Changes in TgAb and TPOAb titers are greater in thyrotoxicosis than isolated hypothyroidism induced by PD-1 blockade.

Anti-thyroglobulin antibodies (TgAb) and/or anti-thyroid peroxidase antibodies (TPOAb) positivity at baseline is a risk marker for thyroid immune-related adverse events (thyroid-irAEs) in anti-programmed cell death-1 antibody (PD-1-Ab) treatment; however, it is unknown if TgAb and TPOAb titers are associated with clinical characteristics of thyroid-irAEs. Among 586 patients treated with PD-1-Ab at Nagoya University Hospital between 2 November 2015 and 30 September 2021, 57 patients developed thyroid-irAEs (thyrotoxicosis [n = 38]; hypothyroidism without prior thyrotoxicosis {isolated hypothyroidism} [n = 19]) in whom thyroid function, and TgAb and TPOAb titers were determined at baseline and at the onset. The changes in TgAb (median, 54.8 vs. 0.2 IU/mL; p = 0.002) and TPOAb titers (31.6 vs. 0 IU/mL; p = 0.032) from baseline to onset of developing thyroid-irAEs were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism. Higher TgAb and TPOAb titers, and the TgAb titer at baseline were associated with an earlier onset of thyrotoxicosis and higher peak free thyroxine levels, respectively. Twenty-eight patients who developed hypothyroidism after thyrotoxicosis had higher TgAb (54.5 vs. 10.7 IU/mL; p = 0.011) and TPOAb titers at baseline (46.1 vs. 9.0 IU/mL; p < 0.001) and greater changes in TgAb (61.7 vs. 7.8 IU/mL; p = 0.025) and TPOAb titers (52.8 vs. -0.8 IU/mL; p < 0.001) than patients who did not develop hypothyroidism. The TgAb titer at baseline and changes in the TgAb and TPOAb titers were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism, suggesting that the magnitude of the thyroid autoimmune response reflects the clinical types of thyroid-irAEs.

Genomic diversity of the pathogenic fungus Aspergillus fumigatus in Japan reveals the complex genomic basis of azole resistance.

Aspergillus fumigatus is a pathogenic fungus with a global distribution. The emergence of azole-resistant A. fumigatus (ARAf) other than the TR-mutants is a problem in Japan. Additionally, the genetic diversity of A. fumigatus strains in Japan remains relatively unknown. Here we show the diversity in the A. fumigatus strains isolated in Japan as well as the complexity in the global distribution of the pathogenic strains. First, we analyzed the genome sequences of 171 strains from Japan as well as the antifungal susceptibility of these strains. Next, we conducted a population analysis of 876 strains by combining the available genomic data for strains isolated worldwide, which were grouped in six clusters. Finally, a genome-wide association study identified the genomic loci associated with ARAf strains, but not the TR-mutants. These results highlight the complexity of the genomic mechanism underlying the emergence of ARAf strains other than the TR-mutants.

Isolation of azole-resistant Aspergillus spp. from food products.

The prevalence of azole-resistant Aspergillus fumigatus is increasing worldwide and is speculated to be related to the use of azole pesticides. Aspergillus spp., the causative agent of aspergillosis, could be brought into domestic dwellings through food. However, studies on azole-resistant Aspergillus spp. in food products are limited. Therefore, we aimed to isolate Aspergillus spp. from processed foods and commercial agricultural products and performed drug susceptibility tests for azoles. Among 692 food samples, we isolated 99 strains of Aspergillus spp. from 50 food samples, including vegetables (22.9%), citrus fruits (26.3%), cereals (25.5%), and processed foods (1.8%). The isolates belonged to 18 species across eight sections: Aspergillus, Candidi, Clavati, Flavi, Fumigati, Nidulantes, Nigri, and Terrei. The most frequently isolated section was Fumigati with 39 strains, followed by Nigri with 28 strains. Aspergillus fumigatus and A. welwitschiae were the predominant species. Ten A. fumigatus and four cryptic strains, four A. niger cryptic strains, two A. flavus, and four A. terreus strains exceeded epidemiological cutoff values for azoles. Aspergillus tubingensis, A. pseudoviridinutans, A. lentulus, A. terreus, and N. hiratsukae showed low susceptibility to multi-azoles. Foods containing agricultural products were found to be contaminated with Aspergillus spp., with 65.3% of isolates having minimal inhibitory concentrations below epidemiological cutoff values. Additionally, some samples harbored azole-resistant strains of Aspergillus spp. Our study serves as a basis for elucidating the relationship between food, environment, and clinically important Aspergillus spp.

