Search Results (20)

Background: In patients with curatively resected pancreatic adenocarcinoma who have undergone neoadjuvant chemotherapy (NACT), evidence supporting the benefit of additional adjuvant chemotherapy (ACT) remains limited. We aim to identify favorable factors contributing to survival benefits in resected pancreatic adenocarcinoma after NACT. Methods: This is a retrospective cohort study of pancreatic adenocarcinoma patients who underwent NACT followed by curative surgical resection between 2008 and 2023 at a single academic institution. Univariate and multivariable analyses were conducted to identify factors contributing to disease-free survival (DFS) and overall survival (OS). Results: A total of 230 patients with a median age of 68 years (IQR, 62–72 years) were included. All patients underwent curative surgical resection. Of these, 42% received neoadjuvant modified (m) FOLFIRINOX (96/230), 15% received gemcitabine plus nab-paclitaxel (GEM-NAB) (34/230), and 43% received gemcitabine, docetaxel, and capecitabine (GTX) (100/230). In univariate analysis, lower College of American Pathologists (CAP) tumor regression grade (TRG) (0–1 vs. 2–3, median DFS: 29.8 vs. 14.2 months, p = 0.0081) and receipt of ACT (Yes vs. No, median DFS: 22.2 vs. 12.4 months, p < 0.0001) demonstrated significant associations with superior DFS. Multivariable analysis identified receipt of ACT as an independent predictor of superior DFS (HR 0.55, 95% CI: 0.39–0.78, p = 0.0007) and OS (HR 0.49, 95% CI: 0.33–0.71, p = 0.0002). However, the NACT regimen (mFOLFIRINOX vs. GEM-NAB) and the transition between neoadjuvant and adjuvant therapy (de-escalation vs. continuation vs. change) did not correlate with DFS or OS. The duration of perioperative chemotherapy showed a trend toward improved survival outcomes, though not statistically significant (6 months vs. <6 months: DFS, 19.4 vs. 16.2 months, p = 0.1448; OS, 49.6 vs. 30.4 months, p = 0.0623). In the following subgroup analyses, receipt of ACT provided DFS/OS benefits in patients who did not achieve a major pathologic response, pN0, or R0 resection (DFS: p = 0.0003; OS: p < 0.0001). However, it did not provide DFS/OS benefits in those who achieved a major pathologic response with pN0/R0 to NACT (DFS: p = 0.8036; OS: p = 0.1877). Conclusions: In resected pancreatic adenocarcinoma following NACT, receiving ACT was associated with favorable survival outcomes. Additional ACT appears to benefit patients who did not achieve a major pathologic response (pN0 or R0) to neoadjuvant therapy, with limited benefit for those who achieved a major response with pN0/R0. The specific NACT regimen (mFOLFIRINOX vs. GEM-NAB) and changes in ACT from NACT did not significantly influence survival outcomes in our cohort. Full article

Background: Thoracolumbar transcutaneous spinal cord stimulation (tSCS) non-invasively evokes posterior root-muscle reflexes (PRMR) with the aim of neuromodulating sensorimotor function following spinal cord injury. Research is still in its infancy regarding the effect of body position on the nature of these spinally evoked responses. Therefore, the aim of this study was to investigate the influence of body position on the nature of PRMR responses during tSCS. Methods: A total of 11 (6M, 5F) participants completed a full PRMR recruitment curve from 10 ma up to 120 ma (10 ma increments) at the T11/12 intervertebral space using a singular 3.2 cm diameter cathode. At each intensity, three paired pulses (50 ms inter-pulse interval), followed by three singular pulses with a six-second delay were applied in each body position (supine, supine 90-90, sitting and standing) in a randomised order. The PRMR responses in lower limb muscles were recorded using wireless electromyographic sensors placed on the Soleus, Tibialis Anterior, Rectus Femoris and Bicep Femoris long head. A two-way (body position × muscle) repeated measures analysis of variance was used to investigate the effect of body position on PRMR-evoked responses. Results: There was a significant main effect of body position on PRMR resting motor threshold (RMT) (p < 0.001), first response peak-to-peak amplitude (p = 0.003) and percentage post-activation depression (%PAD) (p = 0.012). Sitting had significantly higher RMT and significantly lower first response peak-to-peak amplitudes compared to all other positions, but significant differences in %PAD were only detectible between supine and standing. Conclusions: Body position influences the nature of PRMR-evoked responses during tSCS. Full article

