Search

The current pre-/posttest pilot study investigated the impact of an individual nurse-led active listening intervention for spouses of individuals with depression (herein referred to as patients) on spouses' psychological states and patients' depressive symptoms. Sixteen couples participated in the study. Individual sessions were conducted over 10 weeks to help spouses express their thoughts and feelings. Psychological measurement scale scores did not change markedly postintervention for spouses; however, their subjective evaluations of the intervention were positive. In the qualitative analysis, spouses stated that they were able to express their thoughts and feelings and that the sessions were meaningful. Moreover, postintervention depressive scores of patients improved significantly. Findings suggest that the nurse-led intervention of active listening for spouses may provide a better environment for improving the depressive symptoms of patients. [ Journal of Psychosocial Nursing and Mental Health Services, xx (x), xx–xx.]

Background: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. Methods: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6–65) was divided into six successive 6–10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. Results: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6–13 and adults aged 50–65 with OCD taking SRIs (Cohen's d = −0.24 to −0.74). Volumes of putamen, pallidum (d = 0.18–0.40), and ventricles (d = 0.31–0.66) were greater in patients aged 20–29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = −0.27 to −1.31). Conclusions: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20–29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.

Objective Acute kidney injury (AKI) in the neonatal period is associated with worst outcomes as increased mortality and increased length of hospital stay. Very low birth weight (VLBW) newborns are at higher risk for developing several other conditions that are associated with worst outcomes. Understanding the risk factors for AKI may help to prevent this condition and improve neonatal care for this population. Methods This retrospective cohort study included 155 very low birth weight newborns admitted between 2015 and 2017. The authors compared the newborns who developed neonatal AKI with the non-AKI group and analyzed the main risk factors for developing AKI in the population. The authors also performed an analysis of the main outcomes defined as the duration of mechanical ventilation, length of stay, and death. Results From the cohort, a total of 61 (39.4%) patients had AKI. The main risk factors associated with Neonatal AKI were necrotizing enterocolitis (aOR 7.61 [1.69 - 34.37]; p = 0.008), neonatal sepsis (aOR 2.91 [1.17 - 7.24], p = 0.021), and hemodynamic instability (aOR 2.99 [1.35 - 6.64]; p = 0.007). Neonatal AKI was also associated with an increase in the duration of mechanical ventilation in 9.4 days (p = 0.026) and in an increase in mortality 4 times (p = 0.009), after adjusting for the other variables. Conclusion The present results highlight the importance of minimizing sepsis and necrotizing enterocolitis, as well as the importance of identifying hemodynamic instability, to prevent AKI and diminish the burden of morbimortality in VLBW newborns.

To understand how sleep-wakefulness cycles are regulated, it is essential to disentangle structural and functional relationships between the preoptic area (POA) and lateral hypothalamic area (LHA), since these regions play important yet opposing roles in the sleep-wakefulness regulation. GABA- and galanin (GAL)-producing neurons in the ventrolateral preoptic nucleus (VLPO) of the POA (VLPOGABAand VLPOGALneurons) are responsible for the maintenance of sleep, while the LHA contains orexin-producing neurons (orexin neurons) that are crucial for maintenance of wakefulness. Through the use of rabies virus-mediated neural tracing combined within situhybridization (ISH) in male and femaleorexin-iCremice, we revealed that the vesicular GABA transporter (Vgat, Slc32a1)- and galanin (Gal)-expressing neurons in the VLPO directly synapse with orexin neurons in the LHA. A majority (56.3 ± 8.1%) of all VLPO input neurons connecting to orexin neurons were double-positive forVgatandGal. Using projection-specific rabies virus-mediated tracing in male and femaleVgat-ires-CreandGal-Cremice, we discovered that VLPOGABAand VLPOGALneurons that send projections to the LHA received innervations from similarly distributed input neurons in many brain regions, with the POA and LHA being among the main upstream areas. Additionally, we found that acute optogenetic excitation of axons of VLPOGABAneurons, but not VLPOGALneurons, in the LHA of maleVgat-ires-Cremice induced wakefulness. This study deciphers the connectivity between the VLPO and LHA, provides a large-scale map of upstream neuronal populations of VLPO→LHA neurons, and reveals a previously uncovered function of the VLPOGABA→LHA pathway in the regulation of sleep and wakefulness.SIGNIFICANCE STATEMENTWe identified neurons in the ventrolateral preoptic nucleus (VLPO) that are positive for vesicular GABA transporter (Vgat) and/or galanin (Gal) and serve as presynaptic partners of orexin-producing neurons in the lateral hypothalamic area (LHA). We depicted monosynaptic input neurons of GABA- and galanin-producing neurons in the VLPO that send projections to the LHA throughout the entire brain. Their input neurons largely overlap, suggesting that they comprise a common neuronal population. However, acute excitatory optogenetic manipulation of the VLPOGABA→LHA pathway, but not the VLPOGAL→LHA pathway, evoked wakefulness. This study shows the connectivity of major components of the sleep/wake circuitry in the hypothalamus and unveils a previously unrecognized function of the VLPOGABA→LHA pathway in sleep-wakefulness regulation. Furthermore, we suggest the existence of subpopulations of VLPOGABAneurons that innervate LHA.

