Variation in diurnal cortisol patterns among the Indigenous Shuar of Amazonian Ecuador.

OBJECTIVES: The hypothalamic-pituitary-adrenal (HPA) axis and its primary end product, the glucocorticoid cortisol, are major components of the evolved human stress response. However, most studies have examined these systems among populations in high-income settings, which differ from the high pathogen and limited resource contexts in which the HPA axis functioned for most of human evolution. METHODS: We investigated variability in diurnal salivary cortisol patterns among 298 Indigenous Shuar from Amazonian Ecuador (147 males, 151 females; age 2-86 years), focusing on the effects of age, biological sex, and body mass index (BMI) in shaping differences in diurnal cortisol production. Saliva samples were collected three times daily (waking, 30 minutes post-waking, evening) for three consecutive days to measure key cortisol parameters: levels at waking, the cortisol awakening response, the diurnal slope, and total daily output. RESULTS: Age was positively associated with waking levels and total daily output, with Shuar juveniles and adolescents displaying significantly lower levels than adults (p < .05). Sex was not a significant predictor of cortisol levels (p > .05), as Shuar males and females displayed similar patterns of diurnal cortisol production across the life course. Moreover, age, sex, and BMI significantly interacted to moderate the rate of diurnal cortisol decline (p = .027). Overall, Shuar demonstrated relatively lower cortisol concentrations than high-income populations. CONCLUSIONS: This study expands the documented range of global variation in HPA axis activity and diurnal cortisol production and provides important insights into the plasticity of human stress physiology across diverse developmental and socioecological settings.

Guideline Review: European Association for the Study of Liver (EASL) Clinical Practice Guidelines on Haemochromatosis.

The European Association for the Study of the Liver (EASL) has recently (June 2022) produced new clinical practice guidelines for the investigation and management of haemochromatosis, to replace the previous document published in 2010. Here, we provide an overview of the principal changes recommended for the investigation and management of haemochromatosis arising from these guidelines and highlight particular areas where evidence is lacking and where future focus on specific research would improve patient treatment and outcomes. The guideline provides several important new recommendations that will have a meaningful impact on patient management. Specifically, the use of hepatic elastography as a non-invasive assessment of fibrosis, erythrocytapheresis as an alternative treatment modality to classical phlebotomy, surveillance for hepatocellular carcinoma, dietary recommendations in patients with haemochromatosis and guidance on controversial topics including the management of P.C282Y/p.H63D compound heterozygotes, which have been a source of controversy within the field. It is anticipated that the new guidance will affect the management of haemochromatosis patients commonly seen in gastroenterology, liver and related clinics (e.g. haematology and rheumatology) and with this publication we intend to highlight these changes so as to empower clinicians with the confidence to bring these improvements to their translational practice in the treatment of these patients.

The Analysis of Two Distinct Strategies toward the Enantioselective Formal Total Synthesis of (+)-Gelsenicine.

A full account of a formal enantioselective total synthesis of (+)-gelsenicine is described. Separate strategies based on catalytic cycloisomerization as the central step are considered. One plan involves chirality transfer from enantioenriched substrates, while the other employs asymmetric catalysis. The chirality transfer strategy is less effective, while in the latter, phosphoramidite- and bisphosphine-gold complexes are tested and ultimately provide a key intermediate in high enantiopurity in our Gelsemium alkaloid syntheses.

Serratus Anterior Plane Block for Clinically Suspected Rib Fractures in Prehospital and Retrieval Medicine.

Objective: To describe the use of the serratus anterior plane block (SAPB) in the prehospital and retrieval environment including the ability to accurately identify those patients with thoracic trauma and clinically suspected rib fractures who would benefit from this procedure.Methods: This is a retrospective case series of all patients with thoracic trauma and clinically suspected rib fractures who received SAPB by a prehospital and retrieval medical team in New South Wales, Australia, between 2018 and 2021. The primary outcome was to identify the proportion of patients who received appropriate blocks based on the criteria of reporting moderate pain after receiving adequate pre-block analgesia. Secondary outcomes included the proportions of patients with rib fractures identified on thoracic imaging, concomitant time-critical pathology, radiologist identification of fluid adjacent to the serratus anterior muscle, and local anesthetic systemic toxicity.Results: Of the 2004 patients who sustained thoracic trauma, only 13 received a SAPB. Nine (69.2%) met the predetermined definition of appropriate selection. Of the four patients who did not meet this criteria, three reported less than moderate pain and one did not receive adequate pre-block analgesia. There was no significant effect on median scene interval when compared to other thoracic trauma patients who did not receive a SAPB. Ten patients had rib fractures identified on in-patient imaging (chest x-ray or computed tomography (CT)) with a median (IQR) number of ribs fractured of 5 (interquartile range 2-10). Three of these patients had radiological flail segments. Prespecified time-critical pathology was identified in three patients (23.1%) on initial hospital imaging. Five out of eight patients with post-SAPB CT imaging (62.5%) available for radiologist review had fluid identified adjacent to the serratus anterior muscle. None of the 13 patients had local anesthetic systemic toxicity.Conclusion: The SAPB can be safely and successfully performed in the prehospital and retrieval environment, where clinicians can appropriately identify patients with thoracic trauma and clinically suspected rib fractures who would benefit from this technique. Further research is required to identify the ideal patient population to perform the SAPB upon and compare its performance to current analgesic options.

