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Abstract Context Secondary adrenal insufficiency is a potential complication of transsphenoidal adenomectomy (TSA). Most centers test recovery of the hypothalamo-pituitary-adrenal (HPA) axis after TSA, but, to our knowledge, there are no data predicting likelihood of recovery or the frequency of later recovery of HPA function. Objective To assess timing and predictors of HPA axis recovery after TSA. Design Single-center, retrospective analysis of consecutive pituitary surgeries performed between February 2015 and September 2018. Patients Patients (N = 109) with short Synacthen test (SST) data before and at sequential time points after TSA. Main outcome measures Recovery of HPA axis function at 6 weeks, and 3, 6, and 9 to12 months after TSA. Results Preoperative SST indicated adrenal insufficiency in 21.1% Among these patients, 34.8% recovered by 6 weeks after TSA. Among the 65.2% (n = 15) remaining, 13.3% and 20% recovered at 3 months and 9 to 12 months, respectively. Of the 29% of patients with adrenal insufficiency at the 6-week SST, 16%, 12%, and 6% subsequently recovered at 3, 6, and 9 to 12 months, respectively. Preoperative SST 30-minute cortisol, postoperative day 8 cortisol, and 6-week postoperative SST baseline cortisol levels above or below 430 nmol/L [15.5 μg/dL; AUC ROC, 0.86]; 160 nmol/L (5.8 μg/dL; AUC ROC, 0.75); and 180 nmol/L (6.5 μg/dL; AUC ROC, 0.88), were identified as cutoffs for predicting 6-week HPA recovery. No patients with all three cutoffs below the threshold recovered within 12 months after TSA, whereas 92% with all cutoffs above the threshold recovered HPA function within 6 weeks (OR, 12.200; 95% CI, 5.268 to 28.255). Conclusion HPA axis recovery can occur as late as 9 to 12 months after TSA, demonstrating the need for periodic reassessment of patients who initially have SST-determined adrenal insufficiency after TSA. Pre- and postoperative SST values can guide which patients are likely to recover function and potentially avoid unnecessary lifelong glucocorticoid replacement. After TSA, pre- and postoperative SST cortisol levels can predict 6-week HPA axis recovery. Recovery occurs even 12 months after TSA, demonstrating the need for periodic retesting.

Background Hypopituitarism is a potential sequelea of pituitary macroadenoma or trans-sphenoidal adenomectomy (TSA). Recovery of pituitary function can occur post-TSA, and reassessment is required to avoid needless hormonal replacement. The timing and frequency of re-testing is variable across centres and the aim of this study was to determine rate of, and time to recovery of hypothalamic-pituitary adrenal (HPA), gonadal and thyroid axes postTSA. Methods We performed a single-centre retrospective analysis of TSA patients from February 2015 to September 2018. Patients with apoplexy, corticotroph adenomas, redo-surgery, emergency TSA, craniotomy or pituitary radiotherapy were excluded. Thyroid, gonadal and HPA axis adequacy was respectively assessed with TSH/freeT4, FSH/LH/estradiol or testosterone measurement and short synacthen test (SST), performed pre-TSA and at 6-weeks, 3-, 6-, and 9 to 12-months post-TSA. Results Data on 135 patients (mean age 54±17 years; 80M) were analysed. Macroadenomas occurred in 118 (87.4%), microadenoma in 8 (5.9%). Histology confirmed gonadotroph (53%), somatotroph (10.4%), plurihormonal (13.3%), lactotroph (5.2%), meningioma (1.5%), craniopharyngioma (12.6%), thyrotroph (1.5%) and metastatic malignancy (2.2%). 53.7%, 30.2% and 19.1% of patients had pre-op gonadal, thyroid and HPA function deficit respectively. 59% of patients had at least one deficit at baseline. Age was associated with the number of deficits manifested (F=6.026, p<0.001). 6-weeks post-TSA, 31.4%, 20.6% and 32% showed gonadal, thyroid and HPA axis deficit respectively. 35.7% of patients with normal pre-op pituitary function developed at least one new hormonal axis deficit at 6-weeks. Of 19.1% patients with abnormal pre-op HPA function, 30.4 % (7/23) recovered at 6-weeks. Among patients with abnormal HPA function at 6 weeks, 12.2%, 7.3% and 4.9% recovered at 3-, 6-, and 9 to 12-months respectively. 31.6% of patients with abnormal pre-op thyroid and 20% of patients with abnormal pre-op gonadal axes recovered at 6-weeks. Among patients recovering HPA axis function at 6-weeks, the majority also recovered thyroid axis (85.1% vs 14.9%, χ2=4.839, OR 2.643, p=0.03), whereas no association was found between gonadal and HPA axis recovery (54.1% vs 45.9%, p=0.16). Conclusions We demonstrate a significant rate of recovery of pre-operative pituitary deficit following TSA. 6-weeks post-operatively, gonadal failure is the most prevalent deficit. Regaining HPA axis function is a positive predictor for thyroid axis recovery but not gonadal axis recovery. HPA axis normalization can even occur at 9 to 12-months post-TSA, emphasizing the importance of periodic reassessment to avoid unnecessary hydrocortisone replacement in those who could eventually regain function. More longitudinal data are needed to assess the potential for recovery of thyroid and gonadal axes at >6 weeks post-op.

