Pelvic Palpatory Tests in Manual Therapy and Osteopathy: A Critical Review of the Literature and Suggestions for New Research.

Manual therapists apply physical interventions to the entire structure of the body to promote healing, prevent pathologies, and improve patient health. In osteopathic practice, palpatory evaluation is considered a fundamental clinical practice requirement for identifying somatic dysfunction. Most of the articles published in this area have failed to demonstrate a level of reproducibility that supports palpation in evidence-based clinical practice. When considering the poor reliability of the palpatory tests highlighted in the literature, a discrepancy is noted with what is known about the tactile sensitivity of human hands. For static touch, the minimum size that can be detected, in the absence of applied movement or vibration, is approximately 0.2 mm. Yet, it seems that this high level of precision is insufficient to ensure reliability in the tests used to evaluate osteopathic somatic dysfunction. The purpose that underscores this article is to determine how these two contradictory elements, high sensitivity and low reliability, can be present in palpatory tests. The article reports the literature findings regarding palpatory tests of pelvic, which is an important structure for clinical purposes. Additionally, a critical review of how these studies were conducted is provided to identify any elements that may justify the obtained results. Following recent accredited guidelines present in the literature, we propose suggestions on vision training methods, manual perception refinement training, the search for anatomical markers, and the position of the examiner in relation to the examinee that may be useful for future studies on the topic covered by the article.

Generation of Human-Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells of C9ORF72-Associated Amyotrophic Lateral Sclerosis Patients.

Disease modeling of neuromuscular disorders, such as amyotrophic lateral sclerosis (ALS), is hindered by limited accessibility of affected cells. This problem can be overcome by generation of human induced pluripotent stem cells (hiPSC), which can be then differentiated into required cells. Here, we describe the detailed protocol of hiPSC establishment from peripheral blood mononuclear cells (PBMC) of two ALS patients with detected expansion of G4C2 (GGGGCC) repeats in the first intron of C9ORF72 gene, known to be linked with the most common form of familial ALS.Successful PBMC reprogramming with non-integrating Sendai vectors was confirmed by expression of pluripotency markers: OCT4, NANOG, SSEA4, and TRA-1-60 in obtained hiPSC and their ability to differentiate into cells of three germ layers.The generated ALS-patient-specific hiPSC create a possibility for deciphering molecular basis of this devastating neuromuscular disease.

Neuropsychological features of somatic symptom disorder and depression/anxiety in Taiwan: An analysis based on the comorbidity status.

Individuals with somatic symptom disorder (SSD) often have comorbid depression or anxiety, but whether SSD is associated with specific neuropsychological functions has yet to be fully examined. We analyzed which neuropsychological features are more closely associated with SSD, anxiety, and depression. In this case-control study, we recruited 140 individuals with SSD, 104 individuals with affective disorders without SSD, and 159 healthy controls in Taiwan. We collected DSM-5 diagnoses, questionnaire scores, and performance on eight tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) for each participant. Several CANTAB tasks involving attention, executive function, and social cognition showed significant group differences. In the adjusted analysis, the tasks significantly associated with SSD were the Match to Sample Visual Search (MTS) and the Emotion Recognition Task (ERT). Among the questionnaires, the Cognitions about Body and Health Questionnaire showed the most significant associations with the tasks, specifically with Rapid Visual Information Processing, MTS, Paired Associates Learning, Spatial Working Memory, Intra-Extra Dimensional Set Shift, and ERT. We conclude that the MTS and ERT tasks show significant relationships with both SSD diagnosis and related questionnaires. These tasks primarily involve selective attention and negative emotion regulation.

Propagation path of a flowering cherry (Cerasus × yedoensis) cultivar 'Somei-Yoshino' traced by somatic mutations.

