Influences of resting-state intrinsic functional brain connectivity on the antidepressant treatment response in late-life depression.

BACKGROUND: Late-life depression (LLD) is characterized by differences in resting state functional connectivity within and between intrinsic functional networks. This study examined whether clinical improvement to antidepressant medications is associated with pre-randomization functional connectivity in intrinsic brain networks. METHODS: Participants were 95 elders aged 60 years or older with major depressive disorder. After clinical assessments and baseline MRI, participants were randomized to escitalopram or placebo with a two-to-one allocation for 8 weeks. Non-remitting participants subsequently entered an 8-week trial of open-label bupropion. The main clinical outcome was depression severity measured by MADRS. Resting state functional connectivity was measured between a priori key seeds in the default mode (DMN), cognitive control, and limbic networks. RESULTS: In primary analyses of blinded data, lower post-treatment MADRS score was associated with higher resting connectivity between: (a) posterior cingulate cortex (PCC) and left medial prefrontal cortex; (b) PCC and subgenual anterior cingulate cortex (ACC); (c) right medial PFC and subgenual ACC; (d) right orbitofrontal cortex and left hippocampus. Lower post-treatment MADRS was further associated with lower connectivity between: (e) the right orbitofrontal cortex and left amygdala; and (f) left dorsolateral PFC and left dorsal ACC. Secondary analyses associated mood improvement on escitalopram with anterior DMN hub connectivity. Exploratory analyses of the bupropion open-label trial associated improvement with subgenual ACC, frontal, and amygdala connectivity. CONCLUSIONS: Response to antidepressants in LLD is related to connectivity in the DMN, cognitive control and limbic networks. Future work should focus on clinical markers of network connectivity informing prognosis. REGISTRATION: ClinicalTrials.gov NCT02332291.

Preliminary Evidence That Cortical Amyloid Burden Predicts Poor Response to Antidepressant Medication Treatment in Cognitively Intact Individuals With Late-Life Depression.

OBJECTIVE: Amyloid accumulation, the pathological hallmark of Alzheimer's disease, may predispose some older adults to depression and cognitive decline. Deposition of amyloid also occurs prior to the development of cognitive decline. It is unclear whether amyloid influences antidepressant outcomes in cognitively intact depressed elders. DESIGN: A pharmacoimaging trial utilizing florbetapir (18F) PET scanning followed by 2 sequential 8-week antidepressant medication trials. PARTICIPANTS: Twenty-seven depressed elders who were cognitively intact on screening. MEASUREMENTS AND INTERVENTIONS: After screening, diagnostic testing, assessment of depression severity and neuropsychological assessment, participants completed florbetapir (18F) PET scanning. They were then randomized to receive escitalopram or placebo for 8 weeks in a double-blinded two-to-one allocation rate. Individuals who did not respond to initial treatment transitioned to a second open-label trial of bupropion for another 8 weeks. RESULTS: Compared with 22 amyloid-negative participants, 5 amyloid-positive participants exhibited significantly less change in depression severity and a lower likelihood of remission. In the initial blinded trial, 4 of 5 amyloid-positive participants were nonremitters (80%), while only 18% (4 of 22) of amyloid-negative participants did not remit (p = 0.017; Fisher's Exact test). In separate models adjusting for key covariates, both positive amyloid status (t = 3.07, 21 df, p = 0.003) and higher cortical amyloid binding by standard uptake value ratio (t = 2.62, 21 df, p = 0.010) were associated with less improvement in depression severity. Similar findings were observed when examining change in depression status across both antidepressant trials. CONCLUSIONS: In this preliminary study, amyloid status predicted poor antidepressant response to sequential antidepressant treatment. Alternative treatment approaches may be needed for amyloid-positive depressed elders.

Self-reported chemotherapy-related cognitive impairment compared with cognitive complaints following menopause.

