.Due to the relatively small number of patients, we did not conduct any statistical intergroup comparisons. We present categorical variables as absolute numbers with percentages. We analyzed continuous data for skewness, and since all data were non-parametrically distributed, we present continuous data as medians with interquartile ranges and minimum and maximum ranges. We performed the statistical analysis using SPSS software version 24.0 . One patient with an HHT-related AVM is presented separately and excluded from the analyses.Of 54 patients treated for AVM under the age of 21, 47 had a completely occluded or eradicated AVM. Of these 47 invited patients, three could not be reached, and two declined to participate in the DSA study. A total of 42 patients participated in the late DSA control, and 41 of them were included in this analysis after excluding the patient diagnosed with HHT (who is presented separately) . Three out of 42 patients demonstrated AVM recurrence at follow-up DSA, of which one was HHT-related AVM (4.9% recurrence rate for sporadic AVMs and 7.1% for the entire 42-patient cohort including the HHT-related AVM). Of the two patients with a recurrent AVM (excluding the HHT patient), the initial Spetzler-Martin grades were II and III, and both AVMs had bled before the obliteration. Both patients were male and active smokers. Both sporadic AVM recurrences in our study were also seen in MRI + 3D time-of-flight (TOF)-MRA performed after the DSAs. HHT-related small recurrent AVM was not observable in the MRI + 3D TOF-MRA imaging performed 15 months before the DSA.The median size of AVM nidus (in greatest dimension) was 29 mm , 14 patients (34%) received multimodality treatment, one patient 2%) was treated only with radiotherapy, and two patients (5%) were treated only with endovascular embolization. The treatment modalities are presented in greater detail and in comparison with recurrent AVMs in Table % was treA previously healthy 19-year-old man doing his military service experienced a sudden headache in the morning. The CT scan revealed an intracerebral hemorrhage (ICH) in the left temporal lobe. The patient was referred to the neurosurgical department. No neurological defects were observed, and the Glasgow Coma Scale (GCS) was 15. The DSA study demonstrated a somewhat diffuse left-sided temporal AVM with a maximum diameter of 2.5 cm. AVM received arterial feeding from the left posterior cerebral artery (PCA) and the left middle cerebral artery (MCA) and drained to the transverse sinus and straight sinus. The patient was operated on approximately one week after the presentation without any complications. DSA performed one day after the operation showed no signs of residual AVM. The patient recovered fully and, two months later, returned to finish his military service.2.In the second patient, a mild developmental delay accompanied by minor dysphasia and fine motor skills was observed at the beginning of childhood. Later in childhood, sensorineural hearing difficulty was diagnosed, and the patient received hearing aids for both ears. At the age of eight, he was operated on for a microform cleft lip.Almost 26 years later, the late follow-up DSA showed a recurrent AVM in the same location. The maximum diameter was 2.3 cm. It received arterial feeding from the left MCA, PCA, and external carotid artery (ECA) and drained to the vein of Galen and transverse sinus. MRI and 3D time-of-flight (TOF) MRA demonstrated the AVM, as well. The patient had been smoking from the age of 16 but stopped after the diagnosis of recurrent AVM. The patient had been completely asymptomatic for almost 26 years. At the time of the follow-up DSA, the patient was re-training for a new job and did not want to receive any additional treatment before finishing his studies. A follow-up has been scheduled.The patient suffered his first generalized tonic-clonic seizure at the age of 11. Brain MRI and MRA were performed, which showed a right-sided parietal AVM in the Sylvian fissure. The patient was referred to the neurosurgical department at the age of 14. On admission, he did not show any signs of neurological problems. The DSA showed an AVM of approximately 2 cm in diameter that received arterial feeding from the MCA branches and drained via two large veins to the superior sagittal sinus (SSS). AVM was embolized during the same anesthesia, and it was planned to be operated on immediately. After the embolization, however, AVM filling and shunting were no longer observed, but one of the draining veins partly filled at the same time as the other veins. The operation was canceled, and control DSA was scheduled for 6–12 months later. Post-embolization brain CT showed no signs of bleeding, although minor bleeding cannot be ruled out because of the radio-opacity artifact from embolization. Six months later, before the follow-up DSA, the patient suffered a new generalized seizure. The brain MRA and the following DSA showed a recanalized AVM. No bleeding was observed. AVM was operated on a few months later, and during the operation, signs of old bleeding were observed. The operation was uneventful and postoperative DSA, done immediately, showed complete eradication of AVM. The one-year follow-up DSA performed showed no signs of AVM residual or recurrence. Fourteen years later, the late follow-up DSA showed recurrent AVM in the same location. An elective operation was scheduled. The patient had been smoking since the age of 14. He had been seizure free for many years and did not have any symptoms of the recurrent AVM  and obstructive hydrocephalus. An external ventricular drain (EVD) was inserted. The DSA revealed a small AVM, 1 cm in diameter, that received arterial feeding from the posterior inferior cerebellar artery (PICA) and drained via one vein to the confluence of sinuses. The patient was operated on successfully, and immediate postoperative DSA showed no signs of residual AVM. The patient was left with minor ataxia, muscular hypotonia, lower limb weakness, and cognitive impairment. Now as an adult, the patient lives independently, walks without assistance, goes to the gym, and has completed a bachelor’s degree. At the age of 17, he was diagnosed with pulmonary AVM, which was incidentally found during a heart MRI. The genetic assessment revealed an ENG mutation, and the HHT diagnosis was confirmed. After the HHT diagnosis, brain MRI and TOF-MRA, performed in March 2020, showed no signs of recurrent AVMs. One year and three months later, the late follow-up DSA showed recurrent HHT-related AVM in the same location as the original AVM. The patient received stereotactic radiotherapy; follow-up continues.Two recurrent sporadic AVMs and one recurrent HHT-AVM were detected in the long-term follow-up DSA of patients who