Digital health-based exposure therapies for patients with posttraumatic stress disorder: A systematic review of randomized controlled trials.

Although exposure therapies have established effects in treating posttraumatic stress disorder (PTSD), these therapies might be hindered by issues of cost, distance, time, and human resources, which are potentially alleviated by digital health. Despite the potential of digital health, there is currently no systematic review specifically evaluating digital health-based exposure therapies. We aimed to conduct a systematic literature review of randomized controlled trials (RCTs) examining the impact of digital health-based exposure therapies in treating patients with PTSD. A literature search was conducted from December 31, 2023, to February 22, 2024, using the PubMed, Web of Science, and PsycINFO databases. A total of 12 RCTs with 1,361 participants were included in the systematic review. These RCTs were conducted mainly in the United States and primarily enrolled military samples. Overall, the utility of digital health-based exposure therapies appeared plausible and comparable to that of in-person therapies. The dropout rate was counterintuitively high, potentially due to technological issues and the absence of personal connections. The findings suggest that digital health-based exposure therapies may potentially resolve the issues of cost, distance, time, and human resources in the treatment of patients with PTSD. Future RCTs should employ larger sample sizes. Addressing technological challenges and the absence of personal connection may be important in resolving the high dropout rate.

Associated factors for multidimensional attitudes and behaviors of reproductive health toward pregnancy among early and late adolescents in Tanzania: a cross-sectional study.

BACKGROUND: Adolescent pregnancy is a serious reproductive health problem in Tanzania. However, the risk factors for multidimensional attitudes and behaviors of reproductive health toward pregnancy in Tanzanian adolescents remain unexplored. METHODS: We collected baseline characteristics and information on attitudes and behaviors of reproductive health from 4161 Tanzanian adolescents in all 54 primary and secondary schools in the Korogwe district. We applied mixed effect multiple regression analyses stratified by sex to find the factors related to reproductive health attitudes and behaviors toward pregnancy. RESULTS: In female students, regarding the attitudes of reproductive health, higher age, hope for marriage in the future, a talk with a parent about sex or pregnancy, and a higher hope score were significantly associated with a lower score. For the behaviors of reproductive health, higher age, a talk with a parent about sex or pregnancy, time to talk with a parent about daily life, and a higher hope score were significantly associated with a lower score. In male students, regarding the attitudes of reproductive health, a higher hope score was significantly associated with a lower score. For the behaviors of reproductive health, higher age, time to talk with a parent about daily life, and a higher hope score was significantly associated with a lower score. CONCLUSIONS: The heterogeneous factor-outcomes association between female and male students suggested that sex-specialized interventions may be required to change their risky attitudes or behaviors of reproductive health. Although we cannot conclude as points of intervention, our study suggested that it may be practical to improve parent-adolescents communication about sex or reproductive health and change adolescents' views of pregnancy or marriage for gaining financial or social status.

An Evaluation of the Protein Requirements of Japanese Young Men by Consuming Two Types of Dairy Proteins Using the Indicator Amino Acid Oxidation Method.

The indicator amino acid oxidation method is a relatively new method for determining protein requirements. Our hypothesis was that the protein requirement of the casein-whey protein mixture (70% casein and 30% whey protein) was lower than the protein requirement of plain casein, because casein and whey proteins compensate for the lack of the first-limiting amino acids. The optimal mixing ratio was determined based on the amino acid scoring pattern which is used to calculate the digestible indispensable amino acid score. In this study, digestibility was not considered to determine the optimal mixing ratio because dairy protein is a good source of digestible protein. This study aimed to evaluate the protein requirements of Japanese young men by consuming casein and casein-whey protein mixture. Ten healthy young men (22±0.2 y old) participated in 12 experiments according to a graded protein intake (0.5, 0.7, 0.9, 1.0, 1.2, 1.4 g/kg/d) of casein and casein-whey protein mixture. The mean protein requirement was calculated as the breakpoint of breath 13CO2 enrichment using change-point regression models. The mean protein requirements of Japanese young men by consuming casein and casein-whey protein mixture were estimated to be 1.00 g/kg/d and 0.90 g/kg/d, respectively. These estimated requirements were consistent with the protein quality expected from the amount of the first-limiting amino acids. The indicator amino acid oxidation method may be useful to evaluate protein quality.