OBJECTIVE: Cancer-related cognitive impairment (CRCI) is commonly reported following the administration of cancer treatment. Current longitudinal studies, primarily in women with breast cancer, suggest that up to 35% to 60% of patients exhibit persistent CRCI (pCRCI) following completion of chemotherapy. Complaints of subjective cognitive decline (SCD) are also commonly reported by women during and following the menopause transition in noncancer patients. Although the majority of evidence for cognitive difficulties in cancer patients and survivors is attributed to chemotherapy, there is growing evidence to suggest that menopausal status can also influence cognitive function in cancer patients. METHODS: Given that menopausal status may be contributing to pCRCI, we compared a group of primarily postmenopausal women with pCRCI to 2 groups of postmenopausal women: women who endorse menopause-associated SCD (maSCD+) and women who do not (maSCD-) to explore the similarities/differences between maSCD and pCRCI and the potential role of menopause in pCRCI. RESULTS: Persistent CRCI participants report more severe SCD symptoms than women after natural menopause, despite being on average 2.5-year postchemotherapy, supporting previous findings that CRCI can persist for months to years after completing treatment. Persistent CRCI participants not only endorsed greater SCD but also exhibited objective performance differences. In addition, pCRCI participants endorsed significantly greater menopausal symptoms compared with either maSCD group. Results were not related to menopausal status prior to chemotherapy or current endocrine therapy use. CONCLUSIONS: These results suggest that while menopausal symptoms may contribute to SCD experienced by cancer patients after chemotherapy, they do not fully account for pCRCI.

Cognitive Effects of Chemotherapy and Cancer-Related Treatments in Older Adults.

Advances in cancer treatment are producing a growing number of cancer survivors; therefore, issues surrounding quality of life during and following cancer treatment have become increasingly important. Chemotherapy-related cognitive impairment (CRCI) is a problem that is commonly reported following the administration of chemotherapy treatment in patients with cancer. Research suggests that CRCI can persist for months to years after completing treatment, which has implications for the trajectory of normal and pathologic cognitive aging for the growing number of long-term cancer survivors. These problems are particularly relevant for older individuals, given that cancer is largely a disease of older age, and the number of patients with cancer who are aged 65 years or older will increase dramatically over the coming decades. This review will briefly summarize empirical findings related to CRCI, discuss CRCI in older patients with cancer, propose potential causative hypotheses, and provide a canonical patient case to illustrate how CRCI presents clinically. Finally, potential intervention strategies for CRCI will be highlighted and issues to consider when evaluating older patients with a history of cancer will be discussed.

Mild cognitive impairment: diagnosis, longitudinal course, and emerging treatments.

Mild cognitive impairment (MCI) is widely regarded as the intermediate stage of cognitive impairment between the changes seen in normal cognitive aging and those associated with dementia. Elderly patients with MCI constitute a high-risk population for developing dementia, in particular Alzheimer's disease (AD). Although the core clinical criteria for MCI have remained largely unchanged, the operational definition of MCI has undergone several revisions over the course of the last decade and remains an evolving diagnosis. Prognostic implications of this diagnosis are becoming clearer with regard to the risk of progressive cognitive deterioration. Although patients with MCI may represent an optimal target population for pharmacological and non-pharmacological interventions, results from clinical trials have been mixed and an effective treatment remains elusive. This article provides a brief overview of the evolution of the concept of MCI and reviews current diagnostic criteria, the longitudinal course of the disorder, and current and emerging treatments for MCI.

Use of focused computerized cognitive training (Neuroflex) to improve symptoms in women with persistent chemotherapy-related cognitive impairment.

