Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics.

Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD). KATNAL2, a member of Katanin family microtubule-severing ATPases, is a known ASD risk gene, but its roles in human brain development remain unclear. Here, we show that nonsense truncation of Katnal2 (Katnal2Δ17) in mice results in classic ciliopathy phenotypes, including impaired spermatogenesis and cerebral ventriculomegaly. In both humans and mice, KATNAL2 is highly expressed in ciliated radial glia of the fetal ventricular-subventricular zone as well as in their postnatal ependymal and neuronal progeny. The ventriculomegaly observed in Katnal2Δ17 mice is associated with disrupted primary cilia and ependymal planar cell polarity that results in impaired cilia-generated CSF flow. Further, prefrontal pyramidal neurons in ventriculomegalic Katnal2Δ17 mice exhibit decreased excitatory drive and reduced high-frequency firing. Consistent with these findings in mice, we identified rare, damaging heterozygous germline variants in KATNAL2 in five unrelated patients with neurosurgically treated CH and comorbid ASD or other neurodevelopmental disorders. Mice engineered with the orthologous ASD-associated KATNAL2 F244L missense variant recapitulated the ventriculomegaly found in human patients. Together, these data suggest KATNAL2 pathogenic variants alter intraventricular CSF homeostasis and parenchymal neuronal connectivity by disrupting microtubule dynamics in fetal radial glia and their postnatal ependymal and neuronal descendants. The results identify a molecular mechanism underlying the development of ventriculomegaly in a genetic subset of patients with ASD and may explain persistence of neurodevelopmental phenotypes in some patients with CH despite neurosurgical CSF shunting.

Default mode network electrophysiological dynamics and causal role in creative thinking.

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally-directed cognition. The present study employs stereo-electroencephalography in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by a stronger increase in gamma band power (30-70 Hz) coupled with lower theta band power (4-8 Hz). The difference in activity between the two networks was especially strong during the mind wandering task. Within the DMN, we found that the tasks showed different dynamics, with the alternate uses task engaging the DMN more during the initial stage of the task, and mind wandering in the later stage. Gamma power changes were mainly driven by lateral DMN sites, while theta power displayed task-specific effects. During alternate uses task, theta changes did not show spatial differences within the DMN, while mind wandering was associated to an early lateral and late dorsomedial DMN engagement. Furthermore, causal manipulations of DMN regions using direct cortical stimulation preferentially decreased the originality of responses in the alternative uses task, without affecting fluency or mind wandering. Our results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in divergent thinking. These findings shed light on the neural constructs supporting different forms of cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts.

Biomechanical Analysis of Headless Compression Screw Versus Tension Band Wiring for Proximal Interphalangeal Joint Arthrodesis.

PURPOSE: Proximal interphalangeal (PIP) joint arthrodesis is a procedure employed to address arthritis, instability, and deformity. Multiple fixation methods are available to maintain stability across the arthrodesis interval, including headless compression screws (HCSs), tension band wiring (TBW), plating, and Kirschner wire constructs. The purpose of this study was to compare the biomechanical properties of the HCS and TBW techniques. METHODS: Thirty-two nonthumb digits from the paired upper limbs of four fresh frozen cadavers were divided into pairs, matching contralateral digits from the same specimen. One PIP joint of each pair was fused with an antegrade 3.5 mm HCS, and the second was fused with TBW using 0.035 in. Kirschner wires with 24-gauge dental wire. Each construct was then stressed to 10 N in the radial deviation, ulnar deviation, flexion, and extension planes, and stiffness (N/mm) was calculated. The fingers were stressed to failure in extension with the ultimate load and mode of failure recorded. RESULTS: When stressed in extension, the HCS construct had a significantly greater mean stiffness than the TBW construct (16.4 N/mm vs 10.8 N/mm). The stiffness in all other planes of motion were similar between the two constructs. The mean ultimate load to failure in extension was 91.4 N for the HCS and 41.9 N for the TBW. The most common mode of failure was fracture of the dorsal lip of the proximal phalanx (13/16) for the HCS and bending of the K-wires (15/16) for TBW. CONCLUSIONS: Arthrodesis of the PIP joint using a HCS resulted in a construct that was significantly stiffer in extension with greater than double the load to failure compared to TBW. CLINICAL RELEVANCE: Although the stiffness required to achieve successful PIP joint arthrodesis has not been well quantified, the HCS proved to be the most favorable construct with respect to initial strength and stability.