Anti-inflammatory and nutritional improvement effects of dietary supplementation combined with fish oil in patients with epithelial cancer.

The present study investigated the effects of dietary supplementation combined with fish oil containing relatively low levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the inflammatory and nutritional status of patients with epithelial cancer. Fish oil capsules (498 mg EPA and 213 mg DHA) and dietary supplements (100 kcal and 5 g protein) were administered for 8 weeks to 20 patients with cancer and inflammation [C-reactive protein (CRP) ≥0.30 mg/dl]. Blood EPA levels increased significantly after 4 and 8 weeks, while no significant differences were observed in log-transformed (log) CRP levels, which were the major inflammatory indices in these patients. A declining trend was observed at 8 weeks after excluding 2 patients with suspected infection (P=0.06). A significant increase was observed from week 0 to week 8 for log interleukin-6 (IL-6) levels. After excluding the 2 patients with suspected infection, no significant difference was observed when comparing week 0 to week 8 for log IL-6. No deterioration in albumin or pre-albumin levels was observed. These results suggest that although suppression of acute inflammation associated with infection is difficult, intake of relatively low EPA and DHA supplements may be effective for mild chronic inflammation in patients with epithelial cancer without infection. Large-scale randomized clinical trials are required to make the final decision regarding efficacy. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; 06/07/2018, UMIN000033309).

A live imaging system to analyze spatiotemporal dynamics of RNA polymerase II modification in Arabidopsis thaliana.

Spatiotemporal changes in general transcription levels play a vital role in the dynamic regulation of various critical activities. Phosphorylation levels at Ser2 in heptad repeats within the C-terminal domain of RNA polymerase II, representing the elongation form, is an indicator of transcription. However, rapid transcriptional changes during tissue development and cellular phenomena are difficult to capture in living organisms. We introduced a genetically encoded system termed modification-specific intracellular antibody (mintbody) into Arabidopsis thaliana. We developed a protein processing- and 2A peptide-mediated two-component system for real-time quantitative measurement of endogenous modification level. This system enables quantitative tracking of the spatiotemporal dynamics of transcription. Using this method, we observed that the transcription level varies among tissues in the root and changes dynamically during the mitotic phase. The approach is effective for achieving live visualization of the transcription level in a single cell and facilitates an improved understanding of spatiotemporal transcription dynamics.

Evaluation of Protein Requirements Using the Indicator Amino Acid Oxidation Method.

The indicator amino acid oxidation (IAAO) method is a novel method for determining protein requirements. Recently, the protein requirement of healthy young men was reevaluated using this method, and the currently recommended protein requirement based on nitrogen balance study was found to be deficient. Similarly, with respect to experimental animals, the protein concentration used widely in the experimental diets was assumed to be deficient. However, only a few studies have tested the IAAO method in experimental animals. In particular, there are no studies on the protein requirement of adult rats measured using this method. Therefore, we applied the IAAO method to adult rats, to determine their casein protein requirement. Male Wistar/ST rats (15-18 wk old, housed in lighting (lights on from 23:00 to 11:00) conditions) were provided with the test diet including graded casein (5, 7, 9, 13, 17, 21 and 25%) every 2 h from 11:00 to 17:00. Tracer administration of 13C-phenylalanine was performed hourly from 14:00 to 17:00. Breath 13CO2 was measured every 30 min after the first tracer administration. There were significant differences between the 13CO2 concentration of the 5% and 17% casein groups at 17:00 and 18:00 (p<0.05). The mean casein protein requirement and recommended dietary allowance (RDA) were estimated to be 5.2 g/kg BW/d and 7.0 g/kg BW/d using the mixed-effect change point regression model, respectively. Our results indicated that the recommended casein value may be slightly deficient to satisfy the protein metabolic demand of some adult rats.

Epicutaneous immunogenicity of partially hydrolyzed whey protein evaluated using tape-stripped mouse model.