A machine learning approach for predicting treatment response of hyponatremia.

Hyponatremia leads to severe central nervous system disorders and requires immediate treatment in some cases. However, a rapid increase in serum sodium (s-Na) concentration could cause osmotic demyelination syndrome. To achieve a safety hyponatremia treatment, we develop a prediction model of s-Na concentration using a machine learning. Among the 341 and 47 patients admitted to two tertiary hospitals for hyponatremia treatment (s-Na <130 mEq/L), those who were admitted to the general unit with urine sodium <20 mEq/L or treated with desmopressin were excluded. Ultimately, 74 and 15 patients (342 and 146 6-hourly datasets) were included in the learning and validation data, respectively. We trained the prediction model using three regression algorithms for shallow machine learning to predict s-Na every 6 h during treatment with the data of patients with hyponatremia (median s-Na: 112.5 mEq/L; range: 110.0-116.8 mEq/L) from one hospital. The model was validated externally using the data of patients with hyponatremia (median s-Na: 117.0 mEq/L; range: 112.9-120.0 mEq/L) from another hospital. Using 5-7 predictors (water intake, sodium intake, potassium intake, urine volume, s-Na concentration, serum potassium concentration, serum chloride concentration), the support vector regression model showed the best performance overall (root mean square error = 0.05396; R2 = 0.92), followed by the linear regression and regression tree models. The predicted s-Na levels, using explainable machine learning algorithms and clinically accessible parameters, correlated well with the actual levels. Thus, our model could be applied to the treatment of hyponatremia in clinical practice.

Simplified drug efficacy evaluation system for vasopressin neurodegenerative disease using mouse disease-specific induced pluripotent stem cells.

Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disorder in which vasopressin-secreting neurons degenerate over time due to the production of mutant proteins. We have demonstrated therapeutic effects of chemical chaperones in an FNDI mouse model, but the complexity and length of this evaluation were problematic. In this study, we established disease-specific mouse induced pluripotent stem cells (iPSCs) from FNDI-model mice and differentiated vasopressin neurons that produced mutant proteins. Fluorescence immunostaining showed that chemical chaperones appeared to protect vasopressin neurons generated from iPSCs derived from FNDI-model mice. Although KCL stimulation released vasopressin hormone from vasopressin neurons generated from FNDI-derived iPSCs, vasopressin hormone levels did not differ significantly between baseline and chaperone-added culture. Semi-quantification of vasopressin carrier protein and mutant protein volumes in vasopressin neurons confirmed that chaperones exerted a therapeutic effect. This research provides fundamental technology for creating in vitro disease models using human iPSCs and can be applied to therapeutic evaluation of various degenerative diseases that produce abnormal proteins.

Effects of Digitization of Self-Monitoring of Blood Glucose Records Using a Mobile App and the Cloud System on Outpatient Management of Diabetes: Single-Armed Prospective Study.