In the long history of human relations with flowering cherry trees in Japan, 'Somei-Yoshino' occupies an exceptional position among a variety of flowering trees: it is a self-incompatible interspecific hybrid but has been enthusiastically planted by grafting throughout Japan, due most likely to its flamboyant appearance upon full bloom. Thus, 'Somei-Yoshino' gives us a rare opportunity to trace and investigate the occurrence and distribution of somatic mutations within a single plant species through analysis of the genomes of the clonally propagated trees grown under a variety of geographical and artificial environments. In the studies presented here, a total of 46 samples of 'Somei-Yoshino' trees were collected and their genomes were analyzed. We identified 684 single nucleotide mutations, of which 71 were present in more than two samples. Clustering analysis of the mutations indicated that the 46 samples were classified into eight groups, four of which included 36 of the 46 samples analyzed. Interestingly, all the four tree samples collected in Ueno Park of Tokyo were members of the four groups mentioned above. Based on comparative analysis of their mutations, one of the four trees growing in Ueno Park was concluded to be the closest to the original ancestor. We propose that somatic mutations may be used as tracers to establish the ancestral relationship amongst clonally propagated individuals.

Delusion of pregnancy: Case series.

Delusion of pregnancy is a relatively uncommon manifestation in psychotic patients. Differentiating it from closely related clinical entities like pseudocyesis/pseudopregnancy can be a challenge in clinical setting. Diagnosis of a psychotic illness with delusional pregnancy as the presenting feature in the absence of other florid symptoms of psychosis is a different challenge altogether. Currently, there is no consensus on the pharmacotherapy and psychotherapy of delusional pregnancy. We present a case series on delusional pregnancy with the intent to answer some of these gaps in the literature.

An investigation of antioxidative and anti-inflammatory effects of Taraxacum coreanum (white dandelion) in lactating Holstein dairy cows.

Objective: The aim of this investigation was to examine the impact of Taraxacum coreanum (known as dandelion) (TC) and TC mixtures with milk thistle (MT) or Aspergillus oryzae (AO) as feed additives on the immune response, milk quality, and milk production in Holstein cows over 6 weeks of administration. Materials and Methods: Thirty-two healthy Holstein dairy cows were provided 30 kg of total mixed ration (TMR) with no TC, 90 gm TC, 54 gm TC + 36 gm MT, or 54 gm TC + 36 gm AO 40% groups. The feed additives were supplied daily in two equal portions (per 45 gm) by topdressing the TMR for 6 weeks. Milk and blood samples were collected weekly. Results: In the TC-treated cows (TC, TC + MT, and TC + AO groups), significantly lower peripheral blood white blood cell (WBC) counts at 6 weeks and milk somatic cell counts (SCCs) at 4-6 weeks of administration were observed. Concentrations of serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were notably elevated in cows treated with TC for 4-6 weeks, while levels of proinflammatory cytokines concentrations of tumor necrosis factor-alpha (TNF-α) and chemokine (IL-8) were significantly reduced in TC-treated cows after 3-6 weeks of administration. Conclusion: These results suggested that TC or a TC mixture with other medicinal herbs supplementations enhanced the serum antioxidative activities and, consequently, might suppress the adverse immune response due to lower serum TNF-α and IL-8 release supported by lower WBC and SCC counts.

A systematic cognitive behavioral therapy approach for pediatric disorders of gut-brain interaction.

OBJECTIVE: Cognitive Behavioral Therapy (CBT) for youth with Disorders of Gut-Brain Interaction (DGBIs) is effective; however, there are calls in the field to strengthen the evidence base and identify specific mechanisms of treatment that yield the most benefit for this patient population. A unique, systematic treatment approach of CBT with initial evidence for success for pediatric patients with DGBIs was evaluated to further demonstrate its clinical utility in this population. METHODS: This was a retrospective study of 42 pediatric patients aged 11-17 years with DGBIs, who were diagnosed and referred for CBT by pediatric gastroenterology providers. Providers also completed a survey rating acceptability and effectiveness of CBT. The systematic CBT approach included 10 sessions delivered by a psychologist at an integrated Pediatric GI Clinic. RESULTS: Review of 42 pediatric charts showed significant decreases in self-reported functional disability, abdominal pain, as well as depression and anxiety symptoms pre- to post-CBT completion. A moderation effect was observed where patients reporting higher levels of depressive symptoms and primary symptom of abdominal pain reported smaller reductions in functional impairment compared to those with lower levels of depression and primary symptom of nausea or vomiting. Pediatric Gastroenterology providers were satisfied with this psychological treatment approach. CONCLUSIONS: This study provides evidence for acceptability and effectiveness of implementation of a systematic CBT approach for pediatric DGBIs in an integrated GI clinic, as well as areas worthy of future research, including identifying the most important mechanisms of treatment and factors that influence treatment response.