BACKGROUND: Hydrolyzed cow's milk protein formulas are widely used for infants with a history or risk of cow's milk allergy. Based on the current theory that food allergen sensitization occurs via the skin, we investigated the epicutaneous immunogenicity of partially hydrolyzed whey proteins, which are ingredients in infant formulas. METHODS: BALB/c mice were exposed epicutaneously to whey protein concentrate (WPC) or partial whey protein hydrolysates (PWH1 or PWH2) on tape-stripped skin. Sensitization was assessed by evaluating serum ß-lactoglobulin (ß-LG)-specific antibodies, basophil activation, and cytokine production from ß-LG-stimulated lymphoid cells. The anaphylaxis reaction was evaluated by measuring the rectal temperature and plasma level of mouse mast cell protease-1 after oral ß-LG challenge. Immune cell accumulation in the skin was also analyzed. RESULTS: Substantive sensitization and ß-LG-induced anaphylaxis reaction were observed in WPC-exposed mice, whereas no significant changes were observed in PWH1- or PWH2-exposed mice. The basophil and eosinophil counts increased in WPC-exposed murine skin, not but in PWH1- or PWH2-exposed mice. CONCLUSION: The epicutaneous immunogenicity of PWH1 and PWH2 is markedly decreased, which may reduce the risk of allergen sensitization. Further studies are required to investigate the clinical value of these partial hydrolysates for high-risk infants.

Ingestion of Casein Hydrolysate Induces Oral Tolerance and Suppresses Subsequent Epicutaneous Sensitization and Development of Anaphylaxis Reaction to Casein in Mice.

BACKGROUND: Casein is the most dominant causal allergen in cow's milk allergy (CMA). Casein hydrolysates are frequently applied in infant formulas for children with a risk or history of CMA. However, there is limited information on the oral tolerance-inducing ability of casein hydrolysates. OBJECTIVES: The aim of this study was to investigate whether the ingestion of casein hydrolysate induces tolerance to casein, ultimately preventing subsequent epicutaneous sensitization and development of an anaphylaxis reaction. METHODS: BALB/c mice were orally administered casein or a casein hydrolysate (CNH) via the drinking water and were then epicutaneously sensitized by repeated exposure of casein on tape-stripped skin. Sensitization was assessed by basophil activation tests, the serum levels of casein-specific antibodies, and cytokine production from casein-stimulated spleen and mesenteric lymph node (MLN) cells. Occurrence of an anaphylaxis reaction was evaluated by measuring rectal temperature and the plasma level of mouse mast cell protease-1 (mMCP-1) after oral casein challenges. The T cell population in the spleen and MLN was assessed by flow cytometry. Intestinal mast cells and basophils were analyzed histologically. RESULTS: Sensitization and anaphylaxis reaction to casein were significantly suppressed in casein- or CNH-fed mice compared to controls. Prior ingestion of casein or CNH had no effect on the population of regulatory T cells and activated T cells in lymphoid tissues. Intestinal basophils increased by the epicutaneous sensitization of casein, which was suppressed in casein- or CNH-fed mice. Although the increase in the plasma level of mMCP-1 after oral challenge was suppressed in casein- or CNH-fed mice, there was no change in the number of intestinal mast cells. CONCLUSION: Prior ingestion of casein or CNH induced oral tolerance and suppressed subsequent epicutaneous sensitization and development of systemic anaphylaxis to casein.

Wounding stress induces phenylalanine ammonia lyases, leading to the accumulation of phenylpropanoids in the model liverwort Marchantia polymorpha.

Wounding stress induces the biosynthesis of various specialized metabolites in plants. In this study, wounding induced the biosynthesis of luteolin, apigenin, and isoriccardin C, which are biosynthesized through the phenylpropanoid pathway, in the model liverwort Marchantia polymorpha L (Marchantiaceae). Recombinant M. polymorpha phenylalanine ammonia lyases (MpPALs) exhibited PAL activity in vitro and converted phenylalanine into trans-cinnamic acid. Based on semi-quantitative RT-PCR analysis, the expression levels of the MpPAL genes were up-regulated after wounding. α-Aminooxy-ß-phenylpropionic acid, a PAL inhibitor, suppressed the production of wounding-induced phenolic compounds, luteolin, apigenin, and isoriccardin C, in M. polymorpha. Thus, PAL is a committed step in the biosynthesis of phenylpropanoids in response to wounding in M. polymorpha. This study suggests that wound-induced specialized metabolites such as phenylpropanoids comprise a conserved defense system in land plants.