were treated under the age of 21 for an unruptured or ruptured AVM. The recurrence rate in our study was 4.9% for sporadic AVMs and 7.1% if HHT-AVM was included; this is in line with the 4.8% reported in the latest meta-analysis of 1134 AVMs .Recurrent sporadic AVMs were detected 26 years and 14 years after the previous angiographies. The patient who developed recurrence 14 years later had also had AVM recanalization six months after the primary treatment of endovascular embolization. After the recanalization, he was surgically treated, and the one-year control DSA showed no signs of AVM.AVM rupture has been associated with later recurrence , 33, as The two patients who developed recurrent sporadic AVM had been smoking practically their whole lives (from their teenage years). While impossible to draw any conclusions only from these cases, it is still worth mentioning. We recently reported smoking to be more frequent in brain AVM patients than in the general population 48 vs. 19%) . Nicotin vs. 19% Despite the accumulating evidence of AVM recurrences in the pediatric population, there is no consensus on the optimal follow-up strategy for these patients. Lang et al. reported four recurrent AVMs at 50 weeks, 51 weeks, 56 weeks, and 60 weeks from initial resection, of whom two had had earlier negative angiograms three and six months postoperatively, but no later recurrences were detected at the five-year angiography . HoweverOne of the patients in the cohort study of Lang et al. had MRA performed 10 months after the AVM surgery because of a seizure, which showed no signs of AVM, but two months later, one year after the surgery, the DSA showed a Spetzler-Martin grade II AVM . A similA recent meta-analysis suggested different AVM recurrence rates based on treatment modality, with the lowest rate of 0.7% in the radiosurgery group compared to 8.5% in microsurgery and up to 36.4% in endovascular embolization . It was The perinidal capillaries of AVM have been reported to be abnormal, with the absence of blood-brain barrier components and markedly dilated lumens , 31, 36.Fish et al. demonstrated that KRAS gain-of-function mutations on endothelial cells result in the creation of brain AVMs in mouse and zebrafish models and that these lesions may be reversed by inhibiting MEK signaling . In a 14Endovascularly treated patients should be followed with DSA at 6 months and 2 years and thereafter every 5 years until the last control is performed at the age of 21 or older.Microsurgically treated patients should be followed with DSA every 5 years until the last control is performed at the age of 21 or older.After radiosurgery, MRI+MRA are performed annually until the complete occlusion is suspected and then verified with DSA. Once complete occlusion is verified with DSA, patients should be followed with DSA every 5 years until the last control is performed at the age of 21 or older.If AVM obliteration has been achieved less than 5 years before the age of 21, at least one 5-year control DSA and one 10-year control MRA are performed.Our study does not provide enough evidence to suggest any specific follow-up protocols for patients with HHT-related AVMs. The risk of recurrence seems high, and the follow-up protocol should be tailored, preferably in multi-professional teams.Based on our study and the current literature on recurrent AVMs, we have adopted the following pragmatic, general follow-up strategy in our center for AVM patients treated in childhood or early adulthood (<21 years).As the patients, circumstances, and lesions vary highly, individual planning on follow-up should always be considered first.Two recurrent sporadic AVMs and one recurrent HHT-AVM were detected in the long-term surveillance DSA of patients who were treated under the age of 21. The recurrence rate in our study was 4.9% for sporadic AVMs and 7.1% if HHT-AVM was included. All the recurrent AVMs had bled and were originally microsurgically treated. The two patients with sporadic AVM recurrence had been smoking their whole lives. While it is still largely unknown why young AVM patients are more susceptible than older patients to an increased risk of developing AVM recurrence, the phenomenon is real, and therefore, imaging follow-up is recommended.


Video games, specifically action video games, have been demonstrated to be a useful tool in improving certain visual aspects in the general population. Visual attention span, the ability to simultaneously process multiple distinct visual elements during a single fixation, has been shown to improve among action video game players. The goal of this study was to verify that visual attention span is better not only in action video games, but also in other video game genres such as sports simulators or role-playing games. A total of 41 participants, aged 18 to 40 years old, were asked about the type of video games they were playing, name and genre, and the frequency of play. Visual attention span was assessed in all participants. Participants were divided into 4 groups according to the genre of video game they played. The total percentage of letter identification in the visual attention span was not significantly different between groups. A significant difference was found in the sixth position letter, and the right hemifield performance between groups, especially in sports simulators and action video game participants who showed a better performance. The action video game group showed a significant correlation between visual attention span performance and weekly hours played. Playing regularly different genres other than action video games can contribute to raise visual attention resources. Time play varies across countries but it confirms a global trend of video games becoming a new and popular form of entertainment. In 2023, there were approximately 3.07 billion active video gamers worldwide2. In parallel, electronic sports (eSports), competitions of video games regardless of the genre, are becoming increasingly popular with an audience of about 261.2 million people in 20223.Widespread use of video games is very common in our world and includes a variety of platforms , which are used mainly for leisure and social time. According to Statista, video game players spend an average of 8.5 h a week playing video games6. These fast-paced commercial video games, for instance, Call of Duty®, Medal of Honor®, or Counter Strike®, create an environment to foster these visual skills, in contrast to other video game genres, more slow-paced, such as Tetris® or The Sims®7.Video games include a wide range of genres such as action, sports, multi-online battle arena (MOBA), role-playing games (RPG), music and social simulators. In particular, action video games (AVG) are the most studied genre in the research