Intensive Exposure Research Articles

Brain Magnetic Resonance Imaging Responses to Nonhypoxic Hypobaric Decompression

INTRODUCTION: The pathophysiological basis of neurological decompression sickness and the association between cerebral subcortical white matter (WM) change and nonhypoxic hypobaria remain poorly understood. Recent study of altitude decompression sickness risk evaluated acute WM responses to intensive hypobaric exposure using brain magnetic resonance imaging. METHODS: Six healthy men (20 to 50 yr) completed 6 h of hyperoxic hypobaria during three same-day altitude chamber decompressions to pressure altitudes ≥ 22,000 ft (6706 m). Research magnetic resonance imaging sequences, conducted on the days preceding and following decompression, evaluated subcortical WM integrity, cerebral blood flow, neuronal integrity (fractional anisotropy), and neurometabolite concentrations. RESULTS: No subcortical lesions were evident on diffusion weighted imaging and WM fractional anisotropy was unaffected. Mean WM blood flow was upregulated by 20% to over 25 mL · 100 g−1 · min−1. Gray matter flow was unchanged. There were no changes in gray matter or cerebellar neurometabolites. In parietal subcortical WM, levels of γ-aminobutyric acid (GABA) fell from (mean ± SD) 1.68 ± 0.2 to 1.35 ± 0.3 institutional units while glutathione (GSH) fell from 1.71 ± 0.4 to 1.25 ± 0.3 institutional units. Lactate increased postexposure in five subjects. CONCLUSIONS: Postexposure decrements in GABA and GSH imply WM insult with loss of neuroprotection and oxidative stress. An association between decrements in GABA and GSH support a common origin, while GSH decrements also correlate with WM blood flow responses. WM lactate increments are prone to error but suggest dysregulation of subcortical microvascular flow. WM neurometabolite and blood flow indices did not normalize by 24 h postexposure. Connolly D, Davagnanam I, Wylezinska-Arridge M, Mallon D, Wastling S, Lee VM. Brain magnetic resonance imaging responses to nonhypoxic hypobaric decompression. Aerosp Med Hum Perform. 2024; 95(10):733–740.

Chronic and Periodic Effects of Smoke from Crop Residue Combustion on Soil Enzymatic Activity

Wildfires lead to the emission of large volumes of toxic smoke, which is transported hundreds of kilometres away from the fires and can have a negative impact on soil, biota and humans. A series of modelling experiments on pyrogenic fumigation of soil were carried out to assess the effects of gaseous products from wildfires on soil biochemical parameters. The effects of chronic exposure to gaseous substances and periodic, repetitive effects of smoke exposure on soil were determined. The results were compared with a single intensive smoke exposure. It was found that pyrogenic impact significantly affected the change of enzymatic activity of ordinary chernozem. The degree of influence depended on the duration and periodicity of smoke exposure. In all experiments enzymes of oxidoreductase class (catalase, peroxidase, polyphenol oxidase) were more sensitive to fumigation than invertase from hydrolase class. The reason of suppression of enzymatic activity of soils is high concentrations of toxic gases. The following concentrations exceeded the maximum permissible concentrations for atmospheric air: CO 714 times, phenol (hydroxybenzene) 441 times, acetaldehyde 24100 times, formaldehyde 190 times. Accumulation of polycyclic aromatic hydrocarbons (PAHs) in soil after fumigation was revealed, the total content of PAHs was 377 ng/g. The highest values were recorded for naphthalene, where the concentration was 4.4 times higher than the maximum permissible and phenanthrene 2.8 times higher than the maximum permissible. It was found that 60-minute intensive smoke affects the soil to a lesser extent than chronic and periodic. Indicators of enzymatic activity of chernozem after such fumigation decreased by 15-33% depending on the enzyme, in chronic and periodic by 41-84 and 31-78%, respectively. The obtained data indicate a significant effect of smoke on enzymatic activity of soils under chronic and periodic exposure to gaseous products of combustion.