Medidas de mitigação do contágio pelo coronavírus ocasionaram redução de atendimentos presenciais na Atenção Primária à Saúde. A telessaúde possibilita a manutenção da continuidade do cuidado nesse contexto. Diante disso, objetivou-se conhecer a perspectiva de usuários e profissionais de saúde acerca da telessaúde em uma região de fronteira, durante a pandemia de 2019. Trata-se de um estudo qualitativo, descritivo-exploratório, realizado com usuários e profissionais de saúde da Atenção Primária de Foz do Iguaçu, Paraná, Brasil, nos meses de agosto a dezembro de 2020. A coleta de dados ocorreu por ligação de voz com o registro por audiogravação cuja análise ocorreu por meio da Análise de Conteúdo. Os resultados contemplaram as categorias: Telessaúde: implantação e organização; Telessaúde: pontos positivos; Telessaúde: dificuldades e ações para a sua manutenção; Telessaúde na região de fronteira. Apesar das dificuldades vivenciadas, a telessaúde mostrou-se complementar ao atendimento presencial e tende a ser mantida no contexto do estudo após a pandemia.

Tropical peatlands cycle and store large amounts of carbon in their soil and biomass1–5. Climate and land-use change alters greenhouse gas (GHG) fluxes of tropical peatlands, but the magnitude of these changes remains highly uncertain6–19. Here we measure net ecosystem exchanges of carbon dioxide, methane and soil nitrous oxide fluxes between October 2016 and May 2022 from Acacia crassicarpa plantation, degraded forest and intact forest within the same peat landscape, representing land-cover-change trajectories in Sumatra, Indonesia. This allows us to present a full plantation rotation GHG flux balance in a fibre wood plantation on peatland. We find that the Acacia plantation has lower GHG emissions than the degraded site with a similar average groundwater level (GWL), despite more intensive land use. The GHG emissions from the Acacia plantation over a full plantation rotation (35.2 ± 4.7 tCO2-eq ha−1 year−1, average ± standard deviation) were around two times higher than those from the intact forest (20.3 ± 3.7 tCO2-eq ha−1 year−1), but only half of the current Intergovernmental Panel on Climate Change (IPCC) Tier 1 emission factor (EF)20 for this land use. Our results can help to reduce the uncertainty in GHG emissions estimates, provide an estimate of the impact of land-use change on tropical peat and develop science-based peatland management practices as nature-based climate solutions.