Purpose: Chemotherapy-related cognitive impairment (CRCI) is a distressing and increasingly recognized long-term sequela reported by breast cancer patients following cancer treatment. There is an urgent but unmet clinical need for treatments that improve CRCI. In this context, we proposed the use of a novel cognitive enhancement strategy called Neuroflex to target CRCI experienced by breast cancer survivors. Methods: The primary aim of this pilot study was to evaluate the feasibility and acceptability of Neuroflex, a novel digital cognitive enhancement strategy, in breast and gynecologic cancer survivors with CRCI. Secondary analyses focused on whether improvements in performance on Neuroflex were associated with improvement in subjective cognitive complaints and objective cognitive performance measures. Results: Participants (N = 21) completed an average of 7.42 hours of Neuroflex training per week, an average of 44.5 (±1.01) hours total, and had a 100% completion rate. Participants exhibited significant improvement in self-reported cognitive function as well as significant improvement on tasks of verbal learning and memory and auditory working memory. Participants also exhibited improvement in mood, as well as improvement on a disability assessment. Conclusions: Results demonstrate feasibility and that breast cancer survivors are capable of completing a lengthy and challenging cognitive training program. Secondly, Neuroflex may confer specific cognitive benefits to both self-reported and objective performance. Results strongly support further investigation of Neuroflex in a larger controlled trial to establish efficacy for CRCI symptoms. Further studies may also result in optimization of this digital intervention for women with CRCI.

In vitro bioevaluation and docking study of dihydrosphingosine and ethambutol analogues against sensitive and multi-drug resistant Mycobacterium tuberculosis.

Tuberculosis remains a major public health problem and one of the top ten causes of death worldwide. The alarming increase in multidrug-resistant and extensively resistant variants (MDR, pre-XDR, and XDR) makes the disease more difficult to treat and control. New drugs that act against MDR/XDR strains are needed for programs to contain this major epidemic. The present study aimed to evaluate new compounds related to dihydro-sphingosine and ethambutol against sensitive and pre-XDR Mycobacterium strains, as well as to characterize the pharmacological activity through in vitro and in silico approaches in mmpL3 protein. Of the 48 compounds analyzed, 11 demonstrated good to moderate activity on sensitive and MDR Mycobacterium tuberculosis (Mtb), with a Minimum Inhibitory Concentration (MIC) ranging from 1.5 to 8 µM. They presented 2 to 14 times greater potency of activity when compared to ethambutol in pre-XDR strain, and demonstrated a selectivity index varying between 2.21 and 82.17. The substance 12b when combined with rifampicin, showed a synergistic effect (FICI = 0.5) on sensitive and MDR Mtb. It has also been shown to have a concentration-dependent intracellular bactericidal effect, and a time-dependent bactericidal effect in M. smegmatis and pre-XDR M. tuberculosis. The binding mode of the compounds in its cavity was identified through molecular docking and using a predicted structural model of mmpL3. Finally, we observed by transmission electron microscopy the induction of damage to the cell wall integrity of M. tuberculosis treated with the substance 12b. With these findings, we demonstrate the potential of a 2-aminoalkanol derivative to be a prototype substance and candidate for further optimization of molecular structure and anti-tubercular activity in preclinical studies.

Listening to Stakeholders Involved in Speech-Language Therapy for Children With Communication Disorders: Content Analysis of Apple App Store Reviews.

BACKGROUND: With the plethora of mobile apps available on the Apple App Store, more speech-language pathologists (SLPs) have adopted apps for speech-language therapy services, especially for pediatric clients. App Store reviews are publicly available data sources that can not only create avenues for communication between technology developers and consumers but also enable stakeholders such as parents and clinicians to share their opinions and view opinions about the app content and quality based on user experiences. OBJECTIVE: This study examines the Apple App Store reviews from multiple key stakeholders (eg, parents, educators, and SLPs) to identify and understand user needs and challenges of using speech-language therapy apps (including augmentative and alternative communication [AAC] apps) for pediatric clients who receive speech-language therapy services. METHODS: We selected 16 apps from a prior interview study with SLPs that covered multiple American Speech-Language-Hearing Association Big Nine competencies, including articulation, receptive and expressive language, fluency, voice, social communication, and communication modalities. Using an automatic Python (Python Software Foundation) crawler developed by our research team and a Really Simple Syndication feed generator provided by Apple, we extracted a total of 721 app reviews from 2009 to 2020. Using qualitative coding to identify emerging themes, we conducted a content analysis of 57.9% (418/721) reviews and synthesized user feedback related to app features and content, usability issues, recommendations for improvement, and multiple influential factors related to app design and use. RESULTS: Our analyses revealed that key stakeholders such as family members, educators, and individuals with communication disorders have used App Store reviews as a platform to share their experiences with AAC and speech-language apps. User reviews for AAC apps were primarily written by parents who indicated that AAC apps consistently exhibited more usability issues owing to violations of design guidelines in areas of aesthetics, user errors, controls, and customization. Reviews for speech-language apps were primarily written by SLPs and educators who requested and recommended specific app features (eg, customization of visuals, recorded feedback within the app, and culturally diverse character roles) based on their experiences working with a diverse group of pediatric clients with a variety of communication disorders. CONCLUSIONS: To our knowledge, this is the first study to compile and analyze publicly available App Store reviews to identify areas for improvement within mobile apps for pediatric speech-language therapy apps from children with communication disorders and different stakeholders (eg, clinicians, parents, and educators). The findings contribute to the understanding of apps for children with communication disorders regarding content and features, app usability and accessibility issues, and influential factors that impact both AAC apps and speech-language apps for children with communication disorders who need speech therapy.