literature and have become an interesting tool due to their potential to improve certain visual functions5, multi-object tracking4, attentional blink5, and in facilitating the learning process and modulating the resources to allocate attention more effectively during specific tasks9, for more information, see the reviews of Bavelier et al.10 and Bavelier and Green11. Because of these mechanisms, previous research has used AVG to improve vision abilities in a broad range of clinical applications such as visual acuity in amblyopia13, reading performance in dyslexia16, or improving visual and attention skills in brain damage18.Some studies have shown an improvement in visual spatial attention due to AVG training such as useful field of view21. In particular, AVG players have been shown to have a better performance in a visual attention task known as visual attention span (VA span)22. Antzaka et al.22 compared the performance between action and non-action video game players and concluded that VA span is better in action video game players, in line with previous studies about the possible effect of these fast-paced video games on the visual attention domain24.VA span refers to the capacity to process distinct visual elements simultaneously in one fixation and has been linked to reading performance22, that is to evaluate va SPAN in AVG players and in non-video game players. In the present study, va SPAN has also been measured and compared in video game players of other genres such as MOBA/RPG and sports simulators. The author's hypothesis is that improvements in VA span are not limited to players of AVG but are extensive to players of other video game genres.However, other genres of video games than AVG, such as multi-battle online arenas (MOBA), role-playing games (RPG), and sports simulators , can include high visual attention demands that could also lead to higher visual processing. Despite that, to our knowledge, there is no research exploring the possible benefits of video game genres other than AVG in improving VA span. The purpose of our study was to replicate the experimental methodology of Antzaka et al.Participants aged between 18 and 40 years, all university students, were recruited from January to June 2023 from two different colleges in the Polytechnic University of Catalonia . All participants provided informed consent prior to enrolling in the study. The study protocol was approved by an institutional review board  and conducted according to the tenets of the Declaration of Helsinki.Participants were asked to fill out a questionnaire about the video games played and the amount of time spent with each one. The questionnaire consisted of a list of commercial video games and a checklist with three different weekly hours ranges: 0–1, 3–5, and 5–10 h/week. The participants were instructed to list the video games they had played in the past six months and to indicate the amount of time they had spent playing each game.The video games selected were classified into three different genres: (a) action video games (AVG), (b) sports simulators (SIM), and (c) comprising both MOBA and RPG (MOBA/RPG). We provided commercial names in every genre to help participants select the time range. In order to be included in the study, participants had to play a minimum of 5 h/week in one category genre and no more than 1 h/week in the other genres. In addition, participants were asked to report as accurately as possible the number of hours per week spent playing video games, regardless of the genre, during the 6 months before the start of the study. Participants playing less than 1 h/week were included as non-video game players (NVG). Then, participants that meet the inclusion criteria were divided into 4 groups: (1) players of AVG, (2) players of sports simulators (SIM), (3) players of MOBA/RPG, and (4) non-video game players (NVG).22 using solely the global report, as the previously cited study did not find any advantage in the AVG group across the letter positions .All participants had a best-corrected visual acuity of 20/20 in each eye at distance and near and a stereoacuity of 50" or better, evaluated with Randot Stereo Test . VA span was measured using the same methodology as Antzaka et al.The global report consisted of a sequence of six letters made out of 10 possible consonants , presented randomly in each trial and without letter repetition within the sequence. The whole string subtended a visual angle of 6º, using a laptop computer  at 60 cm of distance. Trials began with the presentation of a central fixation point for 1000 ms, followed by a blank screen for 50 ms, and displaying the string of letters for 200 ms  was used to study the possible difference between groups and genres. A p-value < 0.05 was used as a threshold of statistical significance. SPSS version 28 for Windows was used for the analysis. Sample size calculation was calculated using G*Power software25, and data from Antzaka et al.22. This free-availabe software includes a power analysis and is able to calculate a required sample size using input parameters  and different power analyses depending on the statistical test . Moreover, G*Power can calculate post-hoc power analysis based on the results. For our study, we included the input using the same design and results from Antzaka et al., 2017, with a total of 42 participants, 13 per group, assuming an alpha risk of 0.05, 0.20 beta risk, a standard deviation of 5, and 7 for the minimum expected difference.VA span performance was computed as a percentage of accurately reported consonants for the total trials. A string of six letters was presented, each letter of the string was calculated as a percentage . Global VA span was calculated as the median of all the percentages obtained from all the six-letter string presentations. Kolmogorov–Smirnov test was applied to check the normality of the data. Non parametric one-way ANOVA  was applied to study the differences of VA span between groups. The proportion of corrected letters identified in each hemifield was calculated to study the possible effect on their performance. The sum of percentages  from letter positions 1 to 3 was considered as the global percentage for the left hemifield, and the sum of percentages from letter positions 3 to 6 as the right hemifield. Correlation analysis was calculated using Pearson (r) or Spearman (rho) test, depending on the parametric or non-parametric distribution from the Kolmogorov–Smirnov test. Mean comparison between groups was calculated using Mann–Whitney test (U test), in the case of non-normal distribution. Hemifield differences were compared between the sum of the correct percentage on the left, letters from 1 to 3, and on the right, letters from 4 to 6. Reading tasks were computed also as a correct