Chirality Transfer and Asymmetric Catalysis: Two Strategies toward the Enantioselective Formal Total Synthesis of (+)-Gelsenicine.

Two strategies are described en route to an enantioselective total synthesis of gelsenicine. One approach centers on a chirality transfer cycloisomerization that ultimately fell short. Separately, an asymmetric catalysis route utilizing bisphosphine-gold-catalyzed cycloisomerization was pursued. A catalytic system was identified that provided a synthetic intermediate in our Gelsemium alkaloid syntheses in high enantiopurity and with absolute configuration determined by electronic circular dichroism, thus representing an enantioselective formal total synthesis of (+)-gelsenicine.

Low prevalence of anemia among Shuar communities of Amazonian Ecuador.

OBJECTIVE: Anemia is an important global health challenge. We investigate anemia prevalence among Indigenous Shuar of Ecuador to expand our understanding of population-level variation, and to test hypotheses about how anemia variation is related to age, sex, and market integration. METHODS: Hemoglobin levels were measured in a total sample of 1650 Shuar participants (ages 6 months to 86 years) from 46 communities between 2008 and 2017 to compare anemia prevalence across regions characterized by different levels of market integration. RESULTS: Shuar anemia rates among children under 15 years (12.2%), adult women (10.5%), and adult men (5.3%) were less than half of those previously documented in other neo-tropical Indigenous populations. Anemia prevalence did not vary between more traditional and market integrated communities (OR = 0.47, p = .52). However, anemia was negatively associated with body mass index (OR = 0.47, p = .002). CONCLUSIONS: Compared to other South American Indigenous populations, anemia prevalence is relatively low among Shuar of Ecuador and invariant with market integration. Understanding this pattern can provide valuable insights into anemia prevention among at-risk populations.

Market integration and soil-transmitted helminth infection among the Shuar of Amazonian Ecuador.

BACKGROUND: Soil-transmitted helminth (STH) infections have many negative health outcomes (e.g., diarrhea, nutritional deficiencies) that can also exacerbate poverty. These infections are generally highest among low-income populations, many of which are also undergoing market integration (MI; increased participation in a market-based economy). Yet the direct impact of MI-related social and environmental changes on STH infection patterns is poorly understood, making it unclear which lifestyle factors should be targeted to better control disease spread. This cross-sectional study examines if household infrastructure associated with greater MI is associated with lower STH burdens among Indigenous Ecuadorian Shuar. METHODS: Kato-Katz fecal smears were used to determine STH infection status and intensity (n = 620 participants; 308 females, 312 males, aged 6 months-86 years); Ascaris lumbricoides (ascarid) and Trichuris trichiura (whipworm) were the primary infection types detected. Structured interviews assessing lifestyle patterns (e.g., measures of household infrastructure) measured participant MI. Multilevel regression analyses and zero-inflated negative binomial regression models tested associations between MI measures and STH infection status or intensity, controlling for individual and community characteristics. RESULTS: Participants residing in more market-integrated households exhibited lower infection rates and intensities than those in less market integrated households. Parasite infection status and T. trichiura infection intensity were lower among participants living in houses with wood floors than those with dirt floors, while individuals using well or piped water from a spring exhibited lower A. lumbricoides infection intensities compared to those using river or stream water. Unexpectedly, latrine type was not significantly related to STH infection status or intensity. These results suggest that sources of exposure differ between the two helminth species. CONCLUSIONS: This study documents associations between household measures and STH infection among an Indigenous population undergoing rapid MI. These findings can help healthcare programs better target interventions and reduce STH exposure among at-risk populations.

