Building Capacity for Research on Community Doula Care: A Stakeholder-Engaged Process in California.

PURPOSE: In an effort to address persistent inequities in maternal and infant health, policymakers and advocates have pushed to expand access to doula care. Several states, including California, now cover doula services through Medicaid. As coverage expands, research on the impact of doula care will likely increase. To develop best practices for research, it is critical to engage community doulas, clients, and other key stakeholders. DESCRIPTION: Our overarching goal was to build capacity for future doula- and client-centered research on community doula care. First, we established a Steering Committee with members from seven relevant stakeholder groups: community doulas, former or potential doula clients, clinicians, payers, advocates, researchers, and public health professionals. Second, we conducted a needs assessment to identify and understand stakeholders' needs and values for research on community doula care. Findings from the needs assessment informed our third step, conducting a research prioritization to develop a shared research agenda related to community doula care with the Steering Committee. We adapted the Research Prioritization by Affected Communities protocol to guide this process, which resulted in a final list of 21 priority research questions. Lastly, we offered a training to increase capacity among community doulas to engage in research on community doula care. ASSESSMENT: Our findings provide direction for those interested in conducting research on doula care, as well as policymakers and funders. CONCLUSION: The findings of our stakeholder-engaged process provide a roadmap that will lead to equity-oriented research centering clients, doulas, and their communities.

Septins provide microenvironment sensing and cortical actomyosin partitioning in motile amoeboid T lymphocytes.

The all-terrain motility of lymphocytes in tissues and tissue-like gels is best described as amoeboid motility. For amoeboid motility, lymphocytes do not require specific biochemical or structural modifications to the surrounding extracellular matrix. Instead, they rely on changing shape and steric interactions with the microenvironment. However, the exact mechanism of amoeboid motility remains elusive. Here, we report that septins participate in amoeboid motility of T cells, enabling the formation of F-actin and α-actinin-rich cortical rings at the sites of cell cortex-indenting collisions with the extracellular matrix. Cortical rings compartmentalize cells into chains of spherical segments that are spatially conformed to the available lumens, forming transient "hourglass"-shaped steric locks onto the surrounding collagen fibers. The steric lock facilitates pressure-driven peristaltic propulsion of cytosolic content by individually contracting cell segments. Our results suggest that septins provide microenvironment-guided partitioning of actomyosin contractility and steric pivots required for amoeboid motility of T cells in tissue-like microenvironments.

Evaluation of the Impact of Meibomian Gland Dysfunction Using a Novel Patient-Reported Outcome Instrument.

Purpose: This study was intended to characterize the impact of meibomian gland dysfunction (MGD) on patients' quality of life. Methods: In this prospective, multicenter, noninterventional clinical study (NCT01979887), eligible individuals (age ≥40 years; absence of uncontrolled ocular/systemic disease) were categorized, based on composite grading of ocular symptoms, Schirmer score, and meibum quality, into (1) non-MGD, (2) mild/moderate MGD, or (3) severe MGD cohorts. The MGD Impact Questionnaire (MGD IQ), a 10-item patient-reported outcome measure, was self-administered at clinic visit on day 1, and readministered on day 22 to assess intervisit agreement regarding MGD IQ responses. Results: In total, 75 subjects were assigned to the study cohorts (25 per cohort). Across cohorts, MGD IQ item scores rose incrementally with increasing MGD severity. The severe MGD cohort experienced greater difficulty with reading and performance of leisure activities, greater time on eye care, and greater bother with eye care and eye appearance than the mild/moderate MGD cohort (all P < 0.05). Compared with the non-MGD cohort, the mild/moderate MGD cohort had greater difficulty working on computer, whereas the severe MGD cohort had greater difficulty reading, driving, and performing leisure activities, more frequent difficulty with outdoor activities, more time on eye care, and greater bother with eye care (all P < 0.05). Intervisit agreement between MGD IQ responses was fair to moderate (weighted kappa statistic 0.33‒0.58). Conclusions: Vision-related activities are negatively impacted by increasing severity of MGD. The MGD IQ instrument can help characterize disease severity and amplify the patient's voice in patient-centric clinical research. ClinicalTrials.gov NCT01979887.