The molecular profile of gastric intraepithelial foveolar type neoplasia based on somatic copy number alterations and multiple mutation analysis.

BACKGROUND: Gastric foveolar type neoplasia is a rare histological variant of gastric tumors. It is very difficult to differentiate between benign and malignant intraepithelial foveolar neoplasia (IFN). Although limited molecular alterations have been identified in IFNs, somatic copy number alterations (SCNAs), which are linked to tumor progression, have not been systematically evaluated in IFN. METHODS: The aim of the present study was to comprehensively examine SCNAs using a SNP array in 37 cases of IFN, compared with intestinal type dysplasia, including 39 low grade (LGD) and 32 high grade dysplasia (HGD) cases. In addition, gene mutations were evaluated using a gene panel. Finally, we attempted to determine molecular profiles using a hierarchical clustering analysis. RESULTS: Two patterns could be categorized according to the SCNAs in 108 tumors examined: high (subgroup 1) and low (subgroup 2) frequencies of SCNAs. Although IFN and LGD were associated with subgroup 2, HGD was found in both subgroups. The median numbers of total SCNAs and copy number gains were higher in IFN or HGD than in LGD. In addition, the IFN genotype was characterized by altered genes located at 4p13-4q35.2, including RAP1GDS1 and LEF1, which may be associated with IFN development. Finally, no significant mutations were found in IFNs using a gene panel. CONCLUSIONS: The current molecular profiles of IFN may help elucidate the mechanisms of IFN development.

Identifying Future Study Designs and Indicators for Somatic Health Associated with Diets of Cohorts Living in Eco-Regions: Findings from the INSUM Expert Workshop.

Diets, but also overall food environments, comprise a variety of significant factors with direct and indirect impacts on human health. Eco-Regions are geographical areas with a territorial approach to rural development, utilizing organic food and farming practices, and principles and promoting sustainable communities and food systems. However, so far, little attention has been given to quantifying aspects of the health of citizens living in these sustainable transition territories. The project "Indicators for Assessment of Health Effects of Consumption of Sustainable, Organic School Meals in Eco-Regions" (INSUM) aims to identify and discuss research approaches and indicators that could be applied to effectively measure the somatic, mental, and social health dimensions of citizens in Eco-Regions, linked to the intake of organic foods in their diets. In this paper, we focus on the somatic (physical) health dimension. A two-day workshop was held to discuss suitable methodology with an interdisciplinary, international group of experts. The results showed the limitations of commonly used tools for measuring dietary intake (e.g., relying on the memory of participants), and nutritional biomarkers (e.g., variations in correlations with specific intakes) for research understanding dietary intake and the health effects of diets. To investigate the complexity of this issue, the most suitable approach seems to be the combination of traditional markers of physical and mental health alongside emerging indicators such as the microbiome, nutrigenomics, metabolomics, or inflammatory biomarkers. Using new, digital, non-invasive, and wearable technologies to monitor indicators could complement future research. We conclude that future studies should adopt systemic, multidisciplinary approaches by combining not only indicators of somatic and mental health and social wellbeing (MHSW) but also considering the potential benefits of organic diets for health as well as aspects of sustainability connected to food environments.

A Novel Affordable and Reliable Framework for Accurate Detection and Comprehensive Analysis of Somatic Mutations in Cancer.