Fractional Lengthening of Forearm Flexor Tendons: A Cadaveric Biomechanical Analysis.

PURPOSE: Multiple procedures have been described for wrist and finger flexion contractures and spasticity. Fractional lengthening of forearm flexor tendons involves making parallel transverse tenotomies at the musculotendinous junction to elongate the muscle. Currently, there is limited literature to define the biomechanical consequences of this lengthening technique. METHODS: Forty-eight flexor tendons were harvested from eight paired upper limbs including flexor carpi radialis, flexor carpi ulnaris, flexor pollicis longus, and flexor digitorum superficialis tendons. Each tendon that was lengthened was paired with the contralateral tendon as a control. A pair of transverse tenotomies were completed for the fractional lengthening. The first tenotomy was performed at the musculotendinous junction where the tendon narrowed to 75% of its maximal width. The second tenotomy was made 1 cm distal to the first. Tendon length was measured before and after fractional lengthening at a constant resting tension of 1 N. The maximum load at failure of each tendon and the mechanism of failure were each measured and compared with the contralateral side. RESULTS: After fractional lengthening, the mean increase in resting tendon length was 4 mm. When loaded to failure, the mean maximum load of fractionally lengthened tendons was 42% of the mean maximum load of intact tendons. All lengthened tendons failed at the distal tenotomy site. CONCLUSIONS: Fractional lengthening resulted in an increase of 3-6 mm (mean: 4 mm) in tendon length at resting tension. There was a significant loss in tensile strength and load to failure following fractional lengthening compared with an intact musculotendinous unit. CLINICAL RELEVANCE: The reduction in tensile strength following fractional lengthening results in loads at failure that are, in some cases, lower than the estimated forces required to perform basic tasks. Caution during the healing and rehabilitation period is warranted.

Repeat Exchange Autologous Cranioplasty for Recurrent Benign Osteoma: Meta-analysis and Literature Review.

Osteomas are benign bony lesions that can occur throughout the craniofacial skeleton. Surgical excision can be an effective treatment, as recurrence is relatively uncommon. Outside of incomplete resection, causes of recurrence are poorly documented, especially in the pediatric population. Exchange cranioplasty is an autologous reconstructive surgical option for patients of all ages, and it can be effective in the treatment of large calvarial osteomas. Recurrent lesions of the cranioplasty site have not been well described in the literature, with only 3 documented reports. In this study, we present a unique case of a recurrent osteoma at the site of a prior exchange cranioplasty. The authors also provide a systematic review of the literature for recurrent osteomas and highlight causes and conclusions for these lesions. Utilizing the PRISMA guidelines, a systematic review of articles published across databases was performed to identify accounts of recurrent osteomas at prior cranioplasty sites. Our systematic review illustrates that recurrent osteomas overlying different cranioplasty biomaterials is a rare entity and is due to incomplete resection of the galea and periosteum during the index procedure. Biomaterial selection for the pediatric population requires careful consideration before reconstruction. Though limited by 3 articles previously published and without a direct link to recurrence, long-term studies are needed to further guide biomaterial selection in the pediatric population to evaluate potential recurrences.

Predictors of inpatient mortality following reverse shoulder arthroplasty.

INTRODUCTION: The number of reverse shoulder arthroplasties (RSA) performed each year is growing rapidly, especially in elderly patients and with expanded indications including geriatric proximal humerus fractures. As the elderly population grows and the number of RSA's annually continues to rise, there will be a proportionate number of adverse events and mortality. However, the rate of early mortality has consistently shown to be less than 1%, so a large-scale analysis of possible risk factors for post-operative mortality is warranted. METHODS: A retrospective multivariate analysis of 59,915 patients from the National Inpatient Sample database between 2016 and 2019 was performed. Patients who underwent RSA were identified based on ICD-10 code. Patients were divided into two groups, early mortality and no mortality. Early mortality was defined as those who died within the same admission. Patient demographics and medical comorbidities were evaluated. Hospital admission status was classified as elective or non-elective. Odds ratios for predictive variables were measured as a ratio of incidence between the early mortality and no mortality groups. RESULTS: The overall incidence of inpatient mortality was 0.07%. The incidence of mortality for elective admissions was 0.04% and for non-elective admissions was 0.34%. On univariate analysis, age greater than 75 years (p < 0.001), octogenarians (p < 0.001), nonagenarians (p < 0.001), and non-elective admission (p < 0.001) were associated with early mortality following RSA. Upon multivariate analysis, age greater than 75 years old had 4 times the odds of early mortality following RSA (OR 4.20; 95%CI (1.67, 10.60); p < 0.001) while non-elective admission had about 5 times the odds (OR 5.38; 95%CI (2.75, 10.53); p < 0.001). DISCUSSION: Age greater than 75 years old has 4-fold higher odds and non-elective admission has 5-fold higher odds of early mortality following RSA. Appropriate pre-operative counseling should be performed with elderly patients and those undergoing non-elective indications for RSA.