Depletion of tet2 results in age-dependent changes in DNA methylation and gene expression in a zebrafish model of myelodysplastic syndrome.

Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and dysplasia. The gene encoding ten-eleven translocation 2 (tet2), a dioxygenase enzyme that catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine, is a recurrently mutated tumor suppressor gene in MDS and other myeloid malignancies. Previously, we reported a stable zebrafish line with a loss-of-function mutation in the tet2 gene. The tet2m/m-mutant zebrafish developed a pre-MDS state with kidney marrow dysplasia, but normal circulating blood counts by 11 months of age and accompanying anemia, signifying the onset of MDS, by 24 months of age. Methods: In the current study, we collected progenitor cells from the kidney marrows of the adult tet2m/m and tet2wt/wt fish at 4 and 15 months of age and conducted enhanced reduced representation of bisulfite sequencing (ERRBS) and bulk RNA-seq to measure changes in DNA methylation and gene expression of hematopoietic stem and progenitor cells (HSPCs). Results and discussion: A global increase in DNA methylation of gene promoter regions and CpG islands was observed in tet2m/m HSPCs at 4 months of age when compared with the wild type. Furthermore, hypermethylated genes were significantly enriched for targets of SUZ12 and the metal-response-element-binding transcription factor 2 (MTF2)-involved in the polycomb repressive complex 2 (PRC2). However, between 4 and 15 months of age, we observed a paradoxical global decrease in DNA methylation in tet2m/m HSPCs. Gene expression analyses identified upregulation of genes associated with mTORC1 signaling and interferon gamma and alpha responses in tet2m/m HSPCs at 4 months of age when compared with the wild type. Downregulated genes in HSPCs of tet2-mutant fish at 4 months of age were enriched for cell cycle regulation, heme metabolism, and interleukin 2 (IL2)/signal transducer and activator of transcription 5 (STAT5) signaling, possibly related to increased self-renewal and clonal advantage in HSPCs with tet2 loss of function. Finally, there was an overall inverse correlation between overall increased promoter methylation and gene expression.

Hierarchical assembly of tryptophan zipper peptides into stress-relaxing bioactive hydrogels.

Soft materials in nature are formed through reversible supramolecular assembly of biological polymers into dynamic hierarchical networks. Rational design has led to self-assembling peptides with structural similarities to natural materials. However, recreating the dynamic functional properties inherent to natural systems remains challenging. Here we report the discovery of a short peptide based on the tryptophan zipper (trpzip) motif, that shows multiscale hierarchical ordering that leads to emergent dynamic properties. Trpzip hydrogels are antimicrobial and self-healing, with tunable viscoelasticity and unique yield-stress properties that allow immediate harvest of embedded cells through a flick of the wrist. This characteristic makes Trpzip hydrogels amenable to syringe extrusion, which we demonstrate with examples of cell delivery and bioprinting. Trpzip hydrogels display innate bioactivity, allowing propagation of human intestinal organoids with apical-basal polarization. Considering these extensive attributes, we anticipate the Trpzip motif will prove a versatile building block for supramolecular assembly of soft materials for biotechnology and medicine.

Dynein-Powered Cell Locomotion Guides Metastasis of Breast Cancer.

The principal cause of death in cancer patients is metastasis, which remains an unresolved problem. Conventionally, metastatic dissemination is linked to actomyosin-driven cell locomotion. However, the locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, a complementary mechanism of metastatic locomotion powered by dynein-generated forces is identified. These forces arise within a non-stretchable microtubule network and drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. It is also shown that the dynein-powered locomotion becomes indispensable during invasive 3D migration within a tissue-like luminal network formed by spatially confining granular hydrogel scaffolds (GHS) made up of microscale hydrogel particles (microgels). These results indicate that the complementary motricity mediated by dynein is always necessary and, in certain instances, sufficient for disseminating metastatic breast cancer cells. These findings advance the fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis.

Exploring Signs and Symptoms Associated with Meibomian Gland Dysfunction for Use as Clinical Trial Endpoints.