The initial uridine of primary piRNAs does not create the tenth adenine that Is the hallmark of secondary piRNAs.

PIWI-interacting RNAs (piRNAs) silence transposons in animal germ cells. PIWI proteins bind and amplify piRNAs via the "Ping-Pong" pathway. Because PIWI proteins cleave RNAs between target nucleotides t10 and t11-the nucleotides paired to piRNA guide positions g10 and g11-the first ten nucleotides of piRNAs participating in the Ping-Pong amplification cycle are complementary. Drosophila piRNAs bound to the PIWI protein Aubergine typically begin with uridine (1U), while piRNAs bound to Argonaute3, which are produced by Ping-Pong amplification, often have adenine at position 10 (10A). The Ping-Pong model proposes that the 10A is a consequence of 1U. We find that 10A is not caused by 1U. Instead, fly Aubergine as well as its homologs, Siwi in silkmoth and MILI in mice, have an intrinsic preference for adenine at the t1 position of their target RNAs; during Ping-Pong amplification, this t1A subsequently becomes the g10A of a piRNA bound to Argonaute3.

Clinical and genetic analysis of microtia in Japan.

Microtia is thought to have a multifactorial inheritance, but several investigators disagree. Here we report our survey of the hereditary factors and possible causes. We conducted a questionnaire survey of 428 patients with microtia who were being treated at two hospitals from September 2006 to September 2008. We recorded their age, sex, affected side, duration of gestation, birth weight, age of parents at patients' birth, accompanying malformations, number of siblings, familial occurrence, smoking habit of parents, and medication/disorders of mother during pregnancy, and analysed the results. There were preponderances of male (61%), unilateral (90%) and right-sided disease (59%). Other than the first and second branchial arch syndrome, microtia is often accompanied by other congenital deformities, in particular congenital heart disease; cleft lip, or palate, or both; vertebral defects; and anomalies of extremities. The occurrence in first-degree relatives was 2%. Most maternal disorders and medication taken during pregnancy were common and there was no clear link. Statistically, there was a tendency to low birth weight and high maternal age, but it is not possible to identify these as a specific cause of microtia. Multifactorial inheritance is unlikely to be the cause of microtia as there was only one finding in agreement with its widely accepted characteristics. However, we cannot completely discount it as there were too few cases in some groups to make a judgement.

A role for transcription from a piRNA cluster in de novo piRNA production.

PIWI-interacting RNAs (piRNAs) are at the heart of the nucleic acid-based adaptive immune system against transposons in animal gonads. To date, how the piRNA pathway senses an element as a substrate and how de novo piRNA production is initiated remain elusive. Here, by utilizing a GFP transgene, we screened and obtained clonal silkworm BmN4 cell lines producing massively amplified GFP-derived piRNAs capable of silencing GFP in trans. In multiple independent cell lines where GFP expression was silenced by the piRNA pathway, we detected a common transcript from an endogenous piRNA cluster, in which a part of the cluster is uniquely fused with an antisense GFP sequence. Bioinformatic analyses suggest that the fusion transcript is a source of GFP primary piRNAs. Our data implicate a role for transcription from a piRNA cluster in initiating de novo piRNA production against a new insertion.

A screening method tuned for mRNA processing factors in human cells by evaluation of the luciferase reporter activity and the subcellular distribution of bulk poly(A)+ RNA.

Screening of mRNA export factors in Saccharomyces cerevisiae and Drosophila melanogaster has identified a number of mRNA processing factors involved in multiple mRNA processing steps. However, only limited information is available on human cells. Here we established a screening system searching for mRNA processing factors in human cells by combining the luciferase reporter system and fluorescence in situ hybridization, which evaluates the nuclear/cytoplasmic distribution of bulk poly(A)+ RNA. This system makes it possible to search for the compounds affecting mRNA processing from the various resources.