Subjective cognition and mood in persistent chemotherapy-related cognitive impairment.

PURPOSE: Persistent chemotherapy-related cognitive impairment (CRCI) is commonly reported following cancer treatment and negatively affects quality of life. While past research has focused on potential pathophysiological mechanisms underlying this relationship, the role of psychological factors, such as mood, stress, and anxiety, in the development of persistent CRCI has received less attention. As an additional analysis of data from a trial investigating the effects of transdermal nicotine patches on cognitive performance in patients with persistent CRCI, we examined whether change in mood was associated with changes in subjective and objective cognitive functioning. METHODS: Participants were randomized to either placebo (n = 11) or transdermal nicotine (n = 11) for 6 weeks, followed by 2 weeks of treatment withdrawal for a total of 8 weeks. Participants were assessed using behavioral, subjective, and objective measures of cognitive functioning and mood at five visits before, during, and after treatment. RESULTS: Although we did not detect an effect of treatment assignment on mood, over the course of the study, we observed a significant improvement on measures of mood that correlated with improvement in subjective and objective cognitive performance. CONCLUSIONS: We observed improvement in objective and subjective cognitive performance measures. These changes were associated with improvement in subsyndromal mood symptoms, likely resulting from participation in the trial itself. IMPLICATIONS FOR CANCER SURVIVORS: These results suggest that women with persistent CRCI may benefit from support and validation of their cognitive complaints, cognitive rehabilitation/therapies into their post-cancer care. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (trial registration: NCT02312943).

Benzimidazole and aminoalcohol derivatives show in vitro anthelmintic activity against Trichuris muris and Heligmosomoides polygyrus.

BACKGROUND: Infections by gastrointestinal nematodes cause significant economic losses and disease in both humans and animals worldwide. The discovery of novel anthelmintic drugs is crucial for maintaining control of these parasitic infections. METHODS: For this purpose, the aim of the present study was to evaluate the potential anthelmintic activity of three series of compounds against the gastrointestinal nematodes Trichuris muris and Heligmosomoides polygyrus in vitro. The compounds tested were derivatives of benzimidazole, lipidic aminoalcohols and diamines. A primary screening was performed to select those compounds with an ability to inhibit T. muris L1 motility by > 90% at a single concentration of 100 µM; then, their respective IC50 values were calculated. Those compounds with IC50 < 10 µM were also tested against the adult stage of T. muris and H. polygyrus at a single concentration of 10 µM. RESULTS: Of the 41 initial compounds screened, only compounds AO14, BZ6 and BZ12 had IC50 values < 10 µM on T. muris L1 assay, showing IC50 values of 3.30, 8.89 and 4.17 µM, respectively. However, only two of them displayed activity against the adult stage of the parasites: BZ12 killed 81% of adults of T. muris (IC50 of 8.1 µM) and 53% of H. polygyrus while BZ6 killed 100% of H. polygyrus adults (IC50 of 5.3 µM) but only 17% of T. muris. CONCLUSIONS: BZ6 and BZ12 could be considered as a starting point for the synthesis of further structurally related compounds.