Accurate detection and analysis of somatic variants in cancer involve multiple third-party tools with complex dependencies and configurations, leading to laborious, error-prone, and time-consuming data conversions. This approach lacks accuracy, reproducibility, and portability, limiting clinical application. Musta was developed to address these issues as an end-to-end pipeline for detecting, classifying, and interpreting cancer mutations. Musta is based on a Python command-line tool designed to manage tumor-normal samples for precise somatic mutation analysis. The core is a Snakemake-based workflow that covers all key cancer genomics steps, including variant calling, mutational signature deconvolution, variant annotation, driver gene detection, pathway analysis, and tumor heterogeneity estimation. Musta is easy to install on any system via Docker, with a Makefile handling installation, configuration, and execution, allowing for full or partial pipeline runs. Musta has been validated at the CRS4-NGS Core facility and tested on large datasets from The Cancer Genome Atlas and the Beijing Institute of Genomics. Musta has proven robust and flexible for somatic variant analysis in cancer. It is user-friendly, requiring no specialized programming skills, and enables data processing with a single command line. Its reproducibility ensures consistent results across users following the same protocol.

Saliva-derived DNA is suitable for the detection of clonal haematopoiesis of indeterminate potential.

Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with many adverse health outcomes. However, further research is required to understand the critical genes and pathways relevant to CHIP subtypes, evaluate how CHIP clones evolve with time, and further advance functional characterisation and therapeutic studies. Large epidemiological studies are well placed to address these questions but often collect saliva rather than blood from participants. Paired saliva- and blood-derived DNA samples from 94 study participants were sequenced using a targeted CHIP-gene panel. The ten genes most frequently identified to carry CHIP-associated variants were analysed. Fourteen unique variants associated with CHIP, ten in DNMT3A, two in TP53 and two in TET2, were identified with a variant allele fraction (VAF) between 0.02 and 0.2 and variant depth ≥ 5 reads. Eleven of these CHIP-associated variants were detected in both the blood- and saliva-derived DNA sample. Three variants were detected in blood with a VAF > 0.02 but fell below this threshold in the paired saliva sample (VAF 0.008-0.013). Saliva-derived DNA is suitable for detecting CHIP-associated variants. Saliva can offer a cost-effective biospecimen that could both advance CHIP research and facilitate clinical translation into settings such as risk prediction, precision prevention, and treatment monitoring.

Mitochondrial DNA D-loop SNPs unveil molecular signatures of milk production variation in Murrah buffalo.

BACKGROUND: The Murrah buffalo, pivotal in Asian agriculture, faces challenges in maximizing milk production despite significant breeding efforts. Recognizing its economic importance, this study investigates mtDNA D-loop variations in Murrah buffalo as potential indicators of milk production variability, addressing challenges in maximizing yield despite significant breeding efforts. METHODS AND RESULTS: Analyzing mtDNA D-loop sequences from 50 buffaloes, we categorized them into Low (Group 1), Medium (Group 2), and High ECM (Group 3) groups based on milk yields, fat and protein percentage of a 30-day period data. Somatic cell mtDNA D-loop analysis revealed distinct genetic variations, with significant differences among ECM groups. Group 2 showed higher SNP prevalence, group 3 had more insertions/deletions, and Group 1 exhibited the highest transition frequency. Notably, a consistent "C" deletion at the 714th position occurred in Groups 1 and 3, prevalent in 68% of Group 2. A G-A variation at the 93rd position was specific to the medium ECM group. Negative Tajima D values indicated unique variations in each group, with Group 1 having the highest number, and a specific SNP linked to Group 2 was identified. These SNPs in the D-loop region could impact mtDNA replication, influencing mitochondrial content among animals. Our results provide valuable insights into the role of mtDNA D-loop polymorphisms in milk production traits in Murrah buffalo. CONCLUSIONS: Our research highlights the potential for valuable markers of cellular energy efficiency in Murrah buffalo. Exploring diverse cytoplasmic backgrounds opens avenues for mtDNA-based selection strategies, enhancing milk production and optimizing genetic traits for the dairy industry.

Kappa-opioid receptor antagonism in the nucleus accumbens shell distinguishes escalated alcohol consumption and negative affective-like behavior from physiological withdrawal in alcohol-dependence.