Introduction: The opioid overdose crisis in the United States has become a significant national emergency. Buprenorphine, a primary medication for individuals coping with opioid use disorder (OUD), presents promising pharmacokinetic properties for use in primary care settings, and is often delivered as a take-home therapy. The COVID-19 pandemic exacerbated the scarcity of access to buprenorphine, leading to dire consequences for those with OUD. Most existing studies, primarily focused on the immediate aftermath of the COVID-19 outbreak, highlight the challenges in accessing medications for opioid use disorder (MOUDs), particularly buprenorphine. However, these studies only cover a relatively short timeframe. Methods: To bridge this research gap, in our study, we utilized 33 months of California’s prescription drug monitoring program (PDMP) data to provide insights into real-world buprenorphine dispensing trends since the onset of the pandemic from 2018 to 2021, focusing on outcomes such as patient counts, prescription volumes, prescriber involvement, days’ supply, and dosage. Statistical analysis employed interrupted time series analysis to measure changes in trends before and during the pandemic. Results: We found no significant impact on patient counts or prescription volumes during the pandemic, although it impeded the upward trajectory of prescriber numbers that was evident prior to the onset of the pandemic. An immediate increase in days’ supply per prescription was observed post-pandemic. Conclusion: Our findings differ in comparison to previous data regarding the raw monthly count of patients and prescriptions. The analysis encompassed uninsured patients, offering a comprehensive perspective on buprenorphine prescribing in California. Our study’s insights contribute to understanding the impact of COVID-19 on buprenorphine access, emphasizing the need for policy adjustments. Full article

Concussion may affect sport performance capabilities related to the visual perception of environmental events, rapid decision-making, and the generation of effective movement responses. Immersive virtual reality (VR) offers a means to quantify, and potentially enhance, the speed, accuracy, and consistency of responses generated by integrated neural processes. A cohort of 24 NCAA Division I male wrestlers completed VR assessments before and after a 3-week VR training program designed to improve their perceptual-motor performance. Prior to training, the intra-individual variability (IIV) among 40 successive task trials for perceptual latency (i.e., time elapsed between visual stimulus presentation and the initiation of movement response) demonstrated strong discrimination between 10 wrestlers who self-reported a history of concussion from 14 wrestlers who denied ever having sustained a concussion (Area Under Curve ≥ 0.750 for neck, arm, and step movements). Natural log transformation improved the distribution normality of the IIV values for both perceptual latency and response time (i.e., time elapsed between visual stimulus presentation and the completion of movement response). The repeated measures ANOVA results demonstrated statistically significant (p < 0.05) pre- and post-training differences between groups for the IIV in perceptual latency and the IIV in response time for neck, arm, and step movements. Five of the six IIV metrics demonstrated a statistically significant magnitude of change for both groups, with large effect sizes. We conclude that a VR assessment can detect impairments in perceptual-motor performance among college wrestlers with a history of concussion. Although significant post-training group differences were evident, VR training can yield significant performance improvements in both groups. Full article

Transcutaneous spinal cord stimulation (tSCS) at the cervical level may facilitate improved upper-limb function in those with incomplete tetraplegia. While clinical trials are ongoing, there is still much debate regarding the transmission pathway as well as appropriate stimulation parameters. This study aimed to explore the extent to which cervical tSCS can induce mono-synaptic reflexes in discrete upper-limb motor pools and examine the effects of altering stimulus location and intensity. Methods: Fourteen participants with intact nervous systems completed two laboratory visits, during which posterior root-muscle reflexes (PRMRs) were evoked via a 3 × 3 cathode matrix applied over the cervical spine. An incremental recruitment curve at the C7 vertebral level was initially performed to attain resting motor threshold (RMT) in each muscle. Paired pulses (1 ms square monophasic with inter-pulse interval of 50 ms) were subsequently delivered at a frequency of 0.25 Hz at two intensities (RMT and RMT + 20%) across all nine cathode positions. Evoked responses to the 1st (PRMR₁) and 2nd (PRMR₂) stimuli were recorded in four upper-limb muscles. Results: A significant effect of the spinal level was observed in all muscles for PRMR₁, with greater responses being recorded caudally. Contralateral stimulation significantly increased PRMR₁ in Biceps Brachii (p < 0.05, F = 4.9, η2 = 0.29), Flexor Carpi Radialis (p < 0.05, F = 4.9, η2 = 0.28) and Abductor Pollicis Brevis (p < 0.01, F = 8.9, η2 = 0.89). Post-activation depression (PAD) was also significantly increased with contralateral stimulation in Biceps Brachii (p = 0.001, F = 9.3, η2 = 0.44), Triceps Brachii (p < 0.05, F = 5.4, η2 = 0.31) and Flexor Carpi Radialis (p < 0.001, F = 17.4, η2 = 0.59). Conclusions: A level of unilateral motor pool selectivity may be attained by altering stimulus intensity and location during cervical tSCS. Optimising these parameters may improve the efficacy of this neuromodulation method in clinical cohorts. Full article