Anxiety matters: a pilot lab study into food, weight, and virtual body exposure in anorexia nervosa

BackgroundAnxiety is a core characteristic of anorexia nervosa and a potential target of exposure therapy, which requires a profound understanding of the patients’ fears in order to be successful. The knowledge about fears in anorexia nervosa that should be targeted during exposure therapy can be enriched by laboratory research to the precise emotional and behavioral responses of anorexia nervosa patients when they are exposed to disorder relevant fear stimuli.MethodsIn the laboratory, patients with anorexia nervosa (n = 15) and healthy controls (n = 51) were exposed to 1. their own body weight and a 10% higher body weight on the scale, 2. a standardized lab breakfast, and 3. five virtual bodies with different BMIs ranging from extreme underweight to lower healthy weight. The participants emotional (anxiety, disgust, satisfaction, acceptance) and behavioral responses (calorie consumption) were assessed. Patients with anorexia nervosa but not the healthy controls then received an intensive exposure treatment (~ 30 individual exposure sessions) targeting their individual fears, next to standard care. After the exposure treatment, it was investigated whether the patients’ responses to the laboratory tasks changed.ResultsAcross all tasks, the patients reported more anxiety than healthy controls. The patients also consumed less calories during the breakfast and accepted the different body weights on the scale less than healthy controls. During the virtual body exposure, the patients’ emotional responses did not differ per avatar but they reacted more negatively towards avatars with healthier weights than did healthy controls. After the exposure treatment, the patients reported less fears and they consumed more calories while their BMIs had increased. They were also more accepting of healthier weights.ConclusionsExposure to food-, body- and weight-related stimuli in the laboratory induces emotional reactions in patients with anorexia nervosa that are informative for the identification of exposure therapy treatment targets. In addition, exposure therapy targeting individual fears in patients with anorexia nervosa led to symptom reduction and is a promising intervention for the treatment of anorectic fears, though more research is needed to optimize its efficacy.

TRICHINELLA AND AT LEAST THREE SPECIES OF SARCOCYSTIS PARASITIZE THE MUSCLES OF BOBCATS (LYNX RUFUS) FROM MISSISSIPPI.

Muscles of 25 bobcats (Lynx rufus) from remote areas of Mississippi in 2017 were tested for parasites. Testing for Sarcocystis infections included microscopic examination of fresh unstained muscle squashes, pepsin digestion of hearts and tongues, and histological sections of paraffin-embedded tissues. Sarcocystis spp. infections were detected in the muscles of 21 (84%) by a combination of methods. Sarcocysts were detected in the unstained tongue squashes of 2 bobcats. Sarcocystis sp. bradyzoites were detected in the pepsin digests of 3 of 19 hearts, and 12 of 19 tongues. In paraffin-embedded histological sections, sarcocysts were detected in 7 of 25 hearts, 17 of 25 tongues, and 5 of 23 limb muscles. Based on the character of the cyst wall, at least 3 morphologic types of sarcocysts were detected: those with small spikes on the cyst wall, corresponding to Sarcocystis felis, those with long villar protrusions, corresponding to Sarcocystis neurona, and those lacking visible cyst wall protrusions, representing an unidentified type of sarcocyst. Myositis associated with sarcocysts was seen in the tongues of 3, and in the limb muscles of 1 bobcat. Multilocus genotyping of the DNA extracted from paraffin-embedded sections from 2 bobcats, employing 18S, 28S, COI, ITS-1, and 5.8S and rpoB genes, diagnosed Sarcocystis caninum, S. felis, Sarcocystis lutrae, and S. neurona. An encapsulated species of Trichinella was identified in the tongue of 1; it represents the first documented occurrences in bobcats from Mississippi. Taken together, these observations suggest intensive exposure of these wild carnivores to Trichinella tissue cysts, implies predation or scavenging on these tissues promotes parasite transmission, and raises caution concerning zoonotic risk when such meat is rendered for human consumption.

