Superficial versus deep lymph node dissection in early stage vulvar carcinoma

Our primary objective was to evaluate the difference in overall survival, recurrence rate, and post-operative morbidity related to superficial versus deep inguinal lymphadenectomy in squamous cell carcinoma of the vulva

Inhibition of DUSP6 sensitizes ovarian cancer cells to chemotherapeutic agents via regulation of ERK signaling response genes

Dual specificity phosphatase 6 (DUSP6) is a protein phosphatase that deactivates extracellular-signal-regulated kinase (ERK). Since the ovarian cancer biomarker human epididymis protein 4 (HE4) interacts with the ERK pathway, we sought to determine the relationship between DUSP6 and HE4 and elucidate DUSP6’s role in epithelial ovarian cancer (EOC). Viability assays revealed a significant decrease in cell viability with pharmacological inhibition of DUSP6 using (E/Z)-BCI hydrochloride in ovarian cancer cells treated with carboplatin or paclitaxel, compared to treatment with either agent alone. Quantitative PCR was used to evaluate levels of ERK pathway response genes to BCI in combination with recombinant HE4 (rHE4), carboplatin, and paclitaxel. Expression of EGR1, a promoter of apoptosis, was higher in cells co-treated with BCI and paclitaxel or carboplatin than in cells treated with chemotherapeutic agents alone, while expression of the proto-oncogene c-JUN was decreased with co-treatment. The effect of BCI on the expression of these two genes opposed that of rHE4. Pathway focused quantitative PCR also revealed suppression of ERBB3 in cells co-treated with BCI plus carboplatin or paclitaxel. Finally, expression levels of DUSP6 in EOC tissue were evaluated by immunohistochemistry, revealing significantly increased levels of DUSP6 in serous EOC tissue compared to adjacent normal tissue. A positive correlation between HE4 and DUSP6 levels was determined by Spearman Rank correlation. In conclusion, DUSP6 inhibition sensitizes ovarian cancer cells to chemotherapeutic agents and alters gene expression of ERK response genes, suggesting that DUSP6 could plausibly function as a novel therapeutic target to reduce chemoresistance in EOC

New Pleistocene cave faunas of the Andes of central Peru : radiocarbon ages and the survival of low latitude pleistocene DNA

Peruvian citizens have led our team to their discoveries of Pleistocene cave faunas in the central Andes of Per. These caves (Jatun Uchco, Departamento de Huanuco; Cueva Rosello, Departamento de Junin; and Trigo Jirka, Departamento de Huanuco) preserve numerous carnivorans (Puma, a sabercat [Smilodon populator], an unnamed large extinct felid, fox [Lycalopex sp.], hognose skunk [Conepatus sp.]), deer (cf. Pudu and cf. Hippocamelus), vicuna, an extinct horse (dagger Onohippidium devillei), a chinchillid rodent (cf. Lagidium), bats (Anoura, Desmodus, and Platalina), and sloths (dagger Megatherium, dagger Scelidodon, and, dagger Diabolotherium). Bats were found only in the lowest cave (Jatun Uchco, 2,150 m), and ungulates were found only at Cueva Rosello-the only cave studied in a region of flat terrain. Trigo Jirka preserved ancient feces of a large animal and the keratin claw of dagger Diabolotherium. Collagen for radiocarbon dating and DNA for phylogenetic studies have been isolated from bone from Cueva Rosello (3,875 m) and Trigo Jirka (2,700 m). Conventional radiometric ages from Cueva Rosello are 23,340 +/- 120 and 22,220 +/- 130 years before present and that of Trigo Jirka is 29,140 +/- 260. Ancient DNA (aDNA) from dagger Onohippidium of Cueva Rosello (12 degrees South latitude) and dagger Diabolotherium of Trigo Jirka (10 degrees South) is being used in phylogenetic studies. The successful recovery of aDNA suggests that the cool temperatures, low humidity, and the shield from UV radiation of caves at high elevation can permit aDNA studies at low latitudes. Previously, such studies have been limited to latitudes greater than 35 degrees for Pleistocene samples

Gynecologic Surgical Outcomes Through the Patient\u27s Eyes: Are Physicians Looking in the Same Direction?

Importance: Patient-centered care integrates the highest clinical standards with patient preferences surrounding their treatment. Increasing focus is being placed on the identification of patient-centered outcomes to optimize the impact of medical treatments on patient quality of life, as defined by patients themselves. Objective: This article will review the central concepts of patient-centered outcomes in benign gynecologic surgery. This expert review will serve as a practical guide for surgeons to incorporate patient preferences into shared surgical decision making. Evidence Acquisition: The current literature is examined, defining those outcomes identified by women undergoing gynecologic procedures as the most important factors in their decision making. Available literature on these patient-identified priorities is then reviewed with respect to gynecologic surgery in the preoperative, intraoperative, and postoperative periods. Results: Each section of the article concludes with Clinical Pearls, where practical tools and key elements are summarized to assist providers with incorporating these concepts into practice. Conclusions and Relevance: Many key outcomes have been identified by women undergoing benign gynecologic surgery in their decision-making process. Patient counseling should address clinically appropriate treatment modalities and include an exploration of patient expectations and preferences around nonclinical outcomes as well. This shared decision-making model will result in improved satisfaction with outcomes