Patients with high-grade serous ovarian cancer (HGSC) who have no visible residual disease (R0) after primary surgery have the best clinical outcomes, followed by patients who undergo neoadjuvant chemotherapy (NACT) and have a response enabling interval cytoreductive surgery. Clinically useful biomarkers for predicting these outcomes are still lacking. Extracellular vesicles (EVs) have been recognized as liquid biopsy-based biomarkers for early cancer detection and disease surveillance in other disease settings. In this study, we performed extensive molecular characterization of serum-derived EVs and correlated the findings with therapeutic outcomes in patients with HGSC. Using EV-DNA whole-genome sequencing and EV-RNA sequencing, we identified distinct somatic EV-DNA alterations in cancer-hallmark genes and in ovarian cancer genes, as well as significantly altered oncogenic pathways between the R0 group and NACT groups. We also found significantly altered EV-RNA transcriptomic variations and enriched pathways between the groups. Taken together, our data suggest that the molecular characteristics of EVs could enable prediction of patients with HGSC who could undergo R0 surgery or respond to chemotherapy. Full article

Chemotherapy remains a primary treatment for metastatic cancer, with tumor response being the benchmark outcome marker. However, therapeutic response in cancer is unpredictable due to heterogeneity in drug delivery from systemic circulation to solid tumors. In this proof-of-concept study, we evaluated chemotherapy concentration at the tumor-site and its association with therapy response by applying a mathematical model. By using pre-treatment imaging, clinical and biologic variables, and chemotherapy regimen to inform the model, we estimated tumor-site chemotherapy concentration in patients with colorectal cancer liver metastases, who received treatment prior to surgical hepatic resection with curative-intent. The differential response to therapy in resected specimens, measured with the gold-standard Tumor Regression Grade (TRG; from 1, complete response to 5, no response) was examined, relative to the model predicted systemic and tumor-site chemotherapy concentrations. We found that the average calculated plasma concentration of the cytotoxic drug was essentially equivalent across patients exhibiting different TRGs, while the estimated tumor-site chemotherapeutic concentration (eTSCC) showed a quadratic decline from TRG = 1 to TRG = 5 (p < 0.001). The eTSCC was significantly lower than the observed plasma concentration and dropped by a factor of ~5 between patients with complete response (TRG = 1) and those with no response (TRG = 5), while the plasma concentration remained stable across TRG groups. TRG variations were driven and predicted by differences in tumor perfusion and eTSCC. If confirmed in carefully planned prospective studies, these findings will form the basis of a paradigm shift in the care of patients with potentially curable colorectal cancer and liver metastases. Full article

The ocean provides resources key to human health and well-being, including food, oxygen, livelihoods, blue spaces, and medicines. The global threat to these resources posed by accelerating ocean acidification is becoming increasingly evident as the world’s oceans absorb carbon dioxide emissions. While ocean acidification was initially perceived as a threat only to the marine realm, here we argue that it is also an emerging human health issue. Specifically, we explore how ocean acidification affects the quantity and quality of resources key to human health and well-being in the context of: (1) malnutrition and poisoning, (2) respiratory issues, (3) mental health impacts, and (4) development of medical resources. We explore mitigation and adaptation management strategies that can be implemented to strengthen the capacity of acidifying oceans to continue providing human health benefits. Importantly, we emphasize that the cost of such actions will be dependent upon the socioeconomic context; specifically, costs will likely be greater for socioeconomically disadvantaged populations, exacerbating the current inequitable distribution of environmental and human health challenges. Given the scale of ocean acidification impacts on human health and well-being, recognizing and researching these complexities may allow the adaptation of management such that not only are the harms to human health reduced but the benefits enhanced. Full article