Quality improvement in paediatric radiation oncology through peer review.

INTRODUCTION: Around 300 children in Australia and New Zealand (ANZ) undergo a course of radiation treatment (RT) each year. A fortnightly videoconference for radiation oncologists managing children started in 2013. We conducted an audit of the videoconference to assess its influence on the care of children who receive RT in ANZ. METHODS: De-identified data from minutes (August 2013-December 2019) were analysed retrospectively using three categories: meeting participation, case presentations and management decisions. RESULTS: There were 119 meetings and 334 children discussed over the six-year audit period with regular attendance from four of 11 centres treating children in ANZ. Most cases (80%) were discussed prior to RT. A change in the overall management plan was recommended for around one in eight patients (35/334, 13%). RT plan reviews were performed in 79 cases (23%). Adjustments were made to the target volume contours or treatment plan in 8% (6/79). CONCLUSION: Increasing the frequency of the meeting to weekly and compliant with the RANZCR Peer Review Audit Tool has the capacity to review all paediatric RT patients in ANZ prior to RT and initiate changes for as many as one in eight children treated by RT each year. The meeting should be considered a core component necessary to maintain expertise in paediatric RT in all centres providing RT for children in ANZ while also acting as a proton referral panel as more children are referred abroad for proton therapy before the Australian Bragg Centre for Proton Therapy opens in Adelaide in 2024.

Soil-transmitted helminth infection and intestinal inflammation among the Shuar of Amazonian Ecuador.

OBJECTIVES: Little research exists documenting levels of intestinal inflammation among indigenous populations where exposure to macroparasites, like soil-transmitted helminths (STHs), is common. Reduced STH exposure is hypothesized to contribute to increased prevalence of elevated intestinal inflammation in wealthy nations, likely due to coevolutionary histories between STHs and human immune systems that favored anti-inflammatory pathways. Here, we document levels of intestinal inflammation and test associations with STH infection among the Shuar of Ecuador, an indigenous population undergoing socioeconomic/lifestyle changes that influence their hygienic environment. We predict that fecal calprotectin (FC; a measure of intestinal inflammation) will be lower in STH infected individuals and that FC will be negatively associated with infection intensity. METHODS: Stool samples to analyze FC levels and STH infection were collected from 69 Shuar participants (ages 5-75 years). Children (<15 years) and adults (15+ years) were analyzed separately to understand the role of exposure in immune system development and the intestinal inflammatory response. RESULTS: Two species of STH were present: Ascaris lumbricoides and Trichuris trichiura. The relationships between infection and intestinal inflammation were age- and species-specific. While no significant relationships were found among adults, children who were singly infected with T. trichiura had lower FC levels than uninfected children. Infection intensity was not significantly associated with FC in children or adults. CONCLUSIONS: These preliminary results provide limited support for our hypotheses, documenting tentative age- and species-specific associations between FC and infection status. Findings may point to the importance of species-specific STH exposure during immune system development.

Is the measurement of copper and iron in liver biopsies reliable? Results from a pilot external quality assurance scheme.

The determination of copper and iron in liver biopsies have important roles in the diagnosis of Wilson's Disease and haemochromatosis respectively. An external quality assurance scheme is essential for analytical validation of results, however, none was available for these analytes at the time of this investigation. Accordingly a pilot scheme was established. The results of this scheme and of a corresponding questionnaire are recorded. Twenty-nine identical sets of lyophilised certified reference materials or dried aliquots of livers purchased from local stores were distributed to 26 specialist trace element laboratories offering this clinical service. Using results returned, target values were assigned and analytical imprecision and accuracy were assessed. Laboratories were also asked to complete a questionnaire regarding details of sample preparation, analytical method and interpretation. Accuracy was worse than ± 50% at least one result in 38% of laboratories measuring copper and 57% measuring iron. Within-batch imprecisions poorer than ± 50% were found in 20% and 23% of liver copper and iron results respectively. Accuracy was found to be statistically poorer if sample weights less than 3 mg were measured. Reference ranges were frequently absent from reports or disagreed with international guidelines. A significant proportion of laboratories are unable to provide consistently reliable analytical performance to the extent that misdiagnosis may occur. The current diagnostic service is further compromised by the lack, or unreliability, of appropriate reference ranges provided on reports making interpretation more difficult. Without improvement, a review of current guidelines may be necessary.