Prolonged deprivation of arginine or leucine induces PI3K/Akt-dependent reactivation of mTORC1.

The mechanistic target of rapamycin complex 1 (mTORC1) is a serine/threonine kinase complex that promotes anabolic processes including protein, lipid, and nucleotide synthesis, while suppressing catabolic processes such as macroautophagy. mTORC1 activity is regulated by growth factors and amino acids, which signal through distinct but integrated molecular pathways: growth factors largely signal through the PI3K/Akt-dependent pathway, whereas the availabilities of amino acids leucine and arginine are communicated to mTORC1 by the Rag-GTPase pathway. While it is relatively well described how acute changes in leucine and arginine levels affect mTORC1 signaling, the effects of prolonged amino acid deprivation remain less well understood. Here, we demonstrate that prolonged deprivation of arginine and/or leucine leads to reactivation of mTORC1 activity, which reaches activation levels similar to those observed in nutrient-rich conditions. Surprisingly, we find that this reactivation is independent of the regeneration of amino acids by canonical autophagy or proteasomal degradation but is dependent on PI3K/Akt signaling. Together, our data identify a novel crosstalk between the amino acid and PI3K/Akt signaling pathways upstream of mTORC1. These observations extend our understanding of the role of mTORC1 in growth-related diseases and indicate that dietary intervention by removal of leucine and/or arginine may be an ineffective therapeutic approach.

Seizure outcomes after resection of primary brain tumors in pediatric patients: a systematic review and meta-analysis.

PURPOSE: Primary brain neoplasms are the most common solid tumors in pediatric patients and seizures are a common presenting symptom. Surgical intervention improves oncologic outcomes and seizure burden. A better understanding of factors that influence seizure outcomes in the surgical management of primary brain tumors of childhood can guide treatment approach thereby improving patient quality of life. METHODS: We performed a systematic analysis using articles queried from PubMed, EMBASE, and Cochrane published from January 1990 to August 2022 to determine predictors of seizure outcomes in pediatric patients undergoing resection of primary brain tumors. RESULTS: We identified 24 retrospective cohort studies, one prospective cohort study, and one mixed retrospective and prospective study for the systematic analysis. A total of 831 pediatric patients were available for analysis. 668 (80.4%) patients achieved seizure freedom after surgery. Complete tumor resection increased the likelihood of a seizure-free (Engel I) outcome compared to subtotal resection (OR 7.1, 95% CI 2.3-21.9). Rates of Engel I seizure outcomes did not significantly differ based on factors such as age at seizure onset, duration of epilepsy, gender, tumor laterality, or age at surgery, but trended towards significance for improved outcomes in temporal lobe tumors. CONCLUSION: Primary brain tumors in the pediatric population are commonly associated with seizures. Resection of these lesions reduces seizure burden and is associated with high rates of seizure freedom. Complete resection, compared to subtotal resection, significantly increases the likelihood of seizure-free outcomes.

Clinical outcomes of stereotactic biopsy on children with pontine diffuse midline glioma.

INTRODUCTION: Diffuse midline glioma (DMG) of the pons occurs in pediatric patients and carries a dismal prognosis. Biopsy is not necessary for diagnosis but provides information, particularly H3K27M status, with prognostic implications. Additionally, biopsy information may open therapeutic options such as clinical trials that require mutation status. Therefore, we sought to assess the safety of surgical biopsy in DMG patients as well as its potential impact on clinical course. METHODS: Retrospective analysis of patients who were radiographically and clinically diagnosed with pontine DMG in the last 5 years was performed. We assessed demographic, clinical, radiographic, surgical, and follow-up data. RESULTS: 25 patients were included; 18 (72%) underwent biopsy while 7 (28%) declined. 12 biopsies (67%) were performed with robotic arm and 5 (27%) with frameless stereotaxy. Three biopsied patients (17%) experienced new post-operative neurologic deficits (1 facial palsy, 1 VI nerve palsy and 1 ataxia) that all resolved at 2-week follow-up. All biopsies yielded diagnostic tissue. Fourteen patients (78%) had H3K27M mutation. Median OS for H3K27M patients was 10 months compared to 11 months in the wild-type patients (p = 0.30, log-rank test). Median OS for patients enrolled in clinical trials was 12 months compared to 8 months for non-trial patients (p = 0.076). CONCLUSION: In our series, stereotactic pontine DMG biopsies did not carry any permanent deficit or complication and yielded diagnostic tissue in all patients. Similar post-operative course was observed in both robot-assisted and frameless stereotactic approaches. There was no significant difference in survival based on mutation status or clinical trial enrollment.