percentage  for each task (PW1 and PW2). Chi-Square test .Informed consent was obtained from all individual participants included in the study.2 = 3.18, p = 0.365). Performance in both reading tasks measured as the percentage of correct words was not statistically significant between groups, PW1 (p = 0.319), and PW2, (p = 0.395).A total of 41 participants were included in the study, 27 males and 17 females, ranging from 17 to 36 years, mean and standard deviation 21 (2.92) years old. Participants were distributed into the four groups according to their answers in the questionnaire: 13  were identified and included in the action video game group (AVG), 6  in the sports simulators (SIM) group, 13  in the multi-online battle arena and role-playing group (MOBA/RPG), and 9  in the non-video game players (NVG). Chi-Square test did not find any statistical differences between groups and genres (χp = 0.097). Mean and standard deviation in the AVG was 85.96 (9.10), SIM, 87.08 (7.61), MOBA/RPG, 79.55 (12.95), and NVG, 74.90 (9.86).Global percentage in the VA span, as the sum of all letter correct percentages, was not statistically significant between groups (p < 0.0001), and PW2 (rho(41) = 0.52, p = 0.0004)  = 0.63, p = 0.193), second letter (p = 0.489), third letter (p = 0.697), fourth letter (p = 0.085), and fifth letter (p = 0.258).The VA span performance, depending on the position in the string (from 1 to 6), was compared between groups. No statistical differences were found in the first letter   Table . Bonferrp = 0.011). Additionally, significant differences were observed in the identification of the fourth and sixth letters in the string  and , respectively. Figure Comparison between AVG and NVG revealed a statistically significant difference in overall VA span performance . However, individual group analysis showed that only the AVG group (n = 13) showed a statistical correlation, p = 0.039, in contrast with SIM and MOBA/RPG, p = 0.419, p = 0.966, respectively.The correlation between hours played weekly and the percentage in VA span was computed in all groups. The correlation between all video game participants (n = 32) was not statistically significant (rho(32) = 0.22, p = 0.435). However, right hemifield performance was statistically significant (p < 0.001) , and between the AVG group, (p < 0.001), SIM (p = 0.005), MOBA/RPG, (p < 0.001), and NVG (p < 0.001).Hemifield analysis from VA span performance showed no statistically significant differences in the left hemifield between groups, Kruskal–Wallis test p = 0.35. HowevOur initial hypothesis was to investigate if other genres of video games, such as sports simulators or MOBA/RPG, can also be used for training studies to enhance visual spatial attention. To test this, we conducted a cross-sectional study comparing the performance in the global VA span in participants with high experience in each genre of videogame. For this study, a total of 41 participants, 27 males and 17 females, ranging from 17 to 36 years, were included and divided into four groups of study. VA span and two pseudo-reading tasks were conducted and compared between groups.th letter but not in the full sequence explains the better performance in the right hemifield, showing a left bias in video game participants compared with non-video games, especially in action video games and sports simulators. In addition, video game participants in all genres  showed better performance in the VA span compared with non-video game players. Besides, if we compare only AVG and NVG we found a statistically significant difference in the global VA span performance, but not if we take into account the other video game genres. Antzaka et al.22 found better performance in the letter positions 4, 5 and 6 comparing action video game players and non-video game players, in contrast with our study which we found only in the 6th letter position with all the groups.In the present study, global VA span performance was not different between groups. However, the performance in identifying the letter shown at the right end (i.e. sixth and last letter), was significantly different, with better results in the action video game (AVG) and sports simulator (SIM) groups compared with the non-video game (NVG) group. This difference in the 626, including visual areas as in the occipital lobe27, and better functional connectivity between attentional and sensorimotor networks28. In addition, lower VA span performance, such as in developmental dyslexia, has been linked to reduced activation in the left superior parietal lobule29. Then, the asymmetries found in the global VA span between videogame genres, particularly SIM and AVG, seem to be related to different brain activation in visual attention tasks, especially during rapid visual simultaneous processing30. The better allocation of attentional resources in the right hemifield in videogame genres compared with non-videogame experience can also be indicative of better visuospatial resources in the periphery4. Hence, it seems that playing sports simulation video games can foster visual attention abilities with the same mechanisms that have been explored in AVG.In the hemifield analysis, we found better performance in the AVG, and also in the SIM group, compared with non-video game players. In our study, sports video game players performed better on the global VA span task, although not significant when compared to other groups, and showed better allocation of visual attention in the right hemifield than the AVG group. To our knowledge, there is no research explaining these results in players of sports simulation video games. However, existing published literature on AVG players shows different brain activation during verbal tasksThese results confirm our hypothesis that other genres such as sports simulators  can improve visual attentional abilities as well as AVG (i.e. first-person shooters). For instance, sports video games, such as soccer or tennis, create scenes where gamers need to be aware of the whole screen (i.e. periphery vision), and simultaneously pay attention to details in the centre , so that visual attentional resources are both distributed at the centre and the periphery as it happens with AVG video games. In MOBA/RPG video games, gamers need to be aware of the central screen with multiple items at the same time and also be aware of the minimap or other items outside the central field. Besides that, sports simulation video games seem to engage the visual attention resources better than MOBA/RPG, based on the global VA span and hemifield analysis.21, which involves better activation of brain cortical networks such as the dorsal and ventral pathways30. Better performance in this task requires better attentional resources to process multi-parallel