Post-treatment alterations in white matter integrity in PTSD: Effects on symptoms and functional connectivity a secondary analysis of an RCT

Post-traumatic stress disorder (PTSD) has been linked to altered communication within the limbic system, including reduced structural connectivity in the uncinate fasciculus (UNC; i.e., decreased fractional anisotropy; FA) and reduced resting-state functional connectivity (RSFC) between the hippocampus and ventromedial prefrontal cortex (vmPFC). Previous research has demonstrated attenuation of PTSD symptoms and alterations in RSFC following exposure-based psychotherapy. However, the relationship between changes in structural and functional connectivity patterns and PTSD symptoms following treatment remains unclear. To investigate this, we conducted a secondary analysis of data from a randomized clinical trial of intensive exposure therapy, evaluating alterations in UNC FA, hippocampus-vmPFC RSFC, and PTSD symptoms before (pre-treatment), 7 days after (post-treatment), and 30 days after (follow-up) the completion of therapy. Our results showed that post-treatment changes in RSFC were positively correlated with post-treatment and follow-up changes in UNC FA and that post-treatment changes in UNC FA were positively correlated with post-treatment and follow-up changes in PTSD symptoms. These findings suggest that early changes in functional connectivity are associated with sustained changes in anatomical connectivity, which in turn are linked to reduced PTSD symptom severity.

Beyond age and intensive exposure: Initial proficiency effects on adolescents’ second language proficiency in an international school

This study investigates the effects of biological age and intensive exposure on L2 learning in an International School context as regards variability in learning rate and L2 development among pre- versus mid-adolescent learners. Longitudinal data collection at three time-points over one year involved semi-guided interviews and written productions among 28 L1-French learners of English in two age groups, either 11 years or 15 years of age. The data were investigated using quantitative measures of accuracy, fluency and holistic proficiency, and analysed with robust repeated measures ANOVAs and ANCOVAs. The findings suggest that the one-year intensive experience of English learning in the International School promoted significant gains in accuracy and holistic proficiency, but only one aspect of fluency, i.e., speech rate. When initial proficiency as Time 1 performance was controlled, the 15-year-old learners performed better than their younger peers only in written proficiency, while the 11-year-olds showed a faster learning rate in some aspects of oral accuracy and fluency. However, initial proficiency eclipsed age and exposure effects on L2 proficiency development during the one-year intensive experience. These results suggest that, for the introduction of short intensive programs in instructed contexts, learners’ initial proficiency and biological age should be considered.

Ta'zîzu Dâfi'iyyati Thullâbi Riyâdh al-Athfâl li Tathwîri Mahârât al-Lughah al-'Arabiyyah al-Syafawiyyah min Khilâli Barâmiji al-Ta'lîm al-Mukatstsaf

This research study was motivated by several key factors. Firstly, the Arabic language holds great religious and cultural significance in Indonesia, as it is a core component of Islamic identity and practice, particularly in the context of Quranic education for children. However, many students at Quranic preschools struggle with developing proficiency in spoken Arabic. Additionally, educational literature emphasizes the critical role of student motivation in facilitating effective language learning outcomes. Therefore, it was important to investigate the factors influencing students' motivation to learn Arabic in this specific educational setting. Moreover, most prior research in this field has been conducted in non-Indonesian contexts, necessitating localized studies to explore the nuances of the Indonesian educational dynamics. Ultimately, this research aimed to help address the gaps in the existing body of knowledge around Arabic language instruction in Indonesian Quranic preschools. The researcher employed a quantitative approach and simple linear regression to analyze data collected from interviews, observations and questionnaires. Statistical tests of validity, reliability, normality, linearity and correlation were performed on the questionnaire data using SPSS. The iresults ishowed ithat iintensive Arabic classes had a significant effect on students' motivation to learn speaking skills, as idemonstrated iby ia ip-value iof iless ithan i0.05. Regression analysis further reported that these classes influenced motivation by 33.1%, as indicated by the R-squared value. Therefore, the intensive language exposure appeared to positively impact the kindergarteners' drive to develop their Arabic communication abilities.