Behavioral Improvements following Lesion Resection for Pediatric Epilepsy: Pediatric Psychosurgery?

INTRODUCTION: Resection of brain lesions associated with refractory epilepsy to achieve seizure control is well accepted. However, concurrent behavioral effects of these lesions such as changes in mood, personality, and cognition and the effects of surgery on behavior have not been well characterized. We describe 5 such children with epileptogenic lesions and significant behavioral abnormalities which improved after surgery. CASE DESCRIPTIONS: Five children (ages 3-14 years) with major behavioral abnormalities and lesional epilepsy were identified and treated at our center. Behavioral problems included academic impairment, impulsivity, self-injurious behavior, and decreased social interaction with diagnoses of ADHD, oppositional defiant disorder, and autism. Pre-operative neuropsychiatric testing was performed in 4/5 patients and revealed low-average cognitive and intellectual abilities for their age, attentional difficulties, and poor memory. Lesions were located in the temporal (2 gangliogliomas, 1 JPA, 1 cavernoma) and parietal (1 DNET) lobes. Gross total resection was achieved in all cases. At mean 1-year follow-up, seizure freedom (Engel 1a in 3 patients, Engel 1c in 2 patients) and significant behavioral improvements (academic performance, attention, socialization, and aggression) were achieved in all. Two patients manifested violence pre-operatively; one had extreme behavior with violence toward teachers and peers despite low seizure burden. Since surgery, his behavior has normalized. CONCLUSION: We identified 5 patients with severe behavioral disorders in the setting of lesional epilepsy, all of whom demonstrated improvement after surgery. The degree of behavioral abnormality was disproportionate to epilepsy severity, suggesting a more complicated mechanism by which lesional epilepsy impacts behavior. We propose a novel paradigm in which lesionectomy may offer behavioral benefit even when seizures are not refractory. Thus, behavioral improvement may be an important novel goal for neurosurgical resection in children with epileptic brain lesions.

The institutional experience of the implementing 4DCT in NSCLC radiotherapy planning.

Background: The study was to evaluate the effectiveness of dose distribution of four-dimensional computed tomography (4DCT) simulation. Materials and methods: The gross tumor volume (GTV) and clinical target volume (CTV) were contoured in all 10 respiratory phases of 4DCT in 30 patients with non-small cell lung cancer (NSCLC). Both 3D and 4D treatment plans were made individually for each patient using the planning volume (PTV). The PTV3D was taken from a single CTV plus the recommended margin, and the PTV4D was taken from the 4D internal target volume, including all 10 CTVs plus the setup margins. Results: The mean PTV was 460 ± 179 (69-820) cm3 for 3DCT and 401 ± 167 (127-854) cm3 for 4DCT (p = 0.0018). The dose distribution (DD) of organs at risk, especially the lungs, was lower for the 4DCT simulation. The V5%, V10%, and V20% of the total lung dose for 4DCT were significantly lower for the 3DCT. However, lung V30% the heart, esophagus, and spinal cord were not significantly different. In addition, the conformity index and the dose heterogeneity index of the PTV were not significantly different. The normal tissue complication probability (NTCP) of the lung and heart was significantly lower for 4DCT than for 3DCT. Conclusions: The 4DCT simulation gives better results on the NTCP. The organs at risk, especially the lungs, receive a significantly lower DD compared with the 3DCT. The conformity index (CI), heterogeneity index (HI) and the DD to the heart, spinal cord, and esophagus were not significantly different between the two techniques.

Prospective role and immunotherapeutic targets of sideroflexin protein family in lung adenocarcinoma: evidence from bioinformatics validation.