items, which can be explained by the fact that fast-paced video games, not only AVG, display specific characteristics that force video game players to foster their visual attention resources. We found similar results as Antzaka and colleagues (2017) regarding reading performance and VA span. A strong correlation was found in both pseudotasks and global VA span performance between all participants. Even though no statistical differences were found between groups in pseudo-reading tasks, we confirm the causal relationship between VA span and reading performance in our study. Hence, participants who had better global VA span read the pseudowords tasks more accurately, in accordance with previous literature21. VA span performance can be affected by multiple factors, such as reading experience20, or language31. In this study, all participants spoke the same languages , read both from left to right, and had no differences between reading pseudowords.Better performance in the global VA span has been linked to better reading abilities and attention resources32. However, the number of hours played in video games of other genres such as sports simulators and MOBA/RPG were not statistically correlated with VA span performance. Some authors suggest that the possible transference in improvements in visual and auditory domains caused by playing action video games is time-dependent33. A possible explanation for these differences in correlation between time playing and VA span performance could be the differences in mechanisms that facilitate brain plasticity and transference in each domain for each video game genre.In the AVG group, a statistically significant correlation was found between hours played weekly and VA span performance. These results can be attributed to the fact that playing these video games engages learning resources and promotes brain plasticity through the visual systemFuture training studies including action video games and sports simulators will confirm the causal relationship between VA span and playing specific video game genres. Our study has some limitations which make it difficult yet to establish this causal relationship. First, it comes from the participants sample, a post hoc analysis for the whole sample (N = 41) was calculated using G*Power software, for the 6-letter position using the one-way ANOVA fixed effect and alpha error 0.05. The power achieved was 0.97 (97%) for this study for global VA span analysis. However, the hemifield results gave a posthoc power of 0.66 (66%). Recruiting participants was especially difficult given the strict weekly hours for each group (> 5 h/week and < 1 h/week in the other genre) and took us 6 months of recruiting to complete our final sample of 41 participants.36, others in the last year37, and some in the past two years38, to consider the inclusion criteria for AVG and NAVG players. The threshold number of hours per week to classify participants between AVG and NAVG is also variable and ranges from a minimum of three hours per week to more than twenty hours per week38.There is also a freely available questionnaire developed from Bavelier Lab that can be used for recruiting participants into AVG and NAVG players, based on their videogame experience39. In our study, we use the same criteria for every group of video game experience. Future interventional studies training with different videogame genres will clarify the results obtained in our study. However, we consider that our results using a strong criteria of inclusion between groups postulate that not only AVG can foster visual attention abilities as previous research had shown, but sports videogames such as football or tennis or MOBA/RPG can also be considered.Moreover, there is high variability in research using questionnaires to include participants in video game experience in cross-sectional studies. Some published literature consider the number of hours played in the last six months41. In the present study, of the 41 participants, 17 were females, and Chi-Square test did not find any significant difference between groups. For instance, in Antzaka et al.22 action video games group of 19 participants, 14 were males. In the AVG group of the present study, five of the 13 participants were women, in the sports simulation group 2 out of 6 were women, 4 females in the MOBA/RPG and 6 in the NVG. Other cross-sectional research studies involving recruiting participants in action and non-action video game groups have been published with gender bias, which could be explained by the fact that males generally play more video games than females42.Gender bias in our study was an additional factor, even though other studies have been published with such biasVisual attention distribution and allocation of resources during the VA span task are better in sports simulation and in action video game players, especially in the right hemifield, than in MOBA/RPG and non-video game players. Future work can also contemplate other genres of video games to study the possible applications to improve visual functions.


Adolescent and young adult solitary drinking is prospectively associated with alcohol problems, and it is thus important to understand why individuals engage in this risky drinking behavior. There is substantial evidence that individuals drink alone to cope with negative affect, but all prior studies have assessed motives for alcohol use without specifying the context of such use. Here, we directly compared solitary-specific drinking to cope motives with general drinking to cope motives in their ability to predict solitary drinking behavior and alcohol problems. We hypothesized that solitary-specific drinking motives would provide additional predictive utility in each case.N = 307; 90% female; ages 18–20) recruited from a TurkPrime panel March-May 2016 completed online surveys querying solitary alcohol use, general and solitary-specific coping motives, and alcohol problems.Current underage drinkers . Additionally, both general and solitary-specific coping motives were positively associated with alcohol problems, again controlling for enhancement motives, but the model including general motives accounted for greater variance (0.49) than the solitary-specific motives model (0.40).Both solitary-specific and general coping motives were positively associated with a greater percentage of total drinking time spent alone in separate models, after controlling for solitary-specific and general enhancement motives, respectively. However, the model with solitary-specific motives accounted for greater variance than the general motives model based on adjusted RThese findings provide evidence that solitary-specific coping motives explain unique variance in solitary drinking behavior but not alcohol problems. The