LAYAR KECIL, MASALAH BESAR: ANALISIS PENGGUNAAN SMARTPHONE DAN PENGARUHNYA TERHADAP KETERLAMBATAN BERBICARA ANAK

This research aims to analyze the relationship between smartphone use and speech delay in children. Over the past decade, the penetration of smartphones has increased significantly, resulting in early and intensive screen exposure among children. This study employs a quantitative method with structured surveys and direct observation of 10 children aged 4-5 years from diverse socioeconomic backgrounds. Data was collected regarding the daily duration of smartphone use, the type of content accessed, and parent-child interactions while using the device. Preliminary results indicate a significant negative correlation between the duration of smartphone use and the development of speech abilities. Children who spend more time with smartphones tend to show delays in reaching language development milestones compared to those with less exposure. Furthermore, this study identifies that the quality of parent-child interaction during smartphone use, such as joint discussions and verbal interactions, can mitigate and minimize the negative impact of smartphone usage. This research provides vital insights into the impact of digital technology on child development and offers recommendations for parents and early childhood education practitioners. Keywords: smartphone use, speech delay, child development, digital technology, parent-child interaction.

The Influence of Mother Tongue Thinking on Second Language Writing

In the process of foreign language understanding, learning and using, thinking in the mother tongue will inevitably lead to the intervention of strong mother tongue contextual knowledge in the brain, and then activate the mother tongue expressions that match the mother tongue contextual knowledge. The object of second language acquisition is influenced by age, the current study set out to examine to what degree of acquisition (AOA), defined as a learner's first intensive exposure to a second language (L2) environment, mediates the final state of poster, spoken vocal accommodation. The more the students use mother tongue thinking in English writing, the shorter the writing text. This negative correlation is most prominent in the text-generation activities of writing. In fact, similar experimental findings were found in early studies. For intermediate learners, the longer the code-switching takes place in second-language writing, the shorter the text will be. Therefore, the research topic of this paper is the influence of mother tongue thinking transfer on second-language writing.

Effects of Aerobic Exercise on Brain Age and Health in Middle-Aged and Older Adults: A Single-Arm Pilot Clinical Trial.

Sleep disturbances are prevalent among elderly individuals. While polysomnography (PSG) serves as the gold standard for sleep monitoring, its extensive setup and data analysis procedures impose significant costs and time constraints, thereby restricting the long-term application within the general public. Our laboratory introduced an innovative biomarker, utilizing artificial intelligence algorithms applied to PSG data to estimate brain age (BA), a metric validated in cohorts with cognitive impairments. Nevertheless, the potential of exercise, which has been a recognized means of enhancing sleep quality in middle-aged and older adults to reduce BA, remains undetermined. We conducted an exploratory study to evaluate whether 12 weeks of moderate-intensity exercise can improve cognitive function, sleep quality, and the brain age index (BAI), a biomarker computed from overnight sleep electroencephalogram (EEG), in physically inactive middle-aged and older adults. Home wearable devices were used to monitor heart rate and overnight sleep EEG over this period. The NIH Toolbox Cognition Battery, in-lab overnight polysomnography, cardiopulmonary exercise testing, and a multiplex cytokines assay were employed to compare pre- and post-exercise brain health, exercise capacity, and plasma proteins. In total, 26 participants completed the initial assessment and exercise program, and 24 completed all procedures. Data are presented as mean [lower 95% CI of mean, upper 95% CI of mean]. Participants significantly increased maximal oxygen consumption (Pre: 21.11 [18.98, 23.23], Post 22.39 [20.09, 24.68], mL/kg/min; effect size: -0.33) and decreased resting heart rate (Pre: 66.66 [63.62, 67.38], Post: 65.13 [64.25, 66.93], bpm; effect size: -0.02) and sleeping heart rate (Pre: 64.55 [61.87, 667.23], Post: 62.93 [60.78, 65.09], bpm; effect size: -0.15). Total cognitive performance (Pre: 111.1 [107.6, 114.6], Post: 115.2 [111.9, 118.5]; effect size: 0.49) was significantly improved. No significant differences were seen in BAI or measures of sleep macro- and micro-architecture. Plasma IL-4 (Pre: 0.24 [0.18, 0.3], Post: 0.33 [0.24, 0.42], pg/mL; effect size: 0.49) was elevated, while IL-8 (Pre: 5.5 [4.45, 6.55], Post: 4.3 [3.66, 5], pg/mL; effect size: -0.57) was reduced. Cognitive function was improved by a 12-week moderate-intensity exercise program in physically inactive middle-aged and older adults, as were aerobic fitness (VO2max) and plasma cytokine profiles. However, we found no measurable effects on sleep architecture or BAI. It remains to be seen whether a study with a larger sample size and more intensive or more prolonged exercise exposure can demonstrate a beneficial effect on sleep quality and brain age.