In the face of global human population increases, there is a need for efficacious integrated pest management strategies to improve agricultural production and increase sustainable food production. To counteract significant food loses in crop production, novel, safe and efficacious measures should be tested against bacterial pathogens. Pectobacteriaceae species are one of the causative agents of the bacterial rot of onions ultimately leading to crop losses due to ineffective control measures against these pathogens. Therefore, the aim of this study was to isolate and characterize bacteriophages which could be formulated in a cocktail and implemented in planta under natural environmental conditions. Transmission electron microscopy (TEM) and genome analysis revealed Siphoviridae and Podoviridae family bacteriophages. To test the protective effect of a formulated phage cocktail against soft rot disease, three years of field trials were performed, using three different methods of treatment application. This is the first study to show the application of a phage cocktail containing Podoviridae and Siphoviridae bacteriophages capable of protecting onions against soft rot in field conditions. Full article

This article explores how care homes—and, specifically, their common features such as dementia care units and locked doors and gates—impact on the human rights of people living with dementia. We suggest that congregation, separation and confinement of people living with dementia by the care home built environment constitute ‘segregation’. In the specific context of residential aged care facilities in Australia, we draw on the United Nations Convention on the Rights of Persons with Disabilities (‘CRPD’) to frame this segregation as an injustice. We focus on the rights to non-discrimination (Article 5), liberty and security of the person (Article 14), equality before the law (Article 12), accessibility (Article 9), and independent living and community inclusion (Article 19). Our analysis shows that addressing segregation must involve structural and resource reforms that are transformative in bringing about new ways of living and relating to each other. Such reforms are directed towards providing meaningful alternatives and appropriate supports to make choices from a range of alternative residency and support options, and building communities that are free from ableism, ageism and other systems of oppression that contribute to confinement and segregation. Full article

Housing conditions have been an enduring focus for public health activity throughout the modern public health era. However, the nature of the housing and health challenge has changed in response to an evolution in the understanding of the diverse factors influencing public health. Today, the traditional public health emphasis on the type and quality of housing merges with other wider determinants of health. These include the neighbourhood, community, and “place” where a house is located, but also the policies which make access to a healthy house possible and affordable for everyone. Encouragingly, these approaches to policy and action on housing have the potential to contribute to the “triple win” of health and well-being, equity, and environmental sustainability. However, more effective housing policies (and in public health in general) that adopt more systemic approaches to addressing the complex interactions between health, housing, and wider environment are needed. This paper illustrates some of the key components of the housing and health challenge in developed countries, and presents a conceptual model to co-ordinate activities that can deliver the “triple win.” This is achieved by offering a perspective on how to navigate more effectively, inclusively and across sectors when identifying sustainable housing interventions. Full article

Kiwifruit are a nutrient dense food and an excellent source of vitamin C. Supplementation of the diet with kiwifruit enhances plasma vitamin C status and epidemiological studies have shown an association between vitamin C status and reduced insulin resistance and improved blood glucose control. In vitro experiments suggest that eating kiwifruit might induce changes to microbiota composition and function; however, human studies to confirm these findings are lacking. The aim of this study was to investigate the effect of consuming two SunGold kiwifruit per day over 12 weeks on vitamin C status, clinical and anthropometric measures and faecal microbiota composition in people with prediabetes. This pilot intervention trial compared baseline measurements with those following the intervention. Participants completed a physical activity questionnaire and a three-day estimated food diary at baseline and on completion of the trial. Venous blood samples were collected at each study visit (baseline, 6, 12 weeks) for determination of glycaemic indices, plasma vitamin C concentrations, hormones, lipid profiles and high-sensitivity C-reactive protein. Participants provided a faecal sample at each study visit. DNA was extracted from the faecal samples and a region of the 16S ribosomal RNA gene was amplified and sequenced to determine faecal microbiota composition. When week 12 measures were compared to baseline, results showed a significant increase in plasma vitamin C (14 µmol/L, p < 0.001). There was a significant reduction in both diastolic (4 mmHg, p = 0.029) and systolic (6 mmHg, p = 0.003) blood pressure and a significant reduction in waist circumference (3.1 cm, p = 0.001) and waist-to-hip ratio (0.01, p = 0.032). Results also showed a decrease in HbA1c (1 mmol/mol, p = 0.005) and an increase in fasting glucose (0.1 mmol/L, p = 0.046), however, these changes were small and were not clinically significant. Analysis of faecal microbiota composition showed an increase in the relative abundance of as yet uncultivated and therefore uncharacterised members of the bacterial family Coriobacteriaceae. Novel bacteriological investigations of Coriobacteriaceae are required to explain their functional relationship to kiwifruit polysaccharides and polyphenols. Full article