methodological and clinical implications of these findings are discussed. Similarly, using large national samples of US adolescents followed for 17 years, Creswell and colleagues )lleagues  recentlyIn addition to problematic alcohol consumption, solitary drinking is associated with several other negative psychosocial factors in adolescents and young adults, including problems in emotional, social, academic, and legal domains e.g., –15). For. For15])r = 0.28 https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  31 Jan 2023Reviewer #1: 1) Given the nuanced nature of the hypothesis and objectives, it was interesting to see that authors tried to separate the motives – solitary-specific vs. general – in predicting the proportion of time spent in solitary drinking. The range of solitary drinking time reported by the individuals seems broad but on the low end. I was wondering about how the results might be different (strengthened?) if the authors had screened for a sample with greater prevalence of solitary drinking. Perhaps the authors can mention this potential limitation and consider this as a future direction.This is a good point, and we have now included it in the discussion section on pages 15 and 16: “A final point of consideration is that this sample reported drinking alone for approximately one third of their total drinking time; while it is common for young adults to spend more time drinking socially than solitarily , findings may have been strengthened if the sample was screened for those who engaged more often in solitary drinking. This is especially important as the variance across models 1 and 2 was small (0.03 and 0.08) indicating that, at least among this sample, the included variables only explained a small proportion of solitary drinking. Future studies that focus on individuals who primarily drink by themselves may shed further light on solitary drinking motives and their relation to solitary alcohol consumption and alcohol problems.”2) Another way to examine the relationships being pursued in this manuscript would be to contrast the motives for drinking alone vs. drinking with others. This was particularly suggested by the finding that solitary-specific enhancement motives were a significant predictor of solitary drinking. Perhaps the authors considered modeling the proportion of time spent drinking with others as a function of the drinking motives – general vs. solitary-specific – to get additional insights on the predictors of the two different drinking patterns. Given that the sample had a mixed drinking pattern , there might be some interesting insights to be gleaned by comparing the results of complementary analyses of solitary drinking time and of drinking time with others. Perhaps this is beyond the scope of this manuscript and/or a future direction of the authors.We agree with the Reviewer and in fact our measure of solitary drinking was a continuous scale that assessed the proportion of time spent drinking alone versus with others. As such, this one item includes information on both solitary and social drinking . Thus, the analyses already are a function of both solitary and social drinking and cannot be run separately. Thank you for the opportunity to review this interesting work!We appreciate this nice comment!Reviewer #2: Intro1. Augment the recent theoretical model  with the seminal motivational model of alcohol  for greater grounding.We now briefly describe the Cox and Klinger motivational model to provide grounding for the theoretical account made by Creswell and others on page 4: “According to Cox and Klinger’s motivational model for alcohol use [20], individuals choose to drink based on expected affective changes that drinking will produce including increasing positive emotion and/or decreasing negative emotion. In line with the latter, several researchers , and a recent theoretical model [1], have hypothesized that solitary drinking is motivated by the desire to alleviate negative affect.”Methods2. Insert the time period of data collection.We now note on page 6 the time period over which data was collected: “Participants were drawn from a parent study of current underage  drinkers residing in the United States, who were recruited through an Amazon TurkPrime panel from March 2016 to May 2016 .”3. I am unsure of the value of further describing participants as "84.36% identified as non-Hispanic/Latino". Perhaps there is a social significance unknown to me and others who would benefit for some commentary related to this description.We report percentage of non-Hispanic/Latino individuals as this is a separate construct from race and further contextualizes the sample. Additionally, including information on Hispanic/Latino percentages is standard in the literature . Results4. At line 209, what is labelled as Model 2 should be Model 4.We appreciate the Reviewer’s attention to detail. We have corrected this label to read Model 4.Discussion5. While Models 1 & 2 are significant, the variance (8% and 3%) accounted by the models requires tentative discussion to avoid overplaying the effect of the included variables.We now provide a brief discussion of the variance of models 1 and 2 on pages 15-16, noting that the included variables only explained a small proportion of solitary drinking .Abstract6. Include gender distribution of participants and time/dates of data collection to aid readers appraise the study from the get go.We have added gender distribution and time of data collection to the abstract, as suggested.8. Include the magnitude of the variance explained by models.We have added this to the abstract, as well. 17 Feb 2023Solitary-specific drinking to cope motives explain unique variance in solitary drinking behavior but not alcohol problems compared to general drinking to cope motivesPONE-D-22-20380R1 <span style="color: rgb; font-family: verdana, geneva, arial, helvetica, sans-serif; font-size: 11.2px; background-color: rgb;"> SKRZYNSKI </span> Dear Dr. We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact Kind regards,Anthony A. Olashore, PhD, FWACPAcademic EditorPLOS ONE 23 Feb 2023PONE-D-22-20380R1 Solitary-specific drinking to cope motives explain unique variance in solitary drinking behavior but not alcohol problems compared to general drinking to cope motives Dear Dr. Skrzynski:I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. 