The effect of incidental ethanol exposures on the formation of blood phosphatidylethanol.

Blood phosphatidylethanol (PEth), a metabolite of ethanol, is emerging as a direct biomarker of choice for characterizing ethanol consumption in clinical, research, and forensic contexts. An accumulating body of evidence, and a recent international consensus conference, supports a cutoff of 20 μg/L of PEth (16:0/18:1) to distinguish abstinence from beverage ethanol consumption. There is a dearth of research, however, on whether exposures to nonbeverage ethanol sources are sufficient to produce PEth concentrations that exceed this cutoff. To explore this possibility, we recruited 30 participants, who indicated past-90-day abstinence from beverage alcohol, to characterize their past-30-day nonbeverage ethanol exposures (including source, frequency, and intensity of exposures) and to undergo PEth testing. Two of the 30 participants (6.7%) produced PEth concentrations ≥20 μg/L. One of these participants (PEth = 26 μg/L) reported multiple ethanol exposure sources, including near-daily intensive exposures to ethanol vapor. The other participant (PEth = 49 μg/L) reported only once-daily use of an ethanol-containing mouthwash; the veracity of his abstinence claim is refuted. The results of this study support a rebuttable presumption that PEth ≥20 μg/L is indicative of beverage ethanol consumption. They suggest, however, that intensive, incidental alcohol exposures have the potential, under unusual circumstances, to result in PEth concentrations that modestly exceed this threshold.

Multifaceted, Brief Intensive Home-Based Exposure Treatment in Patients with Obsessive-Compulsive Disorder Who are Nonresponsive to Regular Cognitive Behavior Therapy: An Uncontrolled Pilot Study.

To test a multifaceted treatment program for patients with obsessive-compulsive disorder (OCD) who did not respond to regular cognitive behavior therapy (CBT). The treatment addresses several factors that may play a role in maintaining OCD. We designed a treatment consisting of a 6-day intensive, individual exposure in vivo with response prevention (ERP) format, with 24 therapist-assisted treatment hours at the patient's home and 12 self-controlled ERP hours, including behavioral activation and family interventions. Next, we investigated the effect (obsessive-compulsive symptoms, comorbidity, functioning, quality of life, OCD-related interaction patterns) and feasibility (dropout, treatment satisfaction, and organization) of this program using pre-post-tests, pre-follow-up tests, and qualitative data from patients, family members, and therapists. In a sample of 22 participants, obsessive-compulsive symptoms (Y-BOCS pre: 28.7, post: 15.9; Wilcoxon S-R tests P<0.01) improved significantly, as did most other effect measures. Results were largely, but not completely, preserved at 3-month follow-up. There was only 1 dropout. Patients, family members, and therapists were satisfied with the treatment. Implementation of the treatment did not pose difficulties. In nonresponders with OCD, a multifaceted, brief, intensive home-based ERP program targeting factors maintaining OCD is promising and feasible. Extra care is needed to maintain improvement.

