Acupuncture vs Massage for Pain in Patients Living With Advanced Cancer: The IMPACT Randomized Clinical Trial.

Importance: Pain is challenging for patients with advanced cancer. While recent guidelines recommend acupuncture and massage for cancer pain, their comparative effectiveness is unknown. Objective: To compare the effects of acupuncture and massage on musculoskeletal pain among patients with advanced cancer. Design, Setting, and Participants: A multicenter pragmatic randomized clinical trial was conducted at US cancer care centers consisting of a northeastern comprehensive cancer center and a southeastern cancer institute from September 19, 2019, through February 23, 2022. The principal investigator and study statisticians were blinded to treatment assignments. The duration of follow-up was 26 weeks. Intention-to-treat analyses were performed (linear mixed models). Participants included patients with advanced cancer with moderate to severe pain and clinician-estimated life expectancy of 6 months or more. Patient recruitment strategy was multipronged (eg, patient database queries, mailings, referrals, community outreach). Eligible patients had English or Spanish as their first language, were older than 18 years, and had a Karnofsky score greater than or equal to 60 (range, 0-100; higher scores indicating less functional impairment). Interventions: Weekly acupuncture or massage for 10 weeks with monthly booster sessions up to 26 weeks. Main Outcomes and Measures: The primary end point was the change in worst pain intensity score from baseline to 26 weeks. The secondary outcomes included fatigue, insomnia, and quality of life. The Brief Pain Inventory (range, 0-10; higher numbers indicate worse pain intensity or interference) was used to measure the primary outcome. The secondary outcomes included fatigue, insomnia, and quality of life. Results: A total of 298 participants were enrolled (mean [SD] age, 58.7 [14.1] years, 200 [67.1%] were women, 33 [11.1%] Black, 220 [74.1%] White, 46 [15.4%] Hispanic, and 78.5% with solid tumors). The mean (SD) baseline worst pain score was 6.9 (1.5). During 26 weeks, acupuncture reduced the worst pain score, with a mean change of -2.53 (95% CI, -2.92 to -2.15) points, and massage reduced the Brief Pain Inventory worst pain score, with a mean change of -3.01 (95% CI, -3.38 to -2.63) points; the between-group difference was not significant (-0.48; 95% CI, -0.98 to 0.03; P = .07). Both treatments also improved fatigue, insomnia, and quality of life without significant between-group differences. Adverse events were mild and included bruising (6.5% of patients receiving acupuncture) and transient soreness (15.1% patients receiving massage). Conclusions and Relevance: In this randomized clinical trial among patients with advanced cancer, both acupuncture and massage were associated with pain reduction and improved fatigue, insomnia, and quality of life over 26 weeks; however, there was no significant different between the treatments. More research is needed to evaluate how best to integrate these approaches into pain treatment to optimize symptom management for the growing population of people living with advanced cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT04095234.

Locomotor effects of a fibrosis-based immune response in stickleback fish.

The vertebrate immune system provides an impressively effective defense against parasites and pathogens. However, these benefits must be balanced against a range of costly side-effects including energy loss and risks of auto-immunity. These costs might include biomechanical impairment of movement, but little is known about the intersection between immunity and biomechanics. Here, we show that a fibrosis immune response to Schistocephalus solidus infection in freshwater threespine stickleback (Gasterosteus aculeatus) has collateral effects on their locomotion. Although fibrosis is effective at reducing infection, some populations of stickleback actively suppress this immune response, possibly because the costs of fibrosis outweigh the benefits. We quantified the locomotor effects of the fibrosis immune response in the absence of parasites to investigate whether there are incidental costs of fibrosis that could help explain why some fish forego this effective defense. To do this, we induced fibrosis in stickleback and then tested their C-start escape performance. Additionally, we measured the severity of fibrosis, body stiffness and body curvature during the escape response. We were able to estimate performance costs of fibrosis by including these variables as intermediates in a structural equation model. This model revealed that among control fish without fibrosis, there is a performance cost associated with increased body stiffness. However, fish with fibrosis did not experience this cost but rather displayed increased performance with higher fibrosis severity. This result demonstrates that the adaptive landscape of immune responses can be complex with the potential for wide-reaching and unexpected fitness consequences.