BACKGROUND: In recent years, technologies promoting the digitization of self-monitoring of blood glucose (SMBG) records including app-cloud cooperation systems have emerged. Studies combining these technological interventions with support from remote health care professionals have reported improvements in glycemic control. OBJECTIVE: To assess the use of an app-cloud cooperation system linked with SMBG devices in clinical settings, we evaluated its effects on outpatient management of diabetes without remote health care professional support. METHODS: In this multicenter, open-label, and single-armed prospective study, 48 patients with diabetes (including type 1 and type 2) at 3 hospitals in Japan treated with insulin or glucagon-like peptide 1 receptor agonists and performing SMBG used the app-cloud cooperation system for 24 weeks. The SMBG data were automatically uploaded to the cloud via the app. The patients could check their data, and their attending physicians reviewed the data through the cloud prior to the patients' regular visits. The primary outcome was changes in glycated hemoglobin (HbA1c) levels. RESULTS: Although HbA1c levels did not significantly change in all patients, the frequency of daily SMBG following applying the system was significantly increased before induction at 12 (0.60 per day, 95% CI 0.19-1.00; P=.002) and 24 weeks (0.43 per day, 95% CI 0.02-0.84; P=.04). In the subset of 21 patients whose antidiabetic medication had not been adjusted during the intervention period, a decrease in HbA1c level was observed at 12 weeks (P=.02); however, this significant change disappeared at 24 weeks (P=.49). The Diabetes Treatment Satisfaction Questionnaire total score and "Q4: convenience" and "Q5: flexibility" scores significantly improved after using the system (all P<.05), and 72% (33/46) patients and 76% (35/46) physicians reported that the app-cloud cooperation system helped them adjust insulin doses. CONCLUSIONS: The digitization of SMBG records and sharing of the data by patients and attending physicians during face-to-face visits improved self-management in patients with diabetes. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) jRCTs042190057; https://jrct.niph.go.jp/en-latest-detail/jRCTs042190057.

Seven new mycoviruses identified from isolated ascomycetous macrofungi.

Mycoviruses have been described in all major fungal taxonomic groups. There has been much focus on commercially cultivated basidiomycetous macrofungi, while attention to viruses from ascomycetous macrofungi is lacking. Therefore, in this study, we conducted viral screening against fungal mycelia that were regenerated from ascomycetous macrofungi using agarose gel electrophoresis (AGE) and fragmented and primer-ligated dsRNA sequencing (FLDS). Among the 57 isolates, four isolates were detected with virus-like bands through screening with AGE, and subsequent FLDS analyses determined the viral sequences. Other isolates without virus-like bands in AGE were pooled to check for viral sequences. Using FLDS analysis, a total of seven new mycoviruses were identified, including two double-stranded RNA (dsRNA) viruses belonging to Quadriviridae and Partitiviridae, five positive-sense single-stranded RNA (ssRNA) viruses (three belonging to Mitoviridae, one belonging to Endornaviridae and one belonging to Virgaviridae). All viruses characterized in this study are novel species, and all the hosts are firstly reported to be infected by mycoviruses. These findings expand our knowledge of the diversity of mycoviruses from macrofungi in natural environments.

A retrospective study on tolvaptan prescription in clinical practice in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) using the Japanese claims database.

We aimed to survey the status of tolvaptan administration in routine clinical practice since the approval of a novel indication for treating syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in Japan. Data from a population of 3,152 patients aged ≥18 years and diagnosed with SIADH between July 1, 2020 and June 30, 2021 were extracted from a Japanese database. Tolvaptan was administered to 586 patients while 2,566 patients were followed up without tolvaptan. In the tolvaptan-treated group, the standard initial doses were 3.75 mg and 7.5 mg in 290 (49.5%) and 250 (42.7%) patients, respectively. The dose was increased in 112 (38.6%) and 71 (28.4%) and decreased in 8 (2.8%) and 46 (18.4%) of patients with 3.75 and 7.5 mg initial doses, respectively. Of the total 586 SIADH patients treated with tolvaptan, serum sodium concentrations were analyzed in 60 patients. In both treatment groups of 3.75 and 7.5 mg initial doses, the serum sodium concentration was elevated from the second day of treatment and reached 135 mEq/L on the fourth day, which was maintained for 2 weeks. Rapid correction of hyponatremia (>10 mEq/L increase in serum sodium concentration over 1 day or >18 mEq/L increase over 2 days) occurred in 26.7% patients with a 7.5 mg initial dose (4 of 15 patients) but not in the patients with a 3.75 mg initial dose (n = 16), suggesting that an initial dose of 3.75 mg of tolvaptan may be a better choice for the safe and proper correction of hyponatremia.