Purpose: Dry eye disease is attributed to impaired tear production and/or evaporative dry eye. Evaporative dry eye is frequently associated with meibomian gland dysfunction (MGD). The objective of this study was to identify clinical study endpoints related to MGD. Methods: This 22-day, noninterventional, case-control clinical study involved three cohorts with increasing MGD severity: no MGD, mild/moderate MGD, and severe MGD. Symptoms were assessed with an ocular symptom questionnaire grading blurred vision, eye burning, eye dryness, eye pain, light sensitivity, eye itching, eye foreign body sensation, and overall ocular discomfort. Sign assessments included the maximum meibum quality score (MMQS), tear breakup time, Schirmer tear tests, biomicroscopy, and corneal staining. Signs and symptoms were compared between cohorts and study visits. Results: Seventy-five study participants were assigned to the cohorts (25 per cohort). MMQS scores increased with increasing MGD severity, reflecting the selection criteria for the cohorts. Between-visit scores showed a weighted kappa statistic of 0.72 indicating substantial agreement. Mean scores of all assessed symptoms increased with increasing MGD severity. Scores for symptoms showed moderate (κ = 0.41-0.60) to substantial (κ = 0.61-0.80) agreement between visits. Overall ocular discomfort demonstrated the strongest correlation with the MMQS. Conclusion: The MMQS was a reproducible sign of MGD showing good agreement with ocular symptoms. Overall ocular discomfort was well correlated with typical dry eye symptoms and could potentially be used as a single measure of MGD symptoms. The findings from this observational study may inform endpoints for future clinical trials. ClinicalTrials.gov NCT01979887.

Dynamic and functional linkage between von Willebrand factor and ADAMTS-13 with aging: an Atherosclerosis Risk in Community study.

BACKGROUND: von Willebrand factor (VWF) is a multimeric glycoprotein critically involved in hemostasis, thrombosis, and inflammation. VWF function is regulated by its antigen levels, multimeric structures, and the state of enzymatic cleavage. Population studies in the past have focused almost exclusively on VWF antigen levels in cross-sectional study designs. OBJECTIVE: To identify subjects in the Atherosclerosis Risk in Community study who had persistently low and high VWF antigen over 10 years and to quantify longitudinal changes in the biological activities and cleavage of VWF in these subjects. METHODS: We measured VWF antigen, propeptide, adhesive activities, and cleavage by ADAMTS-13 quantified using a mass spectrometry method that detected the cleaved VWF peptide EQAPNLVY, as well as coagulation factor VIII activity. RESULTS: We determined the mean subject-specific increase in VWF to be 22.0 International Units (IU)/dL over 10 years, with 95% between -0.3 and 59.7 IU/dL. This aging-related increase was also detected in VWF propeptide levels, ristocetin cofactor activity, and VWF binding to collagen. We identified 4.1% and 25.0% of subjects as having persistently low (<50 IU/dL) and high (>200 IU/dL) VWF antigen, respectively. Subjects with persistently low VWF had enhanced ristocetin cofactor activity, whereas those with persistently high VWF had elevated levels of ADAMTS-13, resulting in a comparable rate of VWF cleavage between the 2 groups. CONCLUSIONS: These results provide new information about the effects of aging on VWF antigens and adhesive activity and identify a functional coordination between VWF and the rate of its cleavage by ADAMTS-13.

A Light-Promoted Innate Trifluoromethylation of Pyridones and Related N-Heteroarenes.

We report a practical, light-mediated perfluoroalkylation using Langlois' reagent (sodium trifluoromethylsulfinate) that proceeds in the absence of any photocatalyst or additives. This method has allowed for the facile functionalization of pyridones and related N-heteroarenes such as azaindole. This protocol is operationally simple, uses readily available materials, and is tolerable for electron-neutral and -rich functional pyridones. Cyclic voltammetry was utilized as a mechanistic probe, and preliminary data suggest the reaction may involve an electrophilic radical mechanism.

Supporting Birthing People and Supporting Doulas: The Impact of the COVID-19 Pandemic on a Community-Based Doula Organization in San Francisco.