Locomotor effects of a fibrosis-based immune response in stickleback fish.

The vertebrate immune system provides an impressively effective defense against parasites and pathogens. However, these benefits must be balanced against a range of costly side-effects including energy loss and risks of auto-immunity. These costs might include biomechanical impairment of movement, but little is known about the intersection between immunity and biomechanics. Here, we show that a fibrosis immune response in threespine stickleback (Gasterosteus aculeatus) has collateral effects on their locomotion. When freshwater stickleback are infected with the tapeworm parasite Schistocephalus solidus, they face an array of fitness consequences ranging from impaired body condition and fertility to an increased risk of mortality. To fight the infection, some stickleback will initiate a fibrosis immune response in which they produce excess collagenous tissue in their coelom. Although fibrosis is effective at reducing infection, some populations of stickleback actively suppress this immune response, possibly because the costs of fibrosis outweigh the benefits. Here we quantify the locomotor effects of the fibrosis immune response in the absence of parasites to investigate whether there are collateral costs of fibrosis that could help explain why some fish forego this effective defense. To do this, we induce fibrosis in stickleback and then test their C-start escape performance. Additionally, we measure the severity of fibrosis, body stiffness, and body curvature during the escape response. We were able to estimate performance costs of fibrosis by including these variables as intermediates in a structural equation model. This model reveals that among control fish without fibrosis, there is a performance cost associated with increased body stiffness. However, fish with fibrosis did not experience this cost but rather displayed increased performance with higher fibrosis severity. This result demonstrates that the adaptive landscape of immune responses can be complex with the potential for wide reaching and unexpected fitness consequences.

Telehealth-Based Music Therapy Versus Cognitive Behavioral Therapy for Anxiety in Cancer Survivors: Rationale and Protocol for a Comparative Effectiveness Trial.

BACKGROUND: Cancer survivors represent one of the fastest growing populations in the United States. Unfortunately, nearly 1 in 3 survivors experience anxiety symptoms as a long-term consequence of cancer and its treatment. Characterized by restlessness, muscle tension, and worry, anxiety worsens the quality of life; impairs daily functioning; and is associated with poor sleep, depressed mood, and fatigue. Although pharmacological treatment options are available, polypharmacy has become a growing concern for cancer survivors. Music therapy (MT) and cognitive behavioral therapy (CBT) are evidence-based, nonpharmacological treatments that have demonstrated effectiveness in treating anxiety symptoms in cancer populations and can be adapted for remote delivery to increase access to mental health treatments. However, the comparative effectiveness of these 2 interventions delivered via telehealth is unknown. OBJECTIVE: The aims of the Music Therapy Versus Cognitive Behavioral Therapy for Cancer-related Anxiety (MELODY) study are to determine the comparative effectiveness of telehealth-based MT versus telehealth-based CBT for anxiety and comorbid symptoms in cancer survivors and to identify patient-level factors associated with greater anxiety symptom reduction for MT and CBT. METHODS: The MELODY study is a 2-arm, parallel-group randomized clinical trial that aims to compare the effectiveness of MT versus CBT for anxiety and comorbid symptoms. The trial will enroll 300 English- or Spanish-speaking survivors of any cancer type or stage who have experienced anxiety symptoms for at least 1 month. Participants will receive 7 weekly sessions of MT or CBT delivered remotely via Zoom (Zoom Video Communications, Inc) over 7 weeks. Validated instruments to assess anxiety (primary outcome), comorbid symptoms (fatigue, depression, insomnia, pain, and cognitive dysfunction), and health-related quality of life will be administered at baseline and at weeks 4, 8 (end of treatment), 16, and 26. Semistructured interviews will be conducted at week 8 with a subsample of 60 participants (30 per treatment arm) to understand individual experiences with the treatment sessions and their impact. RESULTS: The first study participant was enrolled in February 2022. As of January 2023, 151 participants have been enrolled. The trial is expected to be completed by September 2024. CONCLUSIONS: This study is the first and largest randomized clinical trial to compare the short- and long-term effectiveness of remotely delivered MT and CBT for anxiety in cancer survivors. Limitations include the lack of usual care or placebo control groups and the lack of formal diagnostic assessments for psychiatric disorders among trial participants. The study findings will help guide treatment decisions for 2 evidence-based, scalable, and accessible interventions to promote mental well-being during cancer survivorship. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46281.

