Mutations in protocadherin 19 (PCDH19), which is on the X-chromosome, cause the brain disease Epilepsy in Females with Mental Retardation (EFMR). EFMR is also often associated with autism-like symptoms. In mice and humans, epilepsy occurs only in heterozygous females who have a mixture of PCDH19 wild-type (WT) and mutant cells caused by random X-inactivation; it does not occur in hemizygous PCDH19 mutant males. This unique inheritance pattern strongly suggests the underlying disease mechanism operates via interference between WT and mutant cells rather than being a result of complete loss of PCDH19 functions. Although it remains unclear whether the other symptoms of EFMR also conform to this unique genotype-phenotype relationship, PCDH19 mutant males were recently reported to demonstrate autism-like symptoms. We, therefore, used a Pcdh19 knockout (KO) mouse model to ask whether a complete lack of PCDH19 causes autism-like behaviors. Consistent with the autism observed in EFMR females, we found Pcdh19 heterozygous KO female mice (with mosaic expression of PCDH19) show defects in sociability in the 3-chamber test. Surprisingly, hemizygous Pcdh19 KO male mice (without any PCDH19 expression) exhibit impaired sociability in the 3-chamber test and reduced social interactions in the reciprocal social interaction test. We also observed that, compared to WT mice, mutant mice display more repetitive behaviors, including self-grooming and rearing. These findings indicate that hemizygous Pcdh19 KO male mice show autism-like phenotypes.

Breast cancer surgery significantly affects the shoulder’s range of motion (ROM) and strength. However, the extent of shoulder impairment, as well as patterns of recovery immediately after surgery, is not fully understood. Therefore, we aimed to investigate shoulder ROM and strength during the early recovery phase after surgery. Thirty-two breast cancer patients were observed five times: the day before surgery, discharge day (postoperative day 1 (POD1) or (POD2)), first outpatient visit (POD7–10), second outpatient visit (POD14–20), and third outpatient visit (POD21–30). We assessed shoulder passive ROM and strength for both affected and unaffected arms at each observation. ROM decreased in both affected and unaffected sides post-surgery. ROM on the affected side did not recover to the pre-surgery level until the third outpatient visit (POD24). In contrast, the ROM on the unaffected side recovered to the pre-surgery level by the first outpatient visit (POD10). The shoulder strength of both arms declined and did not recover to pre-surgery levels. Shoulder strength in the affected arm significantly decreased immediately after surgery (52.9% of the pre-surgery levels) and did not recover until the third outpatient visit (62.5% of the pre-surgery levels), whereas that in the unaffected arm decreased gradually (83.1 ± 2.3 at POD 1 and 78.9 ± 2.9 at POD 24). Descriptively, patterns of recovery in ROM may vary according to types of surgery while patterns of recovery in shoulder strength did not: shoulder strength significantly decreased and did not recover notably regardless of types of surgery. Both shoulder ROM and strength reduced during the early recovery phase after breast cancer surgery regardless of types of surgery, although the degree of reduction was greater in shoulder strength than ROM. Our findings suggest that rehabilitation exercises should be implemented in both upper limbs.

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Background Patients with breast cancer undergo various treatments according to their tumor subtype and cancer stages within 1 year after being diagnosed. Each treatment may cause treatment-related symptoms that have negative impacts on patients’ health and quality of life (QoL) The symptoms can be mitigated when exercise interventions are appropriately applied to patients’ physical and mental conditions. Although many exercise programs were developed and implemented during this period, the effects of tailored exercise programs according to symptoms and cancer trajectories on patients’ long-term health outcomes have not yet been fully elucidated. Therefore, this randomized controlled trial (RCT) aims to investigate the effect of tailored home-based exercise programs on short-term and long-term physiological outcomes in patients with breast cancer. Methods This 12-month RCT includes 96 patients with (stages 1–3) breast cancer randomly assigned to the exercise or control groups. Participants in the exercise group will receive an exercise program tailored to their phase of treatment, type of surgery, and physical function. During post-operative recovery, exercise interventions will be emphasized to improve shoulder range of motion (ROM) and strength. During chemoradiation therapy, exercise intervention will focus on improving physical function and preventing loss of muscle mass. Once chemoradiation therapy is completed, exercise intervention will focus on improving cardiopulmonary fitness and insulin resistance. All interventions will be home-based exercise programs supplemented with once-monthly exercise education and counseling sessions. The main outcome of the study is fasting insulin level at baseline, 6 months, and 1 year post-intervention. Our secondary outcomes include shoulder ROM and strength at 1 month and 3 months, body composition, inflammatory markers, microbiome, QoL, and physical activity levels at 1 month, 6 months, and 1 year post-intervention. Conclusion This trial is the first tailored home-based exercise oncology trial to better understand the comprehensive phase-dependent short- and long-term effects of exercise on shoulder function, body composition, fasting insulin, biomarkers, and microbiome. The results of this study will inform the development of effective exercise programs tailored to the needs of patients with breast cancer post-operatively. Trial registration The protocol for this study is registered with the Korean Clinical Trials Registry (KCT0007853).