Aspiration pneumonia is one of the leading causes of death in patients with muscular dystrophy; therefore, it is important to predict its occurrence in the clincal setting. We aimed to examine the usefulness of repeated saliva swallowing test (RSST), modified water swallowing test (MWST), and flexible endoscopic evaluation of swallowing (FEES) for evaluating the Hyodo score at the bedside, to predict the risk of aspiration pneumonia in patients with Duchenne muscular dystrophy (DMD).In this retrospective cohort study involving 43 patients, we evaluated the swallowing function using the RSST, MWST, and FEES, and predicted the likelihood of aspiration pneumonia within 2 years after the assessment. The Hyodo score, a scoring system for evaluating the swallowing function determined by the FEES, was used.Pneumonia was observed in 14 patients (32.6%). The RSST was not significantly useful for predicting the onset of pneumonia. The MWST was reported to have a cutoff value of4 points. Significantly more patients in the pneumonia group had an MWST score of4 points. The results revealed that the occurrence of pneumonia could be predicted based on a Hyodo cutoff score of ≥ 6. Significantly more patients in the pneumonia group had an MWST score of4 or a Hyodo score of ≥ 6.Combining MWST and FEES is useful for evaluating the bedside swallowing function and predicting the onset of pneumonia.

Eosinophilic gastrointestinal (GI) disorders are a group of conditions marked by pathologic eosinophilic infiltration of one or multiple locations in the GI tract. Conditions include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic enteritis, and eosinophilic colitis. The site and depth of eosinophilic infiltration of the GI tract usually determines clinical presentation. These conditions should be considered in the differential diagnosis for several GI symptoms, such as food impaction or dysphagia. Histopathology is the gold standard for diagnosis of eosinophilic disorders. Nevertheless, findings from endoscopy, barium studies, computed tomography or magnetic resonance imaging, can aid in the diagnosis, by allowing for earlier diagnosis as well as proper management. Eosinophilic gastrointestinal disorders are typically managed with corticosteroids or dietary elimination. A high index of suspicion is required for diagnosis as it can often be challenging.

[Introduction] Proliferative lesions in the breast have been implicated in the development of breast cancer. Previous studies showed that some proliferative lesions and adjacent breast cancers shared common genetic alterations, suggesting that these originated from the same ancestral cell. However, the clonal structure of normal epithelia and their clonal history during evolution to cancer are poorly understood. In this study, we analyzed genetic profiles of normal epithelia and proliferative lesions in the cancer-borne breast to illustrate the clonal evolution of cancer from a normal epithelial cell. [Methods] Single cell-derived organoids (n=47) were established from breast milk of 4 healthy women aged 22–36 and normal breast tissue of 15 breast cancer patients aged 29–83 to evaluate somatic mutation rate in normal epithelial cells. Multiple normal lobules and proliferative lesions together with cancer lesions were collected using laser-capture micro-dissection (LCM) from fresh frozen (n=3) or formalin-fixed paraffin-embedded (n=5) surgical specimens in 9 premenopausal breast cancer patients. Somatic mutations and copy number alterations were evaluated using whole-genome sequencing. [Results] The mutation profile of single cell-derived organoids suggests that somatic mutations accumulate in normal mammary epithelial cells at a constant rate of 19.4/genome/year before menopause, and the mutation rate decreases to 6.9/genome/year after menopause. Parity was negatively associated with mutation number (-49.3 per life birth). In total, we analyzed 143 LCM samples, including those from 72 normal lobules, 43 proliferative lesions, and 19 non-invasive and 9 invasive cancer samples. Five cases showed a large expansion of proliferative lesions sharing a substantial number of somatic mutations with cancer. These lesions expanded over a distance of 35-90 mm, sharing tens to hundreds of mutations including those in breast cancer-related driver genes, such as PIK3CA, AKT1, GATA3, CBFB and PTEN, while harboring private mutations or copy number alterations of their own. Of interest, the cancers in 4 out of these 5 cases was luminal-A type invasive ducal carcinoma or ER-positive HER2-negative ductal carcinoma in situ, and characterized in common by the presence of der(1;16), concurrent whole-arm 1q gain and 16q loss, in both cancer and proliferative lesions. Phylogenetic analysis adapted with the mutation rate in normal cells predicted that der(1;16) had been acquired between puberty and early 20’s, and the common ancestors of non-cancerous and cancerous lesions emerged by early 30’s, >10 years earlier than at the time of cancer diagnosis. By contrast, analysis of non-cancerous lobules unrelated to cancer showed that der(1;16)-negative non-cancer clones that had emerged after puberty stayed within a single lobule or spatially confined to adjacent lobules and rarely expanded to a large area as observed for those carrying der(1;16), even if the clones had acquired mutations in driver genes such as PIK3CA and PIK3R1, which highlighted the role of der(1;16) in wide clonal expansion. [Conclusions] Our results suggest that in some breast cancer cases, particularly in those with der(1;16), a highly recurrent translocation accounting for the major subset of Luminal A breast cancer, the clones with the funder driver alterations expanded macroscopically long before the onset of cancer, in which further clonal evolutions recursively occur multi-focally, giving rise to multiple proliferative lesions and ultimately, invasive cancers. Our findings provide new insight into the early development of breast cancer. Citation Format: Tomomi Nishimura, Nobuyuki Kakiuchi, Kenichi Yoshida, Takaki Sakurai, Tatsuki R. Kataoka, Eiji Kondoh, Yoshitsugu Chigusa, Masahiko Kawai, Morio Sawada, Takuya Inoue, Yasuhide Takeuchi, Hirona Maeda, Satoko Baba, Yusuke Shiozawa, Ryunosuke Saiki, Masahiro M. Nakagawa, Yasuhito Nannya, Yotaro Ochi, Tomonori Hirano, Yukiko Inagaki-Kawata, Kosuke Aoki, Masahiro Hirata, Eiji Suzuki, Masahiro Takada, Masahiro Kawashima, Kosuke Kawaguchi, Kenichi Chiba, Yuichi Shiraishi, Junko Takita, Satoru Miyano, Masaki Mandai, Kengo Takeuchi, Hironori Haga, Masakazu Toi, Seishi Ogawa. Clonal evolution of mammary epithelial cells into breast cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-13-04.