Improved glycemic control after the use of flash glucose monitoring accompanied by improved treatment satisfaction in patients with non-insulin-treated type 2 diabetes: A post-hoc analysis of a randomized controlled trial.

AIMS: In our previously reported randomized controlled trial in patients with noninsulin-treated type 2 diabetes, the use of flash glucose monitoring (FGM) improved glycated hemoglobin (HbA1c), and the improvement was sustained after the cessation of glucose monitoring. In this post-hoc analysis, we examined data from our trial to identify the factors that influenced FGM efficacy. METHODS: We analyzed data for 48 of 49 participants of the FGM group who completed the trial to clarify the changes in various parameters and factors related to HbA1c improvement with the use of FGM. RESULTS: Analyses of the FGM data during the 12-week FGM provision period showed that the weekly mean blood glucose levels considerably decreased as early as at 1 week compared with the baseline values, and this decline continued for 12 weeks. An enhancement in the Diabetes Treatment Satisfaction Questionnaire regarding "willingness to continue the current treatment" score was significantly associated with the improvement in HbA1c at 12 (p = 0.009) and 24 weeks (p = 0.012). CONCLUSIONS: Glycemic control was improved soon after FGM initiation, accompanied by improved satisfaction with continuation of the current treatment in patients with noninsulin-treated type 2 diabetes.

Experimental verification of strain-dependent relationship between mycovirus and its fungal host.

Mycoviruses are viruses that infect fungi. Unlike mammalian infectious viruses, their life cycle does not generally have an extracellular stage, and a symbiosis-like relationship is maintained between virus and host fungi. Recently, mycoviruses have been reported to show effects on host fungi, altering biological properties such as growth rate, virulence, drug resistance, and metabolite production. In this study, we systematically elucidated the effects of viruses on host cells by comparing host phenotypes and transcriptomic responses in multiple sets of virus-infected and -eliminated Aspergillus flavus strains. The comparative study showed that mycoviruses affect several cellular activities at the molecular level in a virus- and host strain-dependent manner. The virus-swapping experiment revealed that difference with only three bases in the virus genome led to different host fungal response at the transcriptional level. Our results highlighted highly specific relationship between viruses and their host fungi.

Generation and purification of ACTH-secreting hPSC-derived pituitary cells for effective transplantation.

Pituitary organoids are promising graft sources for transplantation in treatment of hypopituitarism. Building on development of self-organizing culture to generate pituitary-hypothalamic organoids (PHOs) using human pluripotent stem cells (hPSCs), we established techniques to generate PHOs using feeder-free hPSCs and to purify pituitary cells. The PHOs were uniformly and reliably generated through preconditioning of undifferentiated hPSCs and modulation of Wnt and TGF-ß signaling after differentiation. Cell sorting using EpCAM, a pituitary cell-surface marker, successfully purified pituitary cells, reducing off-target cell numbers. EpCAM-expressing purified pituitary cells reaggregated to form three-dimensional pituitary spheres (3D-pituitaries). These exhibited high adrenocorticotropic hormone (ACTH) secretory capacity and responded to both positive and negative regulators. When transplanted into hypopituitary mice, the 3D-pituitaries engrafted, improved ACTH levels, and responded to in vivo stimuli. This method of generating purified pituitary tissue opens new avenues of research for pituitary regenerative medicine.

Response to endoplasmic reticulum stress in arginine vasopressin neurons.