Addressing cancer-related fatigue through sleep: A secondary analysis of a randomized trial comparing acupuncture and cognitive behavioral therapy for insomnia.

Background: Fatigue is a troublesome symptom in cancer survivors that often results from disrupted sleep. We sought to assess whether two insomnia-focused non-pharmacological interventions are also effective for improving fatigue. Methods: We analyzed data from a randomized clinical trial comparing cognitive behavioral therapy for insomnia (CBT-I) versus acupuncture for insomnia among cancer survivors. Participants were 109 patients who reported insomnia and moderate or worse fatigue. Interventions were delivered over eight weeks. Fatigue was evaluated at baseline, week 8, and week 20 using the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). We used both mediation analysis and t-tests to explore the extent to which fatigue reduction was attributable to insomnia response. Results: Compared to baseline, both CBT-I and acupuncture produced significant reductions in total MFSI-SF scores at week 8 (-17.1 points; 95% confidence interval [CI]: -21.1 to -13.1, and -13.2 points; 95% CI: -17.2 to -9.2, respectively, all p<0.001) and week 20 (-14.6 points; 95% CI: -18.6 to -10.6, and -14.2 points; 95% CI: -18.1 to -10.3. respectively, all p<0.001), with no significant between-group differences. MFSI-SF total scores at week 8 were significantly associated with sleep improvements in both CBT-I and acupuncture groups (p<0.001 and p=0.011, respectively). Insomnia responders demonstrated significantly greater improvements in mean MFSI-SF total scores compared with non-responders in the CBT-I group (p=0.016) but not in the acupuncture group. Conclusion: CBT-I and acupuncture produced similar, clinically meaningful, and durable fatigue reductions in cancer survivors with insomnia, primarily through improvements in sleep. Acupuncture may also reduce fatigue through additional pathways.

Dermal Denticle Diversity in Sharks: Novel Patterns on the Interbranchial Skin.

Shark skin is covered in dermal denticles-tooth-like structures consisting of enameloid, dentine, and a central pulp cavity. Previous studies have demonstrated differences in denticle morphology both among species and across different body regions within a species, including one report of extreme morphological variation within a 1 cm distance on the skin covering the branchial pouches, a region termed "interbranchial skin." We used gel-based profilometry, histology, and scanning electron microscopy to quantify differences in denticle morphology and surface topography of interbranchial skin denticles among 13 species of sharks to better understand the surface structure of this region. We show that (1) interbranchial skin denticles differ across shark species, and (2) denticles on the leading edge of the skin covering each gill pouch have different morphology and surface topography compared with denticles on the trailing edge. Across all species studied, there were significant differences in denticle length (P = 0.01) and width (P = 0.002), with shorter and wider leading edge denticles compared with trailing edge denticles. Surface skew was also higher in leading edge denticles (P = 0.009), though most values were still negative, indicating a surface texture more dominated by valleys than peaks. Overall, leading edge denticles were smoother-edged than trailing edge denticles in all of the species studied. These data suggest two hypotheses: (1) smoother-edged leading edge denticles protect the previous gill flap from abrasion during respiration, and (2) ridged denticle morphology at the trailing edge might alter water turbulence exiting branchial pouches after passing over the gills. Future studies will focus on determining the relationship between denticle morphology and water flow by visualizing fluid motion over interbranchial denticles during in vivo respiration.