The influence of early life exposures on later life disease has for some time provided clues to modifiable risk factors of disease. The “atopic march” is thought to play a role in the progression of allergic diseases and may offer an opportunity to lower asthma’s health and socioeconomic burden, although evidence remains controversial. We aimed to examine the relationship between early life eczema and asthma later in life. Using the National Child Development Study, we examined infant eczema and childhood and adult asthma. Data related to asthma or wheezing bronchitis were available for 13,503 (73%; 95% CI 72–74), 11,503 (61%; 95% CI 60–61), 12,524 (68%; 95% CI 67–69), 11,194 (60%; 95% CI 60–60), 9377 (51%; 95% CI 51–51), and 9760 (53%; 95% CI 52–53) subjects at ages 11, 16, 23, 33, 44, and 50 years, respectively. Logistic regression models were fitted to examine each wave separately before and after adjusting for a range of potential confounders. Generalised estimating equation (GEE) methods were undertaken to examine the associations after pooling all data from questionnaires. The prevalence of self-reported asthma in those that had previously reported infant eczema ranged from 1.0%; 95% CI 0.9–1.4 (age 44 years) to 2.2%; 95% CI 2.1–2.3 (age 33 years). Participants with infant eczema had a 2–3-fold increased risk of reporting asthma in childhood and adulthood; this was 1.6 times at age 44 years when using spirometry measures. Similar effect sizes were observed in the GEE models when considering all participants (OR 2.9; 95% CI 2.6–3.2). Childhood and adult asthma were consistently associated with infant eczema both by using the self-reported data and lung measures. Full article

Spruce budworm, Choristoneura fumiferana (Clem.), defoliation has been shown to affect the occurrence of crown fire in Ontario, highlighting the need to better understand the driving factors of this effect on forest structure, including changes in fuel loading, type and position. Here, we investigate five boreal mixedwood sites within four zones that experienced different durations of continuous defoliation by spruce budworm in northeastern Ontario. Duration of defoliation had significant effects on vertical stand components, namely, host overstory to host understory crown overlap, host overstory and host understory crown to downed woody debris overlap, and downed woody debris height and quantity. Vertical stand components tended to increase with the duration of continuous defoliation, with the highest vertical fuel continuity occurring after 16 years of continuous defoliation. Such increases in the vertical spatial continuity of fuels may be a key reason for the greater percentage of area burned in those forests which have recently sustained a spruce budworm outbreak. Full article

Wildfires and outbreaks of the spruce budworm, Choristoneura fumiferana (Clem.), are the two dominant natural disturbances in Canada’s boreal forest. While both disturbances have specific impacts on forest ecosystems, it is increasingly recognized that their interactions also have the potential for non-linear behavior and long-lasting legacies on forest ecosystems’ structures and functions. Previously, we showed that, in central Canada, fires occurred with a disproportionately higher frequency during a ‘window of opportunity’ following spruce budworm defoliation. In this study, we use Ontario’s spatial databases for large fires and spruce budworm defoliation to locate where these two disturbances likely interacted. Classification tree and Random Forest procedures were then applied to find how spruce budworm defoliation history, climate, and forest conditions best predict the location of such budworm–fire interactions. Results indicate that such interactions likely occurred in areas geographically bound by hardwood content in the south, the prevalence of the three major spruce budworm host species (balsam fir, white spruce and black spruce) in the north, and climate moisture in the west. The occurrence of a spruce budworm–fire interaction inside these boundaries is related to the frequency of spruce budworm defoliation. These patterns provide a means of distinguishing regions where spruce budworm attacks are likely to increase fire risk. Full article