Novel compound shows in vivo anthelmintic activity in gerbils and sheep infected by Haemonchus contortus.

The control of gastrointestinal nematodes in livestock is becoming increasingly difficult due to the limited number of available drugs and the rapid development of anthelmintic resistance. Therefore, it is imperative to develop new anthelmintics that are effective against nematodes. Under this context, we tested the potential toxicity of three compounds in mice and their potential anthelmintic efficacy in Mongolian gerbils infected with Haemonchus contortus. The compounds were selected from previous in vitro experiments: two diamine (AAD-1 and AAD-2) and one benzimidazole (2aBZ) derivatives. 2aBZ was also selected to test its efficacy in sheep. In Mongolian gerbils, the benzimidazole reduced the percentage of pre-adults present in the stomach of gerbils by 95% at a dose of 200 mg/kg. In sheep, there was a 99% reduction in the number of eggs shed in faeces after 7 days at a dose of 120 mg/kg and a 95% reduction in the number of worm adults present in the abomasum. In conclusion, 2aBZ could be considered a promising candidate for the treatment of helminth infections in small ruminants.

EEG as a Functional Marker of Nicotine Activity: Evidence From a Pilot Study of Adults With Late-Life Depression.

Late-life depression (LLD) is a debilitating condition that is associated with poor response to antidepressant medications and deficits in cognitive performance. Nicotinic cholinergic stimulation has emerged as a potentially effective candidate to improve cognitive performance in patients with cognitive impairment. Previous studies of nicotinic stimulation in animal models and human populations with cognitive impairment led to examining potential cognitive and mood effects of nicotinic stimulation in older adults with LLD. We report results from a pilot study of transdermal nicotine in LLD testing whether nicotine treatment would enhance cognitive performance and mood. The study used electroencephalography (EEG) recordings as a tool to test for potential mechanisms underlying the effect of nicotine. Eight non-smoking participants with LLD completed EEG recordings at baseline and after 12 weeks of transdermal nicotine treatment (NCT02816138). Nicotine augmentation treatment was associated with improved performance on an auditory oddball task. Analysis of event-related oscillations showed that nicotine treatment was associated with reduced beta desynchronization at week 12 for both standard and target trials. The change in beta power on standard trials was also correlated with improvement in mood symptoms. This pilot study provides preliminary evidence for the impact of nicotine in modulating cortical activity and improving mood in depressed older adults and shows the utility of using EEG as a marker of functional engagement in nicotinic interventions in clinical geriatric patients.

Anthelmintic activity of aminoalcohol and diamine derivatives against the gastrointestinal nematode Teladorsagia circumcincta.

Gastrointestinal nematodes (GIN) infections are a serious problem in livestock production due to the great economic losses they cause. Their control is increasingly difficult because of the rapid development of drug resistance and the limited number of available drugs. Therefore, this study evaluated 18 aminoalcohol and 16 diamine derivatives against eggs, first and third stage larvae from a susceptible and a resistant isolate of Teladorsagia circumcincta collected from sheep. The effectiveness of the in vitro anthelmintic activity of the compounds was evaluated using three different procedures: Egg Hatch Test (EHT), Larval Mortality Test (LMT) and Larval Migration Inhibition Test (LMIT). Those compounds with activities higher than 90 % in the initial screening at 50 µM were selected to determine their half maximal effective concentration (EC50). In parallel, cytotoxicity assays were conducted on Caco2 and HepG2 cell lines to calculate Selectivity Indexes (SI) for each compound. The diamine 30 presented the best results in preventing egg hatching, displaying the lowest EC50 value (1.01 ±â€¯0.04 µM) of all compounds tested and the highest SI (21.21 vs. Caco-2 cells). For the LMIT, the diamine 34 showed the highest efficacy, with EC50 values of 2.67 ±â€¯0.08 and 3.02 ±â€¯0.09 µM on the susceptible and resistant isolate of the parasite, respectively.