43 Severe maternal morbidity is increased among pregnant persons with gynecological malignancies

Objectives: In this study, we sought to examine whether pregnant individuals diagnosed with a gynecologic malignancy experienced higher rates of severe maternal morbidity (SMM). Methods: This was a retrospective cohort study of deliveries at 23 to 42 weeks of gestation in California between the years of 2007 and 2011. Gynecologic malignancies included uterine, ovarian, cervix, and vulvar cancer. SMM was defined using an already published algorithm. Potential confounders included race/ethnicity, maternal age, body mass index, education level, insurance status, parity, smoking history and number of prenatal visits. Chi-square and multivariable logistic regression analyses were performed for statistical comparisons. Results: In the cohort of 3,153,851 a total of 981 (0.03%) deliveries impacted by a gynecologic cancer diagnosis were identified. SMM was approximately 3 times more common in pregnancies impacted by a gynecologic malignancy (4.33%) compared to those that were not (1.12%), with an odds ratio of 3.86 (95% CI: 2.74–5.45). The odds of SMM was highest among Black individuals with gynecologic malignancy compared to all other racial/ethnic groups (aOR 2.03, 95% CI: 1.94–2.13). When examining the conditions driving the increase in SMM, we found that hysterectomy (aOR 27.04, 95% CI: 17.60–41.52) and blood transfusion (aOR 2.3, 95% CI: 1.44–3.67) were occurring more frequently. Conclusions: The risk of SMM is significantly higher among pregnant individuals with gynecologic malignancies. Within this population, Black pregnant people experienced the highest risk of SMM relative to all other racial/ethnic groups. More work is required to address on-going racial disparities and to optimize outcomes for all pregnant individuals with gynecologic cancer diagnoses

Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia

Mindfulness meditation reduces pain in experimental and clinical settings. However, it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect (e.g., conditioning, psychosocial context, beliefs). To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo, we randomly assigned 75 healthy, human volunteers to 4 d of the following: (1) mindfulness meditation, (2) placebo conditioning, (3) sham mindfulness meditation, or (4) book-listening control intervention. We assessed intervention efficacy using psychophysical evaluation of experimental pain and functional neuroimaging. Importantly, all cognitive manipulations (i.e., mindfulness meditation, placebo conditioning, sham mindfulness meditation) significantly attenuated pain intensity and unpleasantness ratings when compared to rest and the control condition (p < 0.05). Mindfulness meditation reduced pain intensity (p = 0.032) and pain unpleasantness (p < 0.001) ratings more than placebo analgesia. Mindfulness meditation also reduced pain intensity (p = 0.030) and pain unpleasantness (p = 0.043) ratings more than sham mindfulness meditation. Mindfulness-meditation-related pain relief was associated with greater activation in brain regions associated with the cognitive modulation of pain, including the orbitofrontal, subgenual anterior cingulate, and anterior insular cortex. In contrast, placebo analgesia was associated with activation of the dorsolateral prefrontal cortex and deactivation of sensory processing regions (secondary somatosensory cortex). Sham mindfulness meditation-induced analgesia was not correlated with significant neural activity, but rather by greater reductions in respiration rate. This study is the first to demonstrate that mindfulness-related pain relief is mechanistically distinct from placebo analgesia. The elucidation of this distinction confirms the existence of multiple, cognitively driven, supraspinal mechanisms for pain modulation. SIGNIFICANCE STATEMENT Recent findings have demonstrated that mindfulness meditation significantly reduces pain. Given that the “gold standard” for evaluating the efficacy of behavioral interventions is based on appropriate placebo comparisons, it is imperative that we establish whether there is an effect supporting meditation-related pain relief above and beyond the effects of placebo. Here, we provide novel evidence demonstrating that mindfulness meditation produces greater pain relief and employs distinct neural mechanisms than placebo cream and sham mindfulness meditation. Specifically, mindfulness meditation-induced pain relief activated higher-order brain regions, including the orbitofrontal and cingulate cortices. In contrast, placebo analgesia was associated with decreased pain-related brain activation. These findings demonstrate that mindfulness meditation reduces pain through unique mechanisms and may foster greater acceptance of meditation as an adjunct pain therapy

Telehealth-delivered naturalistic developmental behavioural intervention with and without caregiver acceptance and commitment therapy for autistic children and their caregivers: protocol for a multi-arm parallel group randomised clinical trial

Introduction Timely access to early support that optimises autistic children’s development and their caregiver’s mental health is critical. Naturalistic developmental behavioural interventions (NDBIs) and acceptance and commitment therapy (ACT) are evidence-based supports that can enhance child learning and behaviour, and adult well-being, respectively. The traditional face-to-face delivery of these approaches is resource intensive. Further, little is known about the benefit of parallel child-focused and caregiver-focused supports. The aims of this trial are to evaluate the effectiveness and social validity of telehealth-delivered, caregiver-implemented, child-focused NDBI and caregiver-focused ACT when delivered alone and in parallel, on autistic children’s social communication and caregiver well-being.Methods and analysis The study will use a randomised, single-blind clinical trial with three parallel arms: NDBI; ACT and ACT+NDBI. We will recruit a minimum of 78, 2–5-year-old autistic children and their families throughout Aotearoa New Zealand. Support will be delivered over 13 weeks using a combination of culturally enhanced web-based modules and online group coaching. Primary outcome variables include children’s social communication/engagement with their caregiver as well as caregiver stress and will be evaluated using a repeated measures multivariate analysis of variance. Outcome variables are assessed at baseline (before randomisation), immediately postparticipation and at 3-month follow-up.Ethics and dissemination The trial is approved by the Health and Disability Ethics Committee (2022 FULL 12058). The findings of this trial will be disseminated through peer-reviewed journals and national and international conference proceedings regardless of the magnitude/direction of effect. Additionally, data will be shared with stakeholder groups, service providers and health professionals.Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12622001134718)