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Brazilian National Survey on Child Nutrition (ENANI-2019) results, this article reflects on the adequacy of the “malnutrition in all its forms” framework and system of classification for representing and interpreting these dietary transitions in Brazilian children. We highlight the limitations of this classification system, including the focus on health outcomes and anthropometric measures, the siloed understanding of these forms of malnutrition, the lack of relevance of the obesity category to children under 5 years old, and the failure to adequately address the various measures of poor quality diets captured by ENANI-2019. As an alternative, based on an approach developed by Gyorgy Scrinis to reframing malnutrition in all its forms, we suggest a need for frameworks that focus on describing and classifying the nature of, and changes to, dietary patterns, rather than focused on health outcomes.Based on the  There are other previous frameworks that provide ways of describing and analyzing the types of dietary transformations experienced worldwide, particularly frameworks that provide ways of measuring and evaluating the quality of food-based rather than nutrient-based dietary patterns There also are not any similar frameworks for classifying and representing transformations in the “health impacts” associated with these dietary transformations. Nutrition transition partially intends to capture the shift in forms of malnutrition, from undernutrition to the so-called “overnutrition”, obesity, and noncommunicable diseases (NCDs). The notion of “malnutrition in all its forms” has become the dominant way in which these myriad forms of malnutrition and dietary health issues are now being defined and measured Brazilian National Survey on Child Nutrition (ENANI-2019) show a mixed scenario of dietary and health transformations, with some encouraging indicators suggesting improvements in dietary health in Brazil, and others signaling the persistence of old problems and a continued rise in relatively new ones. The health indicators suggest an improvement in some conditions traditionally related to undernutrition issues (anemia and vitamin A deficiency), alongside the continued rise in excess weight The results of the Based on the approach developed by Gyorgy Scrinis ,,,Brazilian National Survey of Demography and Health (PNDS 2006) The findings of ENANI-2019 have been extensively described in other articles in this special issue Overall, considering the geographic regions of the country, the maternal education levels and maternal race/skin color, the socio-demographic disparities in the prevalence of anemia, vitamin A deficiency, stunting, and breastfeeding decreased from 2006 to 2019. On the other hand, disparities between geographic regions increased for excess weight in this same period ,Considering the food that children 6-59 months of age had consumed on the day before the ENANI-2019 interview, 55.6% reached the minimum dietary diversity recommended by the WHO The dominant approaches to represent, measure, and analyze malnutrition are the dualistic and the tripartite classifications, which define and divide malnutrition into either two categories - undernutrition versus overnutrition/obesity; or three categories - chronic undernutrition, micronutrient deficiencies, and obesity/overweight. For example, WHO distinguishes between the three categories of undernutrition, micronutrient-related malnutrition, and overweight/obesity/diet-related noncommunicable diseases This classification emerged in the late 1990s from the attempt to expand the earlier focus on malnutrition as undernutrition/hunger ,These categories of malnutrition are intended to represent and classify the “nutritional status” of a person. Malnutritional status is generally understood as a state of nutrition related to an inadequate diet, and that may then lead to other diseases or negative health outcomes The way in which these forms of malnutrition have been defined suggests that there are fairly clear and direct relationships among the three temporal stages of (i) dietary intake; (ii) nutritional status; and (iii) health outcomes. This has led to a siloed understanding of these three forms of malnutrition as being separate and distinct.Undernutrition is defined as a state of nutrient deficiency. This is generally defined in terms of an insufficient energy intake, measured in calories/kilojoules. Undernutrition also includes a state of micronutrient deficiency, although the category of micronutrient deficiencies specifically addresses this condition. Being in a state of undernutrition can lead to health outcomes such as stunting and underweight, which are defined by anthropometric measures. There is no way to directly measure the nutritional state of inadequate energy intake. Instead, the prevalence of stunting and underweight outcomes are used to measure and represent its prevalence. However, stunting in childhood has also been linked to the incidence of obesity in adulthood Micronutrient malnutrition typically refers to the nutritional status of being deficient in one or more micronutrients. As a standalone category of malnutrition, it can also refer to a state of sufficient energy intake, while lacking the intake of specific micronutrients. Micronutrient malnutrition relates to the common contemporary condition of consuming an adequate quantity of food but insufficient dietary quality and diversity. Micronutrient malnutrition is defined in very nutrient-specific terms. The dietary determinants of micronutrient malnutrition are defined as a dietary pattern deficient in specific micronutrients, which leads to a poor nutritional status in these specific micronutrients and, in turn, to micronutrient deficiency-related diseases, such as iron-related anemia. There are also non-dietary determinants of micronutrient deficiencies, such as unhealthy environments and inadequate child care practices The category of obesity/overweight is also sometimes referred to as “overnutrition”, although the later term is now rarely used, probably because of its problematic assertion that one can be “over-nourished”. Nevertheless, a primary dietary determinant of obesity is generally assumed to be excess of energy or nutrients-to-limit intake , which are in turn associated with unbalanced, poor-quality and high in ultra-processed foods diets ,The siloed understanding of these three forms of malnutrition implies that separate groups of people are experiencing these forms of malnutrition. Yet, there is abundant evidence to suggest that each of these forms of malnutrition is associated with multiple dietary determinants and health outcomes. The studies on the double-burden of malnutrition, for example, have stressed the interconnections between these multiple forms of malnutrition, such as those between stunting, micronutrient deficiencies, and obesity Another limitation of the conventional classification and definitions of malnutrition is that they are defined in nutrient-specific terms: inadequate or excess energy intake, insufficient micronutrient intake, and excess nutrients-to-limit are the dietary exposures of concern. But