Background: Beginning in March 2020, health care systems in the United States restricted the number of support people who could be present during pregnancy-related care to reduce the spread of COVID-19. We aimed to describe how SisterWeb, a community-based doula organization that employs Black, Pacific Islander, and Latinx doulas in San Francisco, California, adapted to the COVID-19 pandemic. Methods: As part of process and outcome evaluations conducted through an academic-community partnership, we interviewed SisterWeb doulas, mentors, and leaders in 2020, 2021, and 2022 (n=26 interviews). We identified preliminary themes using the Rapid Assessment Process and then conducted thematic analysis of data related to COVID-19. Results: SisterWeb leadership remained committed to safeguarding doulas by shifting to virtual support until doulas were onboarded as benefitted employees. Doulas reported hospital policies impacted clients' pregnancy-related care. Initially, doulas adapted to virtual support by connecting with clients more frequently through phone and text. When permitted to meet in person, doulas adjusted to client preference. Finally, as the pandemic impacted doulas' well-being, they turned to mentors for emotional support. Discussion and Health Equity Implications: This analysis contributes to a growing body of literature describing doulas' experiences during the pandemic. By shifting to virtual support, SisterWeb leaders prioritized the health, safety, and financial stability of doulas, who were members of communities disproportionately impacted by COVID-19. Our findings suggest that public health guidance, organizational COVID-19 precautions, and hospital policies hindered SisterWeb's goal of ensuring clients receive equitable medical care. In addition, we found that emotional support for doulas is vital to their work.

Single Administration of Bimatoprost Implant: Effects on 24-Hour Intraocular Pressure and 1-Year Outcomes.

PURPOSE: To evaluate the effects of a single bimatoprost implant administration on 24-hour intraocular pressure (IOP) lowering at 8 weeks, and 1-year IOP-lowering efficacy and safety outcomes. DESIGN: Multicenter, open-label, 12-month, phase 3b study (NCT04285580). PARTICIPANTS: Adults with open-angle glaucoma or ocular hypertension. METHODS: Participants (n = 31) received 10-µg bimatoprost implant in the study eye on day 1; IOP (sitting and/or supine) was measured with pneumatonometry every 2 hours throughout a 24-hour period at baseline and week 8. IOP was measured by Goldmann applanation tonometry (GAT) at hour 0 (8 am ± 1 hour) at baseline, weeks 8 and 16, and months 6, 9, and 12. MAIN OUTCOME MEASURES: The primary endpoint was the week-8 hour-matched change from baseline in habitual position IOP over 24 hours assessed with pneumatonometry. Hour 0 IOP change from baseline measured with GAT in study eyes that received no additional (rescue) IOP-lowering treatment, treatment-emergent adverse events (TEAEs), and central corneal endothelial cell density (CECD) were evaluated through 12 months. RESULTS: The mean (standard deviation [SD]) baseline IOP at hour 0 was 24.2 (2.70) mmHg and 25.3 (7.15) mmHg by GAT and pneumatonometry, respectively. Pneumatonometer measurements of IOP taken over 24 hours at week 8 with the participant in habitual position (sitting from 8 am to 10 pm, supine from 12 am to 6 am) showed consistent IOP lowering through the day and night and reduced fluctuation in IOP. The range in IOP measurements over 24 hours was reduced from baseline by a mean (SD) of -1.6 (2.98) mmHg. All 31 bimatoprost implant-treated participants completed the 12-month study; 23 (74%) required no rescue IOP-lowering treatment. The mean (SD) IOP reduction from baseline at month 12 in nonrescued eyes was -4.3 (3.35) mmHg. The most common TEAE was conjunctival hyperemia (incidence 35.5%, 11/31). No implant-treated eye had a ≥ 15% loss in CECD from baseline. CONCLUSIONS: A single intracameral administration of the bimatoprost implant lowered IOP in the habitual position consistently throughout the day and night at week 8. The majority of participants continued to have reduced IOP for 1 year without additional therapy. The 1-year safety profile was favorable. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Riluzole in Spinal Cord Injury Study (RISCIS)-Pharmacokinetic (PK) Sub-Study: An Analysis of Pharmacokinetics, Pharmacodynamics, and Impact on Axonal Degradation of Riluzole in Patients With Traumatic Cervical Spinal Cord Injury Enrolled in the RISCIS Phase III Randomized Controlled Trial.