Alcohol use disorder (AUD) is a chronic relapsing disease that is deleterious at individual, familial, and societal levels. Although AUD is one of the highest preventable causes of death in the USA, therapies for the treatment of AUD are not sufficient given the heterogeneity of the disorder and the limited number of approved medications. To provide better pharmacological strategies, it is important to understand the neurological underpinnings of AUD. Evidence implicates the endogenous dynorphin (DYN)/κ-opioid receptor (KOR) system recruitment in dysphoric and negative emotional states in AUD to promote maladaptive behavioral regulation. The nucleus accumbens shell (AcbSh), mediating motivational and emotional processes that is a component of the mesolimbic dopamine system and the extended amygdala, is an important site related to alcohol's reinforcing actions (both positive and negative) and neuroadaptations in the AcbSh DYN/KOR system have been documented to induce maladaptive symptoms in AUD. We have previously shown that in other nodes of the extended amygdala, site-specific KOR antagonism can distinguish different symptoms of alcohol dependence and withdrawal. In the current study, we examined the role of the KOR signaling in the AcbSh of male Wistar rats in operant alcohol self-administration, measures of negative affective-like behavior, and physiological symptoms during acute alcohol withdrawal in alcohol-dependence. To induce alcohol dependence, rats were exposed to chronic intermittent ethanol vapor for 14 h/day for three months, during which stable escalation of alcohol self-administration was achieved and pharmacological AcbSh KOR antagonism ensued. The results showed that AcbSh KOR antagonism significantly reduced escalated alcohol intake and negative affective-like states but did not alter somatic symptoms of withdrawal. Understanding the relative contribution of these different drivers is important to understand and inform therapeutic efficacy approaches in alcohol dependence and further emphasis the importance of the KOR/DYN system as a target for AUD therapeutics.

Validation of the Persistent Somatic Symptom Stigma scale for Healthcare Professionals (PSSS-HCP).

OBJECTIVE: Persistent somatic symptoms (PSS) describe recurrent or continuously occurring symptoms such as fatigue, dizziness, or pain that have persisted for at least several months. These include single symptoms such as chronic pain, combinations of symptoms, or functional disorders such as fibromyalgia or irritable bowel syndrome. While many studies have explored stigmatisation by healthcare professionals towards people with PSS, there is a lack of validated measurement instruments. We recently developed a stigma scale, the Persistent Somatic Symptom Stigma scale for Healthcare Professionals (PSSS-HCP). The aim of this study is to evaluate the measurement properties (validity and reliability) and factor structure of the PSSS-HCP. STUDY DESIGN AND SETTING: The PSSS-HCP was tested with 121 healthcare professionals across the United Kingdom to evaluate its measurement properties. Analysis of the factor structure was conducted using principal component analysis. We calculated Cronbach's alpha to determine the internal consistency of each (sub)scale. Test re-test reliability was conducted with a sub-sample of participants with a two-week interval. We evaluated convergent validity by testing the association between the PSSS-HCP and the Medical Condition Regard Scale (MCRS) and the influence of social desirability using the short form of the Marlowe Crowne Social Desirability Scale (MCSDS). RESULTS: The PSSS-HCP showed sufficient internal consistency (Cronbach's alpha = 0.84) and sufficient test-retest reliability, intraclass correlation = 0.97 (95% CI 0.94 to 0.99, p<0.001). Convergent validity was sufficient between the PSSS-HCP and the MCRS, and no relationship was found between the PSSS-HCP and the MCSDS. A three factor structure was identified (othering, uneasiness in interaction, non-disclosure) which accounted for 60.5% of the variance using 13 of the 19 tested items. CONCLUSION: The PSSS-HCP can be used to measure PSS stigmatisation by healthcare professionals. The PSSS-HCP has demonstrated sufficient internal consistency, test-retest reliability, convergent validity and minimal influence of social desirability bias. The PSSS-HCP has demonstrated potential to measure important aspects of stigma and provide a foundation for stigma reduction intervention evaluation.

The Influence of Selected Environmental Factors on the Number of Somatic Cells in Cistern and Alveolar Milk of Polish Holstein-Friesian Cows.