these nutrient-specific definitions do not adequately address the quantity, diversity, and quality of dietary patterns that contribute to poor health and cannot be reduced to specific nutrients or nutrient profiles.A more general limitation of this conventional classification and definition of malnutrition is that it does not directly address the incidence of inadequate and poor quality diets. Diets that may be sufficient regarding energy intake but are based on nutritionally unbalanced ultra-processed foods combined with a lack of diversity of minimally-processed foods are not well represented in this framework, other than as a form of “overnutrition” and as possible contributors to obesity and NCDs. Poor-quality diets - particularly those consisting of ultra-processed foods - are primarily measured via their influence on obesity, rather than for other types of health impacts that may be independent of obesity and body fat. High ultra-processed food intake in low-income countries has also been associated with micronutrient deficiencies and low dietary diversity ,In the case of children under 5 years old, the category of obesity/overweight is even less relevant than for adults, as children are less likely to achieve overweight or obese BMI status before this age, although the incidence of overweight has been increasing in Brazil and other countries, even in this age group This also highlights some limits of measuring diet and health outcomes based on anthropometric measures. One of the consequences of measuring malnutritional status with anthropometry, or other diet/health outcomes, is the long lag in time between dietary intake and these health outcomes. The narrow framing of these forms of malnutrition regarding nutrient-specific determinants and health-specific outcomes, and as separate siloed conditions, also promotes the idea that each form of malnutrition can be addressed separately, through separate and nutrient-specific or technological “solutions”.The limitations of the tripartite classification of malnutrition in all its forms are evident if applied and used to interpret the ENANI-2019 survey data. Some of the ENANI-2019 survey parameters can be mapped onto the three forms of malnutrition, but others do not neatly or exclusively fit, or do not fit at all, into one of these categories. The category undernutrition consists of the anthropometric measures: low height-for-age (7%), low weight-for-age (2.9%), and thinness (3%). Although these values are low, the fact that older children present better results in the indicator height-for-age compared to younger children, and the finding of some increase in the prevalence of low weight-for-age and thinness indicators, suggests a deterioration of living conditions in recent years. Inadequate breastfeeding (54% of the children < 6 months were not exclusively breastfed) could also be understood as a type of undernutrition.,Micronutrient deficiencies - those that have been directly measured in the body - are vitamins A (6%), B12 (14.2%) and D (4.3%), Zinc (17.8%), and the prevalence of anemia (10.1%) ,The obesity category is measured by the prevalence of excess weight (10.1%), of which 3% are obese. The increase in excess weight from 6.6% to 10.1% suggests that this form of malnutrition - and its associated dietary determinants - are becoming a more serious problem. But given the age of the children, even this increase may be underestimating the scale of this problem. Ultra-processed foods consumption is the dietary indicator most strongly linked to obesity. The fact that 89% of children had consumed ultra-processed foods, with 43% having consumed three or more types of these foods, shows that this is already a major concern and a significant contributor to poor-quality diets. Studies surveying the consumption of ultra-processed foods in Brazilian adults have demonstrated substantial increases in consumption of ultra-processed foods over this period, and this is likely to be reflected in increases in children’s consumption There are various indicators of poor-quality diets that do not easily map into the obesity category. Aside from ultra-processed foods consumption, low minimum dietary diversity (55%) and non-consumption of fruit and vegetables (25%) are also concerning. The lack of data on how these parameters have changed from 2006 to 2019 also hinders the generalization about dietary trends over this period; however, these indicators suggest that a significant proportion of children may be accessing an energy-sufficient diet but increasingly relying on cheap ultra-processed foods and a narrow range of fresh and minimally processed foods. Such poor-quality dietary patterns may be contributing to more than one of the three conventional categories of malnutrition, such as micronutrient deficiencies and overweight While the ENANI-2019 provides evidence of a decline in some indicators of undernutrition/deficiency conditions, and a rise in obesity/“overnutrition” indicators, interpreting these results as a simple (and inevitable) shift from “under” to “over” nutrition may be both simplistic and misleading, and may mask some more divergent and contradictory trends in dietary patterns. The conventional categories of malnutrition are currently defined based on health outcomes and anthropometric measures. Therefore, the notion of “nutritional status” is not addressing directly whether people are consuming a nourishing diet, one that is adequate and proportionate in terms of diet quantity and quality. Malnutrition could instead be defined, classified, and measured by the type of dietary patterns. Unfortunately, there are no well-established systems for classifying different types of dietary patterns that could capture and categorize the dietary transformations or nutrition transitions taking place in Brazil and other countries.,Some of the parameters that could classify dietary patterns include those addressed in the ENANI-2019 survey: ultra-processed food consumption as well as other NOVA categories; dietary diversity; fruit & vegetable consumption; and breastfeeding. One clear trend worldwide is the emergence of dietary patterns dominated by ultra-processed foods, particularly in high-income countries such as the United States and the United Kingdom, which could be categorized as “ultra-processed dietary patterns” With the rising price of fresh foods and animal products in recent years and the successive reductions in the price of ultra-processed foods in Brazil Beyond the re-definition and re-classification of malnutrition status, there is equally a need to develop frameworks capable of defining and measuring the multiple and varied dietary transitions and transformations occurring worldwide, both between and within countries and populations