Increasing spike rates drive greater neuronal energy demand. In turn, mitochondrial ATP production leads to the generation of reactive oxygen species (ROS) that can modulate ion channel gating. Does ROS production autoregulate the excitability of a neuron? We investigated the links between retinal ganglion cell (RGC) excitability and spike activity-driven ROS production in male and female mice. Changes to the light-evoked and current-evoked spike patterns of functionally identified αRGC subtypes, along with their NaVchannel-gating properties, were recorded during experimentally induced decreases and increases of intracellular ROS. During periods of highest spike rates (e.g., following light onset in ON sustained RGCs and light offset in OFF sustained RGCs), these αRGC subtypes responded to reductions of ROS (induced by catalase or glutathione monoethyl ester) with higher spike rates. Increases in ROS (induced by mercaptosuccinate, antimycin-A, or H2O2) lowered spike rates. In ON and OFF transient RGCs, there were no changes in spike rate during ROS decreases but increased ROS increased spiking. This suggests that endogenous ROS are intrinsic neuromodulators in RGCs having high metabolic demands but not in RGCs with lower energy needs. We identified ROS-induced shifts in the voltage-dependent gating of specific isoforms of NaVchannels that account for the modulation of ON and OFF sustained RGC spike frequency by ROS-mediated feedback. ROS-induced changes to NaVchannel gating, affecting activation and inactivation kinetics, are consistent with the differing spike pattern alterations observed in RGC subtypes. Cell-autonomous generation of ROS during spiking contributes to tuning the spike patterns of RGCs.SIGNIFICANCE STATEMENTEnergy production within retinal ganglion cells (RGCs) is accompanied by metabolic by-products harmful to cellular function. How these by-products modulate the excitability of RGCs bears heavily on visual function and the etiology of optic neuropathies. A novel hypothesis of how RGC metabolism can produce automodulation of electrical signaling was tested by identifying the characteristics and biophysical origins of changes to the excitability of RGCs caused by oxidizing by-products in the retina. This impacts our understanding of the pathophysiology of RGC dysfunction, supporting an emerging model in which increases in oxidizing chemical species during energy production, but not necessarily bioenergetic failure, lead to preferential degeneration of specific subtypes of RGCs, yielding loss of different aspects of visual capacity.