La piel de los tiburones está cubierta de dentículos dérmicos, estructuras similares a los dientes que constan de un tejido esmaltado, una dentina y una cavidad pulpar central. Estudios anteriores han demostrado diferencias en la morfología de los dentículos tanto entre especies como entre diferentes regiones del cuerpo dentro de una misma especie, incluyendo un informe sobre la extrema variación morfológica dentro de una distancia de 1 cm en la piel que cubre las bolsas branquiales, una región denominada "piel interbranquial." Hemos utilizado perfilometría basada en gel, histología y microscopía electrónica de barrido, para cuantificar las diferencias en la morfología de los dentículos y la topografía de la superficie de la piel interbranquial de los dentículos en 13 especies de tiburones, para comprender mejor la estructura de la superficie de esta región. Demostramos que (1) los dentículos de la piel interbranquial difieren entre las especies de tiburones, y (2) los dentículos del borde anterior de la piel que cubre cada bolsa branquial tienen una morfología y una topografía superficial diferentes en comparación con los dentículos del borde posterior. En todas las especies estudiadas, hubo diferencias significativas en la longitud (P = 0.01) y en el ancho (P = 0.002), con dentículos del borde anterior más cortos y anchos que los del borde posterior. La inclinación de la superficie también era mayor en los dentículos del borde anterior (P = 0.009) aunque la mayoría de los valores seguían siendo negativos, lo que indicaba más valles que picos. En general, los dentículos de la parte anterior tenian los bordes mas lisos que los de la parte posterior en todas las especies estudiadas. Estos datos sugieren dos hipótesis: (1) los dentículos del borde anterior con bordes más lisos protegen la aleta branquial previa de la abrasión durante la respiración, y (2) la morfología de los dentículos con crestas en el borde posterior podría alterar la turbulencia del agua que sale de las bolsas branquiales después de pasar por las branquias. Futuros estudios se centrarán en determinar la relación entre la morfología de los dentículos y el flujo de agua mediante la visualización del movimiento del fluido sobre los dentículos interbranquiales durante la respiración in vivo.Translated by Laura Paez, Ph.D. student­Swiss Federal Institute of Technology Lausanne.

 ìƒì–´ì˜ 비늘은 유법랑질, 상아질, 치수강으로 이루어졌으며, 낱개로 ë³´ë©´ 생김새가 이빨을 닮았다. 기존의 연구에서는 상어 비늘의 형태학적 구조를 종 간 및 동종 내 다른 어체 부위의 다양한 각도에서 분석했는데, ê·¸ 중에서도 아가미구멍 사이의 1cm에 불과한 범위에서 예상 외의 표면미세구조 다양성을 발견한 연구가 주목된다. 상어 비늘의 형태학적 이해를 돕기 위하여, 본 연구에서는 젤을 사용한 프로필로메트리(gel-based profilometry), 조직학적 기법 및 주사전자현미경법을 통하여, 상어류 13종에서 아가미구멍 사이 피부의 비늘 형태와 표면미세구조를 분석했다. 본 연구의 결과는 (1) 아가미구멍 사이 피부의 표면형태에는 종 간 차이가 있고, (2) 아가미구멍 사이 피부의 전방 (머리 방향) 비늘은 후방 (꼬리 방향) 의 비늘에 비하여 훨씬 더 큰 수준의 다양성을 보였다는 것이다. 분석한 13종 모두를 통틀어, 아가미구멍 사이 피부의 전방 비늘은 후방의 비늘 보다 훨씬 넓고 (P = 0.01) ê¸¸ì—ˆë‹¤ (P = 0.002). 본 연구에서는 (1) 부드러운 머리 쪽 비늘이 상어가 숨 쉴 때마다 아가미구멍을 통해 빠져나온 물 흐름의 저항을 줄여준다는 것, 그리고 (2) 꼬리 쪽 가장자리의 비늘에서 두드러지는 들쭉날쭉한 가장자리는 아마도 비슷한 원리에서 아가미구멍을 통해 빠져나온 물의 소용돌이를 줄여 준다는 가설을 세울 수 있었다. 미래의 연구에서는 실험실 내의 조건에서 아가미구멍을 통해 흐르는 물의 역학적인 측면을 상어 비늘의 형태학적 측면과 연관지어 접근해야 할 것이다.Translated by Daemin Kim, Ph.D. student­Yale University.