Stepped Palliative Care for Patients With Advanced Lung Cancer

Despite the evidence for early palliative care improving outcomes, it has not been widely implemented in part due to palliative care workforce limitations. To evaluate a stepped-care model to deliver less resource-intensive and more patient-centered palliative care for patients with advanced cancer. Randomized, nonblinded, noninferiority trial of stepped vs early palliative care conducted between February 12, 2018, and December 15, 2022, at 3 academic medical centers in Boston, Massachusetts, Philadelphia, Pennsylvania, and Durham, North Carolina, among 507 patients who had been diagnosed with advanced lung cancer within the past 12 weeks. Step 1 of the intervention was an initial palliative care visit within 4 weeks of enrollment and subsequent visits only at the time of a change in cancer treatment or after a hospitalization. During step 1, patients completed a measure of quality of life (QOL; Functional Assessment of Cancer Therapy-Lung [FACT-L]; range, 0-136, with higher scores indicating better QOL) every 6 weeks, and those with a 10-point or greater decrease from baseline were stepped up to meet with the palliative care clinician every 4 weeks (intervention step 2). Patients assigned to early palliative care had palliative care visits every 4 weeks after enrollment. Noninferiority (margin = -4.5) of the effect of stepped vs early palliative care on patient-reported QOL on the FACT-L at week 24. The sample (n = 507) mostly included patients with advanced non-small cell lung cancer (78.3%; mean age, 66.5 years; 51.4% female; 84.6% White). The mean number of palliative care visits by week 24 was 2.4 for stepped palliative care and 4.7 for early palliative care (adjusted mean difference, -2.3; P < .001). FACT-L scores at week 24 for the stepped palliative care group were noninferior to scores among those receiving early palliative care (adjusted FACT-L mean score, 100.6 vs 97.8, respectively; difference, 2.9; lower 1-sided 95% confidence limit, -0.1; P < .001 for noninferiority). Although the rate of end-of-life care communication was also noninferior between groups, noninferiority was not demonstrated for days in hospice (adjusted mean, 19.5 with stepped palliative care vs 34.6 with early palliative care; P = .91). A stepped-care model, with palliative care visits occurring only at key points in patients' cancer trajectories and using a decrement in QOL to trigger more intensive palliative care exposure, resulted in fewer palliative care visits without diminishing the benefits for patients' QOL. While stepped palliative care was associated with fewer days in hospice, it is a more scalable way to deliver early palliative care to enhance patient-reported outcomes. ClinicalTrials.gov Identifier: NCT03337399.

Вредные вещества в воздухе рабочей зоны горнодобывающего сектора металлурги-ческой промышленности как факторы риска для здоровья работников (аналитический обзор)

Working conditions at non-ferrous metallurgical enterprises typically involve exposure to a whole set of harmful chemicals present in occupational air. These chemicals contribute to the development of pathologies in workers, respiratory diseases in particular. Research literature was analyzed using bibliographic databases in order to summarize available information on effects produced by harmful chemicals in workplace air on health of workers employed at mining enterprises. Respiratory diseases such as pneumoconiosis, acute and chronic dust bronchitis prevail among occupational pathologies typical for underground miners. Acute and chronic bronchitis prevail among respiratory diseases as health disorders resulting in temporary disability of miners dealing with non-ferrous metal mining. Huge amounts of dust appear in occupational air at mining enterprises due to drilling, blasting and ore crushing. Priority chemicals found in workplace air in mining industry include several carcinogens such as nickel, lead, formaldehyde, cadmium, and benzo(a)pyrene. There is a unidirectional effect produced by sulfur dioxide, nickel, nitrogen oxides, acrolein, formaldehyde, cadmium, and particular matter on the respiratory organs. The nervous system can be affected by manganese, lead, and selenium; the blood, by nickel, lead, and carbon oxide; the cardiovascular system, by carbon oxide and selenium. Working conditions of underground miners in non-ferrous metallurgy involve intensive exposure to chemicals in occupational air, which create health risks of occupational respiratory diseases and malignant tumors. Diseases of the nervous, immune, cardiovascular systems and the blood are also possible. When planning a set of preventive activities, it is advisable to identify groups of work-related diseases caused, among other things, by a specific chemical factor.