As lung cancer remains the leading cause of cancer deaths globally, characterizing the tumor molecular profiles is crucial to tailoring treatments for individuals at advanced stages. Cancer cells exhibit strong dependence on iron for their proliferation, and several iron-regulatory proteins have been proposed as either oncogenes or tumor suppressive genes. This study aims to evaluate the prospective therapeutic and prognostic values of the sideroflexin (SFXN) gene family, whose functions involve mitochondrial iron metabolism, in lung adenocarcinoma (LUAD). Differential expression analysis using TIMER and UALCAN tools was first employed to compare SFXNs expression levels between normal and LUAD tissues. Next, SFXNs' prognostic values, biological significance, and potential as immunotherapy candidates were examined from GEPIA, cBioPortal, MetaCore, Cytoscape, and TIMER databases. It was found that all members of SFXN family, except SFXN3, were differentially expressed in LUAD compared to normal samples and within different stages of LUAD. Survival analysis then revealed SFXN1 to be related to worse overall survival outcome in patients with LUAD. Furthermore, several correlations between expression of SFXN1 and immune infiltration cells were discovered. To conclude, our study provides evidence of SFXN family gene's relevance to the prognosis and immunotherapeutic targets of LUAD.

Vitamin D intake and gastric cancer in Viet Nam: a case-control study.

BACKGROUND: Most recent laboratory studies have suggested a promising role of vitamin D and its analogs as novel chemotherapeutic agents for cancer treatment. However, epidemiological evidence, especially regarding the effects of vitamin D on gastric cancer is still inconsistent. OBJECTIVES: Our research aimed to evaluate the associations between vitamin D intake and the risk of developing gastric cancer through a case-control study in North Vietnam. METHODS: We accessed databases of the previous completed case-control studies to derive 1182 incident gastric cancer cases and 2995 hospital controls selected from hospitals in Hanoi from 2003 to 2019. Vitamin D intake was computed by multiplying the food frequency intake with nutrient content based on the Viet Nam Food Composition Tables. Data were collected through face-to-face interviews by trained interviewers using the validated semi-quantitative food frequency and demographic lifestyle questionnaires. The odds ratio and 95% confidence interval (OR and 95%CI) were estimated using unconditional logistic regression analysis. RESULTS: We observed a continual decline in gastric cancer risk according to the level-up of vitamin D intake in both genders, men, and women [Fifth vs. bottom quintile, OR, 95%CI: 0.68 (0.53, 0.86), OR, 95%CI: 0.72 (0.53, 0.97), OR, 95%CI: 0.58 (0.38, 0.89), respectively. Per increment quintile, the statistically significant decreased risk was seen by 7% in men and 13% in women. The significant inverse association between vitamin D intake remained in the subgroups of ever and never tobacco smoking; negative and positive H. pylori infection. CONCLUSION: The findings suggested that sufficient vitamin D intake was associated with a lower risk of Gastric Cancer in the Vietnamese population.

Organic food purchase decisions from a context-based behavioral reasoning approach.

While the burgeoning development of organic foods has received great interest from academicians, the green gap has been posing challenges to the understanding of the inconsistency between consumers' actions and their positive intentions towards organic foods. The latest marketing literature has pointed to the potential of the cognitive and reasoning process taking into account context-specificity as the answer to the problem. Applying the novel Behavioral Reasoning Theory, this study sets out to bridge this gap by providing insights into the context-based reasoning process of Vietnamese consumers. PLS-SEM method was employed to test the proposed hypotheses between values, reasons, attitudes, behavioral intention, and actual purchase behavior among 300 consumers from two big cities (i.e., Hanoi and Ho Chi Minh) in Vietnam. The mediation analysis was conducted for reasons and attitudes. The model was also extended using trust and knowledge factors. Overall, the results suggested the strong cognitive routes originated from values onto reasons and attitudes, whereas attitudes and reasons (for and against) positively influenced purchase intentions. Additionally, the mediational effects of both reasons and attitudes were not established. Trust was found strengthening reasons for and attitudes while mitigating reasons against. Consumers' knowledge rendered impacts on intentions but not attitudes. Useful implications for academicians, marketers, and policymakers were also discussed.

Moderate Weightbearing Restrictions Are Associated with Worse Depressive Symptoms and Anxiety in Children Aged 5 to 7 Years with Perthes Disease.