Hypofractionated radiation treatment following mastectomy in early breast cancer: the Christchurch experience.

INTRODUCTION: Although hypofractionated radiotherapy (HFRT) has become an accepted option for whole-breast irradiation after breast-conserving surgery, there is limited evidence to support HFRT to the chest wall following mastectomy. We retrospectively analysed post-mastectomy patients treated with HFRT in Christchurch to determine whether HFRT yields acceptable efficacy and toxicity. METHODS: The Christchurch oncology database was used to identify breast cancer patients treated with adjuvant HFRT to the chest wall following a mastectomy between 2003 and 2008. Eligible post-mastectomy patients were treated with 40 Gy in 16 daily fractions. Treatment outcomes assessed included local recurrence-free survival, breast cancer survival, overall survival and acute toxicities. RESULTS: One hundred thirty-three patients were identified. The median follow-up period was 5.03 years. Three patients had a local recurrence as a first event, resulting in 5-year local recurrence-free survival of 97.6%. Five-year overall survival and 5-year breast cancer survival were 74.7% and 77.7%, respectively. The prospectively assessed acute toxicities were mostly grade 1. In particular, the incidence of grade 2 skin toxicity was 10.7%, and no patients experienced grade 3 skin toxicity. CONCLUSION: The high local control rate with HFRT, combined with acceptable toxicity and the practical benefits of a shorter treatment time, supports its ongoing use in the eligible patient group. A randomised controlled trial would be necessary to more completely assess the acute and long-term toxicity of HFRT compared with standard fractionation.

Analysis of organometal(loid) compounds in environmental and biological samples.

Measurement of the different physicochemical forms of metals and metalloids is a necessary pre-requisite for the detailed understanding of an element's interaction with environmental and biological systems. Such chemical speciation data is important in a range of areas, including toxicology, ecotoxicology, biogeochemistry, food safety and nutrition. This chapter considers developments in the speciation analysis of organometallic compounds (OMCs), focusing on those of As, Hg, Se and Sn. Typically, organometallic analysis requires a chromatographic separation prior to analyte detection and gas chromatography (GC), high performance liquid chromatography (HPLC) or capillary electrophoresis (CE) can serve this purpose. Following separation, detection is achieved using element specific detectors (ESDs) such as inductively coupled plasma mass spectrometry (ICP-MS), inductively coupled plasma optical emission spectroscopy (ICP-OES), atomic fluorescence spectrometry (AFS), atomic absorption spectrometry (AAS) or atmospheric pressure ionization mass spectrometry (API-MS). Techniques employing a vapor generation (VG) stage prior to detection are also discussed. Complementary structural and quantitative data may be acquired through the combination of elemental and molecular mass spectrometry. The advantages and disadvantages of the various analytical systems are discussed, together with issues related to quantification and quality management.

Bacterial degradation of arsenobetaine via dimethylarsinoylacetate.

Microorganisms from Mytilus edulis (marine mussel) degraded arsenobetaine, with the formation of trimethylarsine oxide, dimethylarsinate and methylarsonate. Four bacterial isolates from these mixed-cultures were shown by HPLC/hydride generation-atomic fluorescence spectroscopy (HPLC/HG-AFS) analysis to degrade arsenobetaine to dimethylarsinate in pure culture; there was no evidence of trimethylarsine oxide formation. Two of the isolates ( Paenibacillussp. strain 13943 and Pseudomonas sp. strain 13944) were shown by HPLC/inductively coupled plasma-mass spectrometry (HPLC/ICPMS) analysis to degrade arsenobetaine by initial cleavage of a methyl-arsenic bond to form dimethylarsinoylacetate, with subsequent cleavage of the carboxymethyl-arsenic bond to yield dimethylarsinate. Arsenobetaine biodegradation by pure cultures was biphasic, with dimethylarsinoylacetate accumulating in culture supernatants during the culture growth phase and its removal accompanying dimethylarsinate formation during a carbon-limited stationary phase. The Paenibacillus sp. also converted exogenously supplied dimethylarsinoylacetate to dimethylarsinate only under carbon-limited conditions. Lysed-cell extracts of the Paenibacillus sp. showed constitutive expression of enzyme(s) capable of arsenobetaine degradation through methyl-arsenic and carboxymethyl-arsenic bond cleavage. The work establishes the capability of particular bacteria to cleave both types of arsenic-carbon bonds of arsenobetaine and demonstrates that mixed-community functioning is not an obligate requirement for arsenobetaine biodegradation.