Persistent Intrinsic Functional Network Connectivity Alterations in Middle-Aged and Older Women With Remitted Depression.

BACKGROUND: In younger adults, residual alterations in functional neural networks persist during remitted depression. However, there are fewer data for midlife and older adults at risk of recurrence. Such residual network alterations may contribute to vulnerability to recurrence. This study examined intrinsic network functional connectivity in midlife and older women with remitted depression. METHODS: A total of 69 women (24 with a history of depression, 45 with no psychiatric history) over 50 years of age completed 3T fMRI with resting-state acquisition. Participants with remitted depression met DSM-IV-TR criteria for an episode in the last 10 years but not the prior year. Whole-brain seed-to-voxel resting-state functional connectivity analyses examined the default mode network (DMN), executive control network (ECN), and salience network (SN), plus bilateral hippocampal seeds. All analyses were adjusted for age and used cluster-level correction for multiple comparisons with FDR < 0.05 and a height threshold of p < 0.001, uncorrected. RESULTS: Women with a history of depression exhibited decreased functional connectivity between the SN (right insula seed) and ECN regions, specifically the left superior frontal gyrus. They also exhibited increased functional connectivity between the left hippocampus and the left postcentral gyrus. We did not observe any group differences in functional connectivity for DMN or ECN seeds. CONCLUSIONS: Remitted depression in women is associated with connectivity differences between the SN and ECN and between the hippocampus and the postcentral gyrus, a region involved in interoception. Further work is needed to determine whether these findings are related to functional alterations or are predictive of recurrence.

A bayesian approach to examining default mode network functional connectivity and cognitive performance in major depressive disorder.

To reconcile the inconsistency of the association between the resting-state functional connectivity (RSFC) and cognitive performance in healthy and depressed groups due to high variance of both measures, we proposed a Bayesian spatio-temporal model to precisely and accurately estimate the RSFC in depressed and nondepressed participants. This model was employed to estimate spatially-adjusted functional connectivity (saFC) in the extended default mode network (DMN) that was hypothesized to correlate with cognitive performance in both depressed and nondepressed. Multiple linear regression models were used to study the relationship between DMN saFC and cognitive performance scores measured in the following four cognitive domains while adjusting for age, sex, and education. In ROI pairs including the posterior cingulate (PCC) and anterior cingulate (ACC) cortex regions, the relationship between connectivity and cognition was found only with the Bayesian approach. Moreover, only the Bayesian approach was able to detect a significant diagnostic difference in the association in ROI pairs, including both PCC and ACC regions, due to smaller variance for the saFC estimator. The results confirm that a reliable and precise saFC estimator, based on the Bayesian model, can foster scientific discovery that may not be feasible with the conventional ROI-based FC estimator (denoted as 'AVG-FC').

Accelerated brain aging predicts impaired cognitive performance and greater disability in geriatric but not midlife adult depression.

Depression is associated with markers of accelerated aging, but it is unclear how this relationship changes across the lifespan. We examined whether a brain-based measure of accelerated aging differed between depressed and never-depressed subjects across the adult lifespan and whether it was related to cognitive performance and disability. We applied a machine-learning approach that estimated brain age from structural MRI data in two depressed cohorts, respectively 170 midlife adults and 154 older adults enrolled in studies with common entry criteria. Both cohorts completed broad cognitive batteries and the older subgroup completed a disability assessment. The machine-learning model estimated brain age from MRI data, which was compared to chronological age to determine the brain-age gap (BAG; estimated age-chronological age). BAG did not differ between midlife depressed and nondepressed adults. Older depressed adults exhibited significantly higher BAG than nondepressed elders (Wald χ2 = 8.84, p = 0.0029), indicating a higher estimated brain age than chronological age. BAG was not associated with midlife cognitive performance. In the older cohort, higher BAG was associated with poorer episodic memory performance (Wald χ2 = 4.10, p = 0.0430) and, in the older depressed group alone, slower processing speed (Wald χ2 = 4.43, p = 0.0354). We also observed a statistical interaction where greater depressive symptom severity in context of higher BAG was associated with poorer executive function (Wald χ2 = 5.89, p = 0.0152) and working memory performance (Wald χ2 = 4.47, p = 0.0346). Increased BAG was associated with greater disability (Wald χ2 = 6.00, p = 0.0143). Unlike midlife depression, geriatric depression exhibits accelerated brain aging, which in turn is associated with cognitive and functional deficits.