Arginine vasopressin (AVP) is an antidiuretic hormone synthesized principally in the hypothalamic supraoptic and paraventricular nuclei. The immunoglobulin heavy chain binding protein (BiP), one of the most abundant endoplasmic reticulum (ER) chaperones, is highly expressed in AVP neurons, even under basal conditions. Moreover, its expression is upregulated in proportion to the increase in AVP expression under dehydration. These data suggest that AVP neurons are constantly exposed to ER stress. BiP knockdown in AVP neurons induces ER stress and autophagy, resulting in AVP neuronal loss, indicating that BiP is pivotal in maintaining the AVP neuron system. Furthermore, inhibition of autophagy after BiP knockdown exacerbates AVP neuronal loss, suggesting that autophagy induced under ER stress is a protective cellular mechanism by which AVP neurons cope with ER stress. Familial neurohypophysial diabetes insipidus (FNDI) is an autosomal dominant disorder caused by mutations in the AVP gene. It is characterized by delayed-onset progressive polyuria and eventual AVP neuronal loss. In AVP neurons of FNDI model mice, mutant protein aggregates are confined to a specific compartment of the ER, called the ER-associated compartment (ERAC). The formation of ERACs contributes to maintaining the function of the remaining intact ER, and mutant protein aggregates in ERACs undergo autophagic-lysosomal degradation without isolation or translocation from the ER, representing a novel protein degradation system in the ER.

Anti-tumor effects of anti-programmed cell death-1 antibody treatment are attenuated in streptozotocin-induced diabetic mice.

Hyperglycemia impairs immune response; however, it remains unknown whether the anti-tumor effects of anti-programmed cell death-1 antibody (PD-1-Ab) treatment are changed in hyperglycemic conditions. We analyzed the effect of PD-1-Ab on tumor growth in streptozotocin-induced diabetic mice (STZ-mice) subcutaneously inoculated with MC38 (a colon carcinoma cell line). Furthermore, we assessed the expression of chemokines by polymerase chain reaction (PCR) array in tumor-draining lymph nodes (dLNs) of these mice and MC38 cells cultured in different glucose concentrations. The suppressive effect of PD-1-Ab on tumor growth was attenuated. This was accompanied by fewer tumor-infiltrating CD8+ T cells, and STZ-mice had fewer tumor-infiltrating CD11c+ dendritic cells (DCs) than normoglycemic mice. mRNA expression levels of CXCL9, a chemokine recruiting CD8+ T cells, were lower in dLNs of STZ-mice than in normoglycemic mice after PD-1-Ab treatment, and its protein was expressed in DCs. In MC38 cells cultured with 25 mM glucose, mRNA expression of CCL7, a chemokine recruiting DCs, was decreased compared to cells cultured with 5 mM glucose. These results suggest that the STZ-induced hyperglycemia impairs the effect of PD-1-Ab treatment on MC38 tumor growth, and is accompanied by reduced infiltration of DCs and CD8+ T cells and decreased expression of CCL7 and CXCL9.

The First Identification of a Narnavirus in Bigyra, a Marine Protist.

Current information on the diversity and evolution of eukaryotic RNA viruses is biased towards host lineages, such as animals, plants, and fungi. Although protists represent the majority of eukaryotic diversity, our understanding of the protist RNA virosphere is still limited. To reveal untapped RNA viral diversity, we screened RNA viruses from 30 marine protist isolates and identified a novel RNA virus named Haloplacidia narnavirus 1 (HpNV1). A phylogenetic ana-lysis revealed that HpNV1 is a new member of the family Narnaviridae. The present study filled a gap in the distribution of narnaviruses and implies their wide distribution in Stramenopiles.

Generation of hypothalamic neural stem cell-like cells in vitro from human pluripotent stem cells.