Die Haut von Haien ist mit dermalen Dentikeln bedeckt - zahnähnlichen Strukturen, die aus Schmelz, Dentin und einer zentralen Pulpahöhle bestehen. Vorhergehende Studien haben Unterschiede in der Morphologie der Dentikel sowohl zwischen den Arten als auch zwischen verschiedenen Körperregionen innerhalb einer Art gezeigt, einschließlich eines Berichts über extreme morphologische Variationen innerhalb eines Abstands von 1 cm auf der Haut, die die Kiementaschen bedeckt, eine Region, die als "Interbranchialhaut" bezeichnet wird. Um die Oberflächenstruktur dieser Region besser zu versteshen, haben wir die Unterschiede in der Morphologie und Oberflächentopographie der Dentikel der Interbranchialhaut in 13 Haiarten mit Hilfe von Gel-Profilometrie, Histologie und Rasterelektronenmikroskopie quantifiziert. Wir konnten zeigen, dass (1) sich die Dentikel der Interbranchialhaut zwischen den Haiarten unterscheiden und (2) die Dentikel an der Vorderkante der Haut, die jede Kiementasche bedeckt, eine andere Morphologie und Oberflächentopographie aufweisen als die Dentikel an der Hinterkante. Bei allen untersuchten Arten gab es signifikante Unterschiede in der Länge (P = 0.01) und Breite (P = 0.002) der Dentikel, wobei die Dentikel an der Vorderkante kürzer und breiter waren als die Dentikel an der Hinterkante. Auch die Oberflächenschiefe war bei den Dentikeln der Vorderkante höher (P = 0.009), obwohl die meisten Werte immer noch negativ waren, was auf mehr Täler als Spitzen hinweist. Insgesamt waren die Vorderkanten-Dentikel bei allen untersuchten Arten glatter als die Hinterkanten-Dentikel. Diese Daten legen zwei Hypothesen nahe: (1) Glattere Vorderkantenzähne schützen den vorhergehenden Kiemenlappen vor Abrieb während der Atmung, und (2) die Morphologie der gezackten Zähne an der Hinterkante könnte die Wasserturbulenz beim Austritt aus den Kiementaschen nach dem Passieren der Kiemen verändern. Zukünftige Studien werden sich darauf konzentrieren, die Beziehung zwischen der Morphologie der Dentikel und der Wasserströmung zu bestimmen, indem die Flüssigkeitsbewegung über die Interbranchialdentikel während der In-vivo-Atmung sichtbar gemacht wird.Translated by Robin Thandiackal, postdoctoral fellow­Harvard University.

La peau des requins est recouverte de denticules dermiques - des structures semblables à des dents composées d'émail, de dentine et d'une cavité pulpaire centrale. Des études précédentes ont démontré que la morphologie des denticules diffère entre les espèces, mais également entre les différentes régions du corps au sein d'une même espèce. Il existe notamment une variation morphologique extrême sur une distance de 1 cm dans la région appelée "peau interbranchiale," soit la peau peau couvrant les poches branchiales. Nous avons utilisé la profilométrie à base de gel, l'histologie et la microscopie électronique à balayage pour quantifier les différences morphologiques et topographiques des denticules de la peau interbranchiale chez 13 espèces de requins, ceci afin de mieux comprendre la structure de la surface de cette région. Nos résultats montrent que (1) les denticules de la peau interbranchiale diffèrent selon les espèces de requins, et (2) les denticules situées sur le bord d'attaque de la peau couvrant chaque poche branchiale ont une morphologie et une topographie de surface différentes de celles des denticules situées sur le bord de fuite. Chez toutes les espèces étudiées, il y avait des différences significatives dans la longueur (P = 0.01) et la largeur (P = 0.002) des denticules, avec les denticules du bord antérieur plus courtes et plus larges que celles du bord postérieur. L'asymétrie de la surface était également plus élevée dans les denticules antérieures (P = 0.009), bien que la plupart des valeurs soient négatives, indiquant plus de vallées que de sommets.Par ailleurs, , les denticules du bord antérieur étaient plus lisses que celles du bord postérieur. Dans l'ensemble, ces données suggèrent deux hypothèses: (1) les denticules situées sur le bord d'attaque et possédant une surface plus lisse protègent le volet branchial précédent de l'abrasion pendant la respiration, et (2) la morphologie plutôt striée des denticules situées sur le bord de fuite pourrait modifier les caractéristiques turbulentes de l'écoulement sortant des poches branchiales après être passé sur les branchies. Les études futures se concentreront sur la détermination de la relation entre la morphologie des denticules et l'écoulement de l'eau en visualisant le mouvement du fluide sur les denticules interbranchiaux pendant la respiration in vivo.Translated by Elsa Goerig, postdoctoral fellow­Harvard University.