Nicotinic treatment of post-chemotherapy subjective cognitive impairment: a pilot study.

PURPOSE: Persistent chemotherapy-related cognitive impairment (pCRCI) is commonly reported following cancer treatment and negatively affects quality of life; however, there is currently no pharmacological treatment indicated for pCRCI. This pilot study obtained preliminary data regarding the use of transdermal nicotine patches as a therapeutic strategy for women with pCRCI to (1) reduce subjective cognitive complaints and (2) enhance objective cognitive performance in breast, colon, lymphoma, or ovarian cancer survivors with pCRCI. METHODS: Participants were randomized to either placebo (n = 11) or transdermal nicotine (n = 11) for 6 weeks, followed by 2 weeks of treatment withdrawal for a total of 8 weeks. Participants were assessed using both subjective and objective measures of cognitive functioning at five visits before, during, and after treatment. RESULTS: Over the course of the study, women in both groups improved substantially in severity of self-reported cognitive complaints measured by Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairments regardless of treatment arm. Additionally, objective cognitive performance measures improved in both groups; however, there was no significant difference in improvement between groups. CONCLUSIONS: Due to a large placebo response, we were unable to determine if a drug effect was present. However, we did observe substantial improvement in self-reported cognitive symptoms, likely resulting from factors related to participation in the trial rather than specific drug treatment effects. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (trial registration: NCT02312943). IMPLICATIONS FOR CANCER SURVIVORS: These results suggest that women with pCRCI can exhibit improvement in subjective cognition, with attention paid to symptoms and close follow-up over a short period of time.

El retorno a la universidad durante la pandemia: perspectivas de estudiantes de obstetricia de una universidad pública

Objetivo: Determinar la perspectiva del estudiante de obstetricia respecto al retorno de las actividades universitarias teóricas y prácticas en un contexto de pandemia. Materiales y métodos: Estudio analítico transversal, en el que participaron 115 estudiantes matriculados en la carrera de obstetricia (del segundo al quinto año) de una universidad pública de Lima. Se evaluó la proporción de estudiantes que están de acuerdo con el retorno a las actividades teóricas y prácticas, los recursos con los que cuentan y su situación familiar. Las asociaciones ajustadas fueron evaluadas mediante regresión de Poisson. Resultados: El 58,26 % [IC95 %: 48,93-67,03 %] de los participantes está de acuerdo con el retorno a las actividades teóricas virtuales; y el 6,09 % [IC95 %: 2,89-12,34 %], con el regreso a las prácticas hospitalarias. Solo el 66,09 % cuenta con internet, dispositivo móvil y un ambiente adecuado de estudio en su hogar. El grupo que no estuvo de acuerdo con el retorno a la práctica hospitalaria se caracterizó por presentar un antecedente patológico personal (p < 0,001) y convivir con dos o más personas mayores de 65 años (p < 0,001). Los principales antecedentes clínicos de los familiares mayores de 65 años fueron hipertensión arterial (36,89 %), diabetes (19,04 %) y obesidad (15,47 %). Conclusiones: Es escasa la proporción de estudiantes de obstetricia que están a favor del retorno a los hospitales, motivados principalmente por tener antecedentes patológicos personales y convivir con familiares mayores de 65 años. Cerca de la mitad de los participantes cuenta con recursos digitales que permiten su aprendizaje remoto.