The mechanisms that lead to variation in human skin and hair color are not fully understood. To better understand the molecular control of skin and hair color variation, we modulated the expression of Tyrosinase (Tyr), which controls the rate-limiting step of melanogenesis, by expressing a single-copy, tetracycline-inducible shRNA against Tyr in mice. Moderate depletion of TYR was sufficient to alter the appearance of the mouse coat in black, agouti, and yellow coat color backgrounds, even though TYR depletion did not significantly inhibit accumulation of melanin within the mouse hair. Ultra-structural studies revealed that the reduction of Tyr inhibited the accumulation of terminal melanosomes, and inhibited the expression of genes that regulate melanogenesis. These results indicate that color in skin and hair is determined not only by the total amount of melanin within the hair, but also by the relative accumulation of mature melanosomes.

Background: The literature alludes to several studies highlighting challenges with human proxy as decision makers such as emotional burden, physician barriers, decisional conflict, accuracy, and overconfidence. However, only a small subset reported on a proxy's congruency. This study expanded on a proof-of-concept that artificial intelligence (AI) can act as a proxy decision maker with value preferences and considered its ethical implications. Aim: To compare the congruency of AI as a proxy decision maker with human proxies on end-of-life treatment decisions. Methods: Utilizing LLaMa3, an AI Large Language Model as a proxy decision tool, we recruited 15 adults and their legal decision makers as dyads to complete a value and end-of-life preference surveys for a comparison analysis. We measured the participants' overall composite value scores and collected their end-of-life preferences to use in the AI congruence evaluation. Congruency percentage was taken over three clinical hypothetical scenarios and compared between the participant with either the human or AI proxy. Results: The mean congruency percentage between the participant and human proxy was 44.4% (95% CI: 23.6-65.3), n = 12. Fifty percent of dyads had one or no matching responses across the three scenarios and 16% had perfectly matched responses. After the model's adjustment for prompt engineering and parameter fine-tuning, the congruency with AI and value inputs was 72.2% (95% CI: 67.4-77.0) with 67.0% matched responses. The model performed the same as the human proxy without value preferences with congruency of 45.3% (95% CI: 36.2-54.4). Discussion: The AI model had a 28% higher congruency as a proxy decision-maker for end-of-life treatment decisions after the inclusion of value preferences. This approach has a promising utility as a supplemental tool for human decision-making and can protect self -determination if values are pre-recorded in the event of decisional incapacity.

Abstract Introduction Patients with advanced cancer and their spousal caregivers who parent minor children report unmet parenting concerns and increased psychological distress. Seeking to address these important supportive care needs, this RCT examined the feasibility, acceptability, and initial evidence for the efficacy of a novel psychosocial intervention. Patients and Methods Patients with a metastatic solid malignancy and their spouses completed self-reported validated assessments of psychological symptoms and cancer-related parenting outcomes and were then randomized to the parent support intervention or a usual care (UC) group. Both groups were reassessed 6 and 12 weeks later. Dyads randomized to the counselor-led intervention attended the first 2 sessions jointly addressing illness communication and family routines. Spouses individually attended the last 2 sessions focusing on caregiver support and family death preparedness. Results Fifty patients and their spouses were randomized. All a priori feasibility benchmarks were met. Attendance in the intervention arm was high with 84% of caregivers attending all 4 sessions (mean = 3.48). The program was evaluated favorably by all patients and spouses deeming the intervention as beneficial. Caregivers rated the individual-level sessions as particularly helpful. Multilevel analyses revealed a significant reduction in anxiety symptoms (P = .05) and improvement in parenting efficacy (P = .03) at 6-week follow-up in the intervention group compared with UC. Conclusions The initial testing of our parent support intervention yielded promising results regarding feasibility and preliminary evidence for efficacy for reduced anxiety symptoms and improved parenting efficacy. This program may meet a frequent and distressing psychosocial need that is typically unaddressed by multidisciplinary oncology teams.

Weeds are attractive models for basic and applied research due to their impacts on agricultural systems and capacity to swiftly adapt in response to anthropogenic selection pressures. Currently, a lack of genomic information precludes research to elucidate the genetic basis of rapid adaptation for important traits like herbicide resistance and stress tolerance and the effect of evolutionary mechanisms on wild populations. The International Weed Genomics Consortium is a collaborative group of scientists focused on developing genomic resources to impact research into sustainable, effective weed control methods and to provide insights about stress tolerance and adaptation to assist crop breeding.

The influx of international debris, especially plastic, has emerged as a significant environmental challenge for coastal ecosystems. Our study on Cozumel Island (Mexico) investigated the origin and distribution of plastic debris across nine beaches, considering factors such as wind patterns and ocean currents. Results revealed that over 90% of the waste, for which provenance could be confirmed, originated from outside the island, reflecting the global nature of marine pollution. High densities of plastic debris were found on windward beaches, with waste originating from at least 25 countries. This study underscores the pressing need for international cooperation and sustainable waste management strategies to mitigate the environmental impact of marine debris on Cozumel and similar regions. Effective policies combining ecological preservation and sustainable tourism are crucial for addressing the international issue of plastic pollution and safeguarding coastal ecosystems worldwide.