To date, no drug therapy has shown significant efficacy in improving functional outcomes in patients with acute spinal cord injury (SCI). Riluzole is an approved benzothiazole sodium channel blocker to attenuate neurodegeneration in amyotrophic lateral sclerosis (ALS) and is of interest for neuroprotection in SCI. In a Phase I clinical trial (ClinicalTrials.gov Identifier: NCT00876889), riluzole was well tolerated with a 2-week treatment at the dose level approved for ALS and exhibited potential efficacy in patients with SCI. The acute and progressive nature of traumatic SCI and the complexity of secondary injury processes alter the pharmacokinetics (PK) of therapeutics. In the PK sub-study of the multi-center, randomized, placebo-controlled, double-blinded Riluzole in Spinal Cord Injury Study (RISCIS) Phase II/III trial (ClinicalTrials.gov Identifier: NCT01597518), a total of 32 SCI patients were enrolled, and most of our patients were middle-age Caucasian males with head and neck injuries. We studied the PK and pharmacodynamics (PD) of riluzole on motor recovery, measured by International Standards for Neurological Classification of SCI (ISNCSCI) Motor Score at injury and at 3-month and 6-month follow-ups, along with levels of the axonal injury biomarker phosphorylated neurofilament heavy chain (pNF-H), during the 2-week treatment. PK modeling, PK/PD correlations were developed to identify the potential effective exposure of riluzole for intended PD outcomes. The longitudinal impacts of SCI on the PK of riluzole are characterized. A time-varying population PK model of riluzole is established, incorporating time-varying clearance and volume of distribution from combined data of Phase I and Phase II/III trials. With the developed model, a rational, optimal dosing scheme can be designed with time-dependent modification to preserve the required therapeutic exposure of riluzole. The PD of riluzole and the relationship between PK and neurological outcomes of the treatment were established. The time course of efficacy in total motor score improvement (ΔTMS) and pNF-H were monitored. A three-dimensional (3D) PK/PD correlation was established for ΔTMS at 6 months with overall riluzole exposure area under the curve for Day 0-Day14 (AUCD0-D14) and baseline TMS for individual patients. Patients with baseline TMS between 1 and 36 benefited from the optimal exposure range of 16-48 mg*h/mL. The PD models of pNF-H revealed the riluzole efficacy, as treated subjects exhibited a diminished increase in progression of pNF-H, indicative of reduced axonal breakdown. The independent parameter of area between effective curves (ABEC) between the time profiles of pNF-H in placebo and treatment groups was statistically identified as a significant predictor for the treatment effect on the biomarker. A mechanistic clinical outcomes (CO)/PD (pNF-H) model was established, and the proposed structure demonstrated the feasibility of PK/PD/CO correlation model. No appreciable hepatic toxicity was observed with the current riluzole treatment regimen. The development of effective treatment for SCI is challenging. However, the future model-informed and PK-guided drug development and regimen modification can be rationally executed with the optimal dosing regimen design based on the developed 3D PK/PD model. The PK/PD/CO model can serve as a rational guide for future drug development, PKPD model refinement, and extension to other studies in SCI settings.

Dynein-Powered Cell Locomotion Guides Metastasis of Breast Cancer.

Metastasis is a principal cause of death in cancer patients, which remains an unresolved fundamental and clinical problem. Conventionally, metastatic dissemination is linked to the actomyosin-driven cell locomotion. However, locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, we identify a complementary mechanism of metastatic locomotion powered by the dynein-generated forces. These forces that arise within a non-stretchable microtubule network drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. We also show that dynein-powered locomotion becomes indispensable during invasive 3D migration within a tissue-like luminal network between spatially confining hydrogel microspheres. Our results indicate that the complementary contractile system of dynein motors and microtubules is always necessary and in certain instances completely sufficient for dissemination of metastatic breast cancer cells. These findings advance fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis.

Examining the Vietnamese Montreal cognitive assessment in healthy and moderate-to-severe traumatic brain injury populations.