Objective: To determine the perspectives of midwifery students regarding the return to the theoretical and practical university activities in the context of a pandemic. Materials and methods: A cross-sectional analytical study involving 115 second- to fifth-year midwifery students from a public university in Lima. The number of students who agreed to return to the theoretical and practical activities, the resources they had and their family situation were evaluated. Adjusted associations were estimated using Poisson regression. Results: Fifty-eight point two six percent (58.26 %) [95 % CI: 48.93 - 67.03 %] of the participants agreed to return to virtual theoretical activities and 6.09 % [95 % CI: 2.89 - 12,34 %] to hospital practical activities. Only 66.09 % had access to the Internet, a mobile device and an adequate study environment at home. Those who did not agree to return to the hospital practical activities had a history of a pathological condition (p < 0.001) and lived with two or more people over 65 years of age (p < 0.001). The main medical conditions of the relatives over 65 years of age were hypertension (36.89 %), diabetes (19.04 %) and obesity (15.47 %). Conclusions: The number of midwifery students who agreed to return to the hospitals was low mainly because they had a history of a pathological condition and lived with relatives over 65 years of age. About half of the participants had digital resources that allowed them to access to remote learning.

Altered Brain Connectivity in Early Postmenopausal Women with Subjective Cognitive Impairment.

Cognitive changes after menopause are a common complaint, especially as the loss of estradiol at menopause has been hypothesized to contribute to the higher rates of dementia in women. To explore the neural processes related to subjective cognitive complaints, this study examined resting state functional connectivity in 31 postmenopausal women (aged 50-60) in relationship to cognitive complaints following menopause. A cognitive complaint index was calculated using responses to a 120-item questionnaire. Seed regions were identified for resting state brain networks important for higher-order cognitive processes and for areas that have shown differences in volume and functional activity associated with cognitive complaints in prior studies. Results indicated a positive correlation between the executive control network and cognitive complaint score, weaker negative functional connectivity within the frontal cortex, and stronger positive connectivity within the right middle temporal gyrus in postmenopausal women who report more cognitive complaints. While longitudinal studies are needed to confirm this hypothesis, these data are consistent with previous findings suggesting that high levels of cognitive complaints may reflect changes in brain connectivity and may be a potential marker for the risk of late-life cognitive dysfunction in postmenopausal women with otherwise normal cognitive performance.

Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls.

The emergence of resting-state functional connectivity (rsFC) analysis, which examines temporal correlations of low-frequency (<0.1 Hz) blood oxygen level-dependent signal fluctuations between brain regions, has dramatically improved our understanding of the functional architecture of the typically developing (TD) human brain. This study examined rsFC in Down syndrome (DS) compared with another neurodevelopmental disorder, Williams syndrome (WS), and TD. Ten subjects with DS, 18 subjects with WS, and 40 subjects with TD each participated in a 3-Tesla MRI scan. We tested for group differences (DS vs. TD, DS vs. WS, and WS vs. TD) in between- and within-network rsFC connectivity for seven functional networks. For the DS group, we also examined associations between rsFC and other cognitive and genetic risk factors. In DS compared with TD, we observed higher levels of between-network connectivity in 6 out 21 network pairs but no differences in within-network connectivity. Participants with WS showed lower levels of within-network connectivity and no significant differences in between-network connectivity relative to DS. Finally, our comparison between WS and TD controls revealed lower within-network connectivity in multiple networks and higher between-network connectivity in one network pair relative to TD controls. While preliminary due to modest sample sizes, our findings suggest a global difference in between-network connectivity in individuals with neurodevelopmental disorders compared with controls and that such a difference is exacerbated across many brain regions in DS. However, this alteration in DS does not appear to extend to within-network connections, and therefore, the altered between-network connectivity must be interpreted within the framework of an intact intra-network pattern of activity. In contrast, WS shows markedly lower levels of within-network connectivity in the default mode network and somatomotor network relative to controls. These findings warrant further investigation using a task-based procedure that may help disentangle the relationship between brain function and cognitive performance across the spectrum of neurodevelopmental disorders.