When damaged, restoring the function of the hypothalamus is currently impossible. It is unclear whether neural stem cells exist in the hypothalamus. Studies have reported that adult rodent tanycytes around the third ventricle function as hypothalamic neural stem cell-like cells. However, it is currently impossible to collect periventricular cells from humans. We attempted to generate hypothalamic neural stem cell-like cells from human embryonic stem cells (ESCs). We focused on retina and anterior neural fold homeobox (RAX) because its expression is gradually restricted to tanycytes during the late embryonic stage. We differentiated RAX::VENUS knockin human ESCs (hESCs) into hypothalamic organoids and sorted RAX+ cells from mature organoids. The isolated RAX+ cells formed neurospheres and exhibited self-renewal and multipotency. Neurogenesis was observed when neurospheres were transplanted into the mouse hypothalamus. We isolated RAX+ hypothalamic neural stem cell-like cells from wild-type human ES organoids. This is the first study to differentiate human hypothalamic neural stem cell-like cells from pluripotent stem cells.

Identification of novel RNA mycoviruses from wild mushroom isolates in Japan.

The characterization of viruses from environmental samples could aid in our understanding of their ecological significance and potential for biotechnological exploitation. While there has been much focus on pathogenic fungi or commercially cultivated mushrooms, attention to viruses from wild Basidiomycota mushrooms is lacking. Therefore, in this study, we conducted viral screening of fungal mycelia isolated from wild basidiocarps using agarose gel electrophoresis (AGE) and fragmented and primer-ligated dsRNA sequencing (FLDS). Among the 51 isolates, seven isolates were detected with virus-like bands during the initial screening with AGE, but only five isolates were detected with viruses after long-term storage. Using the FLDS method, we obtained seven viral genome sequences, including five double-stranded RNA (dsRNA) viruses belonging to Partitiviridae and Curvulaviridae, one positive-sense single-stranded RNA (ssRNA) virus belonging to Endornaviridae and one negative-sense ssRNA virus belonging to Tulasviridae (Bunyavirales). All viruses characterized in this study are novel species. These findings greatly expanded our knowledge of the diversity of RNA viruses from environmental samples.

Knockdown of endoplasmic reticulum chaperone BiP leads to the death of parvocellular AVP/CRH neurons in mice.

Arginine vasopressin (AVP) is expressed in both magnocellular (magnAVP) and parvocellular AVP (parvAVP) neurons of the paraventricular nucleus, and AVP colocalizes with corticotropin-releasing hormone (CRH) only in the parvocellular neurons. The immunoglobulin heavy chain binding protein (BiP) is a major endoplasmic reticulum (ER) chaperone which regulates the unfolded protein response under ER stress. We previously demonstrated that knockdown of BiP in magnAVP neurons exacerbated ER stress, which resulted in the autophagy-associated cell death of magnAVP neurons. Using the same approach, in the present study we examined the role of BiP in mouse parvAVP/CRH neurons. Our data demonstrate that BiP is expressed in mouse parvAVP/CRH neurons under nonstress conditions and is upregulated in proportion to the increase in CRH expression after adrenalectomy. For BiP knockdown in parvAVP/CRH neurons, we utilized a viral approach in combination with shRNA interference. Knockdown of BiP expression induced ER stress in parvAVP/CRH neurons, as reflected by the expression of C/EBP homologous protein. Furthermore, BiP knockdown led to the loss of parvAVP/CRH neurons after 4 weeks. In summary, our results demonstrate that BiP plays a pivotal role in parvAVP/CRH neurons, which function as neuroendocrine cells producing a large number of secretory proteins.

Resting energy expenditure depends on energy intake during weight loss in people with obesity: a retrospective cohort study.