Objective: There have been attempts to modify the Montreal Cognitive Assessment (MoCA), a brief cognitive screening tool, for use across several Asian countries, but evidence to support the utility of these translations has been limited, particularly for the Vietnamese translation of the MoCA (MoCA-V). This two-part study aimed to evaluate the MoCA-V in a Vietnamese sample. Methods: In the first stage, we examined the relationships between the MoCA-V subscales and common neuropsychological tests among healthy Vietnamese adults (n = 129) and individuals with moderate-to-severe traumatic brain injury (n = 80). In the second stage, we explored the relationship of TBI status (TBI vs non-TBI) and demographic variables to MoCA-V performance and investigated the optimal cut-off score of the MoCA-V using the two samples combined. Results: The MoCA-V Attention, Language, and Executive Function subscales were correlated with the Digit Span Test, Verbal Fluency Test, and Trail Making Test, respectively, across healthy participants and participants with TBI. Global performance on the MoCA-V was predicted by TBI status, education, and age. Our ROC analysis revealed that a cut-off score of 22 offered the best sensitivity (76.3%) and specificity (71.3%) trade-off for identifying cognitive impairment as measured by the MoCA-V. Conclusions: In addition to identifying a cut-off score for cognitive screening, the findings provide support for the validity of the examined MoCA-V subscales and for the MoCA-V's ability to distinguish TBI survivors vs controls. These results may pave the way for larger-scale investigations of the MoCA-V and for the development of more neuropsychological batteries in Vietnamese.

Continuing education in diversity and multicultural factors: Current state psychology board requirements and a call to action.

Objective: A growing body of literature shows the unequivocal importance of incorporating diversity-related factors into the practice of clinical neuropsychology. Thus, it is imperative that we continue to seek and obtain updated training and knowledge on how culture and diversity intersect with our clinical roles throughout our careers, not merely to satisfy initial coursework requirements. Although most professional organizations pertaining to clinical psychology - and thereby neuropsychology - strongly encourage the pursuit of training in diversity-related factors, explicit requirements for such training across one's career are minimal. Method: The Asian Neuropsychological Association Advocacy Committee reviewed continuing education (CE) requirements for all US states. Results: We found that only 8 states mandated CE credits pertaining to diversity-related factors for the renewal of licensure. Discussion: Given how inseparable cultural competence is from any aspect of clinical work (and the harm that can be done if culture is not considered), it is essential that our field shift from aspirational guidance to firm requirements with regard to cultural competence and diversity-related training in psychology. Requiring CE units devoted to diversity-related factors represents one avenue to pursue this goal. This commentary outlines the current status of diversity-related CE for psychology licensure renewal and offers future directions for incorporating such training as a part of continuing professional development and education.

Second Gamma Knife Treatment for Trigeminal Neuralgia: Anterior Target Spacing and 25 Gy as the Second Dose.

Objective Gamma Knife® radiosurgery (GKRS) has been demonstrated to be a well-known approach for treating patients with medical refractory trigeminal neuralgia (TN). Herein, the authors review the outcomes of pain among a large cohort of patients who had undergone a second GKRS delivered at a significantly reduced dose. Methods The authors conducted a prospective analysis of patients who have undergone two GKRS procedures between the years 2012 to 2021 at one institution. Baseline characteristics, radiosurgical dosimetry and technique, pain outcomes, and adverse effects were reviewed. Pain outcomes were measured with the Barrow Neurological Institute (BNI) pain intensity scale, which included the best BNI attained after the last treatment and recurrence. Results A total of 202 patients were identified, including 55 males and 147 females. Pain recurrence was reported in all patients prior to the second GKRS treatment (median = 4 months). Pain recurrence in the preceding Japan Neuroscience Society (JNS) 2021 study was also reported in all patients after each GKRS with a median value of 20 months between the second and third procedures. Complete to partial pain relief (BNI ≤ III) was achieved in 80% of patients after the second treatment. Over a median of 12 months of follow-up, 60% of patients maintained complete to partial pain relief compared to 77% of patients over the course of three treatments. In the present study, one patient developed facial spasms while 10 patients experienced persistent facial tingling. Subjective mild numbness was also found to be present in 16% of patients, with only 2% being bothersome, as compared to the JNS study, where subjective mild numbness was found to be present in 14%, with only 14.3% being bothersome. Among the 202 patients, 74 (37%) patients had undergone subsequent additional procedures such as a third GKRS, microvascular decompression (MVD), or other percutaneous procedures. Conclusion The authors describe the largest study to date of patients undergoing a second GKRS treatment for type 1 medical refractory trigeminal neuralgia. A reduced dose of radiation for a second treatment may produce outcomes similar to those of three consecutive treatments in regard to limiting recurrence and adverse effects.