The aim of the study was to evaluate the influence of the milking phase on somatic cell count (SCC) in milk obtained from the cisternal and alveolar parts of udders of selected Polish Holstein-Friesian cows. The study also assessed the impact of other genetic and environmental factors on SCC variability in cisternal and alveolar milk, including: the individual cow, lactation stage, age of cow, production level, milking speed, fat-to-protein ratio, and milking type. The research included 15 cows of Polish Holstein-Friesian breed at different ages, lactation stages, and with varying daily milk yield. A total of 210 milk observations were conducted, including 105 for 1 min milking and 105 for 8 min milking. The results obtained in the study indicated that milk obtained during two different milking phases exhibited similar SCC levels (F for LOGSCC = 0.79). The average actual SCC in milk produced by 15 cows in 105 observations for 1 min milking was 219,000 cells/mL, while for 8 min milking it was 229,000 cells/mL. The results were inconclusive, suggesting that SCC in cisternal and alveolar milk must be influenced by factors other than the milking phase. The analysis of variance conducted for this purpose provided the basis for stating a highly statistically significant effect of the individual cow (F for LOGSCC = 147.9), lactation stage (F for LOGSCC = 54.64), age of cow (F for LOGSCC = 12.39), daily production level (F for LOGSCC = 34.49), milking speed (F for LOGSCC = 17.56), and fat-to-protein ratio (F for LOGSCC = 22.99) on the variability of characteristics defining SCC in milk. In summary, SCC is characterized by high variability, influenced by a range of environmental and genetic factors such as the individual cow, lactation stage, age of cow, milking speed, and dietary fat-to-protein ratio. The influence of milking phase (1 min or 8 min) and milking type (morning or evening) should be considered inconclusive based on the entire population studied. For half of the cows, SCC in cisternal milk was higher than in alveolar milk, while for the other half, the situation was reversed. Further observations are required to confirm the hypothesis regarding the extent to which cows' immunological response to bacterial infections is concentrated in the cisternal or alveolar part of the udder under national environmental conditions.

Chimerism and mosaicism shape our physical constitution and impact medical conditions.

ABO blood group discrepancies in healthy individuals were caused by body-wide chimerism and mosaicism. They can be evaluated with new diagnostic options for disease-related cell clones that are typically associated with mosaicism. The observations raise the attention for sporadic mixed-field observations of any blood group antigen. Commentary on: Dauber et al. Body-wide chimerism and mosaicism are predominant causes of naturally occurring ABO discrepancies. Br J Haematol 2024 (Online ahead of print). doi:10.1111/bjh.19618.

Genetic diversification of allohexaploid Brassica hybrids (AABBCC) using a fertile octoploid with excessive C genome set (AABBCCCC).

MAIN CONCLUSION: Using octoploid somatic hybrids with excessive C genome sets, AABBCCCC, a diverse allohexaploid, AABBCC, was produced by C genome reduction through subsequent crossing with various AABB cultivars. Even when somatic hybrids are produced, the plants that are produced are rarely in themselves an innovative crop. In this study, we used somatic hybrids of Brassica juncea (AABB) and B. oleracea (CC) as model cases for the genetic diversification of the somatic hybrids. One cell of 'Akaoba Takana' (B. juncea) and two cells of 'Snow Crown' (B. oleracea) were fused to create several somatic hybrids with excessive C genomes, AABBCCCC. Using AABBCCCC somatic hybrids as mother plants and crossing with 'Akaoba Takana', the AABBCC progenies were generated. When these AABBCC plants were self-fertilized, and flow cytometric (FCM) analysis was performed on the next generations, differences in the relative amount of genome size variation were observed, depending on the different AABBCCCC parents used for AABBCC creation. Further self-progeny was obtained for AABBCC plants with a theoretical allohexaploid DNA index by FCM. However, as the DNA indices of the progeny populations varied between plants used and aneuploid individuals still occurred in the progeny populations, it was difficult to say that the allohexaploid genome was fully stabilized. Next, to obtain genetic diversification of the allohexaploid, different cultivars of B. juncea were crossed with AABBCCCC, resulting in diverse AABBCC plants. Genetic diversity can be further expanded by crossbreeding plants with different AABBCC genome sets. Although genetic stability is necessary to ensure in the later generations, the results obtained in this study show that the use of somatic hybrids with excess genomes is an effective strategy for creating innovative crops.