Objective: Resting energy expenditure (REE) decreases if there is reduced energy intake and body weight (BW). The decrease in REE could make it difficult for patients with obesity to maintain decreased BW. This study aimed to investigate the correlation among changes in REE, energy intake, and BW during the weight loss process in patients with obesity. Materials and methods: We conducted a retrospective cohort study of patients hospitalized for the treatment of obesity in Japan. Patients received fully controlled diet during hospitalization and performed exercises if able. REE was measured once a week using a hand-held indirect calorimetry. Energy intake was determined by actual dietary intake. Results: Of 44 inpatients with obesity, 17 were included in the analysis. Their BW decreased significantly after 1 week (-4.7 ± 2.0 kg, P < 0.001) and 2 weeks (-5.7 ± 2.2 kg, P < 0.001). The change in REE after 1 and 2 weeks was positively correlated with the energy intake/energy expenditure ratio (r = 0.66, P = 0.004 at 1 week, r = 0.71, P = 0.002 at 2 weeks). Using a regression equation (y = 0.5257x - 43.579), if the energy intake/energy expenditure ratio within the second week was 82.9%, the REE after 2 weeks was similar to the baseline level. There was no significant correlation between the change in REE and BW. Conclusion: Our data suggest that changes in REE depend on energy intake/energy expenditure ratio and that the decrease in REE can be minimized by matching energy intake to energy expenditure, even during the weight loss process.

Mineralocorticoids induce polyuria by reducing apical aquaporin-2 expression of the kidney in partial vasopressin deficiency.

The symptoms of diabetes insipidus may be masked by the concurrence of adrenal insufficiency and emerge after the administration of hydrocortisone, occasionally at high doses. To elucidate the mechanism underlying polyuria induced by the administration of high-dose corticosteroids in the deficiency of arginine vasopressin (AVP), we first examined the secretion of AVP in three patients in whom polyuria was observed only after the administration of high-dose corticosteroids. Next, we examined the effects of dexamethasone or aldosterone on water balance in wild-type and familial neurohypophyseal diabetes insipidus (FNDI) model mice. A hypertonic saline test showed that AVP secretion was partially impaired in all patients. In one patient, there were no apparent changes in AVP secretion before and after the administration of high-dose corticosteroids. In FNDI mice, unlike dexamethasone, the administration of aldosterone increased urine volumes and decreased urine osmolality. Immunohistochemical analyses showed that, after the administration of aldosterone in FNDI mice, aquaporin-2 expression was decreased in the apical membrane and increased in the basolateral membrane in the collecting duct. These changes were not observed in wild-type mice. The present data suggest that treatment with mineralocorticoids induces polyuria by reducing aquaporin-2 expression in the apical membrane of the kidney in partial AVP deficiency.

Resting energy expenditure depends on energy intake during weight loss in people with obesity: a retrospective cohort study

Abstract Objective: Resting energy expenditure (REE) decreases if there is reduced energy intake and body weight (BW). The decrease in REE could make it difficult for patients with obesity to maintain decreased BW. This study aimed to investigate the correlation among changes in REE, energy intake, and BW during the weight loss process in patients with obesity. Materials and methods: We conducted a retrospective cohort study of patients hospitalized for the treatment of obesity in Japan. Patients received fully controlled diet during hospitalization and performed exercises if able. REE was measured once a week using a hand-held indirect calorimetry. Energy intake was determined by actual dietary intake. Results: Of 44 inpatients with obesity, 17 were included in the analysis. Their BW decreased significantly after 1 week (−4.7 ± 2.0 kg, P < 0.001) and 2 weeks (−5.7 ± 2.2 kg, P < 0.001). The change in REE after 1 and 2 weeks was positively correlated with the energy intake/energy expenditure ratio (r = 0.66, P = 0.004 at 1 week, r = 0.71, P = 0.002 at 2 weeks). Using a regression equation (y = 0.5257x - 43.579), if the energy intake/energy expenditure ratio within the second week was 82.9%, the REE after 2 weeks was similar to the baseline level. There was no significant correlation between the change in REE and BW. Conclusions: Our data suggest that changes in REE depend on energy intake/energy expenditure ratio and that the decrease in REE can be minimized by matching energy intake to energy expenditure, even during the weight loss process.