Harmful chemicals in occupational air in the ore mining sector of the metal industry as occupational health risk factors (Analytical review)

Working conditions at non-ferrous metallurgical enterprises typically involve exposure to a whole set of harmful chemicals present in occupational air. These chemicals contribute to the development of pathologies in workers, respiratory diseases in particular. Research literature was analyzed using bibliographic databases in order to summarize available information on effects produced by harmful chemicals in workplace air on health of workers employed at mining enterprises. Respiratory diseases such as pneumoconiosis, acute and chronic dust bronchitis prevail among occupational pathologies typical for underground miners. Acute and chronic bronchitis prevail among respiratory diseases as health disorders resulting in temporary disability of miners dealing with non-ferrous metal mining. Huge amounts of dust appear in occupational air at mining enterprises due to drilling, blasting and ore crushing. Priority chemicals found in workplace air in mining industry include several carcinogens such as nickel, lead, formaldehyde, cadmium, and benzo(a)pyrene. There is a unidirectional effect produced by sulfur dioxide, nickel, nitrogen oxides, acrolein, formaldehyde, cadmium, and particular matter on the respiratory organs. The nervous system can be affected by manganese, lead, and selenium; the blood, by nickel, lead, and carbon oxide; the cardiovascular system, by carbon oxide and selenium. Working conditions of underground miners in non-ferrous metallurgy involve intensive exposure to chemicals in occupational air, which create health risks of occupational respiratory diseases and malignant tumors. Diseases of the nervous, immune, cardiovascular systems and the blood are also possible. When planning a set of preventive activities, it is advisable to identify groups of work-related diseases caused, among other things, by a specific chemical factor.

Precision immuno-oncology approach for four malignant tumors in siblings with constitutional mismatch repair deficiency syndrome

Constitutional mismatch repair deficiency (CMMRD) is a rare syndrome characterized by an increased incidence of cancer. It is caused by biallelic germline mutations in one of the four mismatch repair genes (MMR) genes: MLH1, MSH2, MSH6, or PMS2. Accurate diagnosis accompanied by a proper molecular genetic examination plays a crucial role in cancer management and also has implications for other family members. In this report, we share the impact of the diagnosis and challenges during the clinical management of two brothers with CMMRD from a non-consanguineous family harbouring compound heterozygous variants in the PMS2 gene. Both brothers presented with different phenotypic manifestations and cancer spectrum. Treatment involving immune checkpoint inhibitors significantly contributed to prolonged survival in both patients affected by lethal gliomas. The uniform hypermutation also allowed immune-directed treatment using nivolumab for the B-cell lymphoma, thereby limiting the intensive chemotherapy exposure in this young patient who remains at risk for subsequent malignancies.

Use of an Augmented Exposure and Response Prevention Procedure in the Treatment of Obsessive-Compulsive Disorder: A Case Report

This case report describes the assessment and treatment of a 21-year-old male with obsessive-compulsive disorder (OCD) using an intensive exposure and response prevention (ERP) treatment program. The patient and his father received daily 2-hour ERP sessions delivered across 10 consecutive weekdays, and monthly follow-up appointments. In addition to the condensed treatment schedule, ERP procedures were augmented to address ongoing family conflict and depressive symptoms. To the best of the our knowledge, this is the first study to include such treatment adaptations within the context of intensive ERP for an adult with OCD. Results indicated target behaviors decreased over the 2-week intensive treatment phase and were maintained during 4 months of follow-up. Ancillary outcomes reported by the patient and his father included more frequent engagement in activities of daily living and improved family communication. Outcomes of this study provide an important step toward establishing recommendations regarding ERP session frequency, especially among patients with comorbid disorders.

American Society of Nephrology Kidney Tutored Research and Education for Kidney Scholars (TREKS) Program: A 10-Year Interim Analysis.

In response to decreasing numbers of individuals entering into nephrology fellowships, the American Society of Nephrology launched Kidney Tutored Research and Education for Kidney Scholars (TREKS) to stimulate interest in nephrology among medical students, graduate students, and postdoctoral fellows. The program combines a 1-week intensive exposure to kidney physiology with a longitudinal mentorship program at the participants' home institutions. Ten years in, an analysis was conducted to assess its effectiveness. We surveyed participants to assess their opinions regarding nephrology before and after the course and followed them longitudinally to determine their career choices. TREKS applicants who were not selected to participate were used as a comparison group. Three hundred eighty-one people participated in the program, and 242 completed the survey. After TREKS, both medical students and graduate students showed increased interest in nephrology, with rank scores of 5.6±0.2 before to 7.5±0.1 after the course for medical students (mean±SD, n =189, P = 0.001) and 7.3±0.3 to 8.7±0.3 ( n =53, P = 0.001) for graduate students. In long-term follow-up, TREKS medical students chose a nephrology pipeline residency at a higher rate than medical students overall (57% versus 31%, P = 0.01) and TREKS applicants who did not participate (47% versus 31%, P = 0.04). Nephrology fellowship rates for these groups exceeded the general population but did not significantly differ between TREKS participants and applicants. Doctor of Philosophy students and postdoctoral TREKS participants had a higher rate of participation in nephrology research compared with TREKS applicants (66% versus 30%, P = 0.01). In summary, the American Society of Nephrology Kidney TREKS program has demonstrated that it can increase interest in nephrology in the short term and increase the number of individuals going into nephrology careers. This long-term effect is most evident in Doctor of Philosophy students and postdoctoral participants. Further study is needed to assess the impact of TREKS on enrollment in nephrology fellowship programs.

Genetic evidence for involvement of β2-adrenergic receptor in brown adipose tissue thermogenesis in humans

BackgroundSympathetic activation of brown adipose tissue (BAT) thermogenesis can ameliorate obesity and related metabolic abnormalities. However, crucial subtypes of the β-adrenergic receptor (AR), as well as effects of its genetic variants on functions of BAT, remains unclear in humans. We conducted association analyses of genes encoding β-ARs and BAT activity in human adults.MethodsSingle nucleotide polymorphisms (SNPs) in β1-, β2-, and β3-AR genes (ADRB1, ADRB2, and ADRB3) were tested for the association with BAT activity under mild cold exposure (19 °C, 2 h) in 399 healthy Japanese adults. BAT activity was measured using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). To validate the results, we assessed the effects of SNPs in the two independent populations comprising 277 healthy East Asian adults using near-infrared time-resolved spectroscopy (NIRTRS) or infrared thermography (IRT). Effects of SNPs on physiological responses to intensive cold exposure were tested in 42 healthy Japanese adult males using an artificial climate chamber.ResultsWe found a significant association between a functional SNP (rs1042718) in ADRB2 and BAT activity assessed with FDG-PET/CT (p < 0.001). This SNP also showed an association with cold-induced thermogenesis in the population subset. Furthermore, the association was replicated in the two other independent populations; BAT activity was evaluated by NIRTRS or IRT (p < 0.05). This SNP did not show associations with oxygen consumption and cold-induced thermogenesis under intensive cold exposure, suggesting the irrelevance of shivering thermogenesis. The SNPs of ADRB1 and ADRB3 were not associated with these BAT-related traits.ConclusionsThe present study supports the importance of β2-AR in the sympathetic regulation of BAT thermogenesis in humans. The present collection of DNA samples is the largest to which information on the donor’s BAT activity has been assigned and can serve as a reference for further in-depth understanding of human BAT function.

Exposure of Peregrine Falcons to Halogenated Flame Retardants: A 30 Year Retrospective Biomonitoring Study across North America.

Compared to aquatic ecosystem, terrestrial systems have been subjected to fewer investigations on the exposure to halogenated flame retardants (HFRs). Our study utilized peregrine falcon eggs collected from multiple habitats across North America to retrospectively explore both spatial distribution and temporal changes in legacy (e.g., polybrominated diphenyl ethers) and alternative HFRs over a 30 year period (1984-2016). The results reveal intensive HFR exposure in terrestrial ecosystems and chemical-specific spatiotemporal distribution patterns. The correlations between egg levels of the selected HFRs and human population density clearly illustrated a significant urban influence on the exposure of this wildlife species to these HFRs and subsequent maternal transfer to their eggs. Temporal analyses suggest that, unlike aquatic systems, terrestrial ecosystems may undergo continual exposure to consistently high levels of legacy HFRs for a long period of time. Our findings collectively highlight the effectiveness of using peregrine eggs to monitor terrestrial exposure to HFRs and other bioaccumulative chemicals and the need for continuous monitoring of HFRs in terrestrial ecosystems.