BACKGROUND: Perthes disease most commonly affects children 5 to 7 years old, and nonoperative management, such as weightbearing and activity restrictions, is generally recommended. In earlier research in children aged 8 to 14 years who had Perthes disease, we found that the restrictions were associated with worse mobility, but mental health or social health measures were not linked. However, Perthes disease most commonly affects children 5 to 7 years old who are more emotionally and cognitively immature. Children in this age group are beginning school and organized sports experiences while developing meaningful social relationships for the first time. Because of such different life experiences, it is important to understand the psychosocial consequences of weightbearing and activity restrictions on this specific age group, as they may help guide choices about weightbearing restrictions and mental health support. QUESTIONS/PURPOSES: In patients aged 5 to 7 years with Perthes disease, we asked: (1) Are weightbearing and activity restrictions associated with worse mental health, evaluated with the Patient-reported Outcome Measurement Information System (PROMIS) depressive symptoms, anxiety, and anger questionnaires? (2) Are weightbearing and activity restrictions associated with worse social health (PROMIS peer relationships measure)? (3) Are weightbearing and activity restrictions associated with worse physical health measures (PROMIS mobility, pain interference, and fatigue measures)? (4) What other factors are associated with mental, social, and physical health measures in these patients? METHODS: Data were collected from 97 patients with a diagnosis of Perthes disease. Inclusion criteria were age 5 to 7 years at the time the PROMIS was completed, English-speaking patients and parents, in the active stage of Perthes disease (Waldenstrom Stages I, II, or III) who were recommended weightbearing and activity restrictions because of worsening hip pain, poor hip ROM, femoral head deformity, as a postoperative regimen, or if there was substantial femoral head involvement on MRI [23]. Based on their weightbearing and activity restriction regimen, patients were categorized into one of four activity restriction groups (no, mild, moderate, and severe restriction). The following pediatric parent-proxy PROMIS measures were obtained: depressive symptoms, anxiety, anger, peer relationships, mobility, pain interference, and fatigue. We excluded five patients who did not meet the inclusion criteria. Of the remaining 92 patients, 21 were in the no restriction group, 21 were in the mild restriction group, 28 were in the moderate restriction group, and 22 were in the severe restriction group at the time of PROMIS administration. ANOVA was used to compare differences between the mean PROMIS T-scores of these four groups. T-scores are computed from PROMIS survey responses, and a T-score of 50 represents the age-appropriate mean of the US population with an SD of 10. A higher T-score means more of that measure is being experienced and a lower score means less of that measure is being experienced. To address the possibility of confounding variables such as Waldenstrom stage, gender, age at diagnosis, and history of major surgery, we performed a multivariable analysis to compare the association of different weightbearing regimens and the seven PROMIS measures. This allowed us to answer the question of whether weightbearing and activity restrictions are associated with worse physical, mental, and social health measures in Perthes patients aged 5 to 7 years, while minimizing the possible confounding of the variables listed above. RESULTS: After controlling for confounding variables such as Waldenstrom stage, gender, age at diagnosis, and history of major surgery, we found that moderate activity restriction was associated with worse depressive symptoms (ß regression coefficient = 6 [95% CI 0.3 to 12]; p = 0.04) and anxiety (ß = 8 [95% CI 1 to 15]; p = 0.02) T-scores than no restrictions. The mild (ß = -7 [95% CI -12 to -1]; p = 0.02), moderate (ß = -15 [95% CI -20 to -10]; p < 0.001), and severe (ß = -23 [95% CI -28 to -18]; p < 0.001), restriction groups had worse mobility T-scores than the no restriction group. Weightbearing and activity restrictions were not associated with anger, peer relationships, pain interference, and fatigue measures. Waldenstrom Stage II disease was associated with worse pain interference than Waldenstrom Stage III (ß = 7 [95% CI 0.4 to 13]; p = 0.04). A history of major surgery was associated with worse anger scores (ß = 18 [95% CI 3 to 33]; p = 0.02). The child's gender and age at diagnosis had no association with any of the seven PROMIS measures. CONCLUSION: Moderate weightbearing and activity restrictions are associated with worse depressive symptoms and anxiety in patients with Perthes disease aged 5 to 7 years, after controlling for Waldenstrom stage, gender, age at the time of diagnosis, and history of surgery. Considering the discoveries in this study and in our previous study, for patients 5 to 7 years old, we recommend that providers discuss the potential for mental health changes with moderate weightbearing restrictions with patients and their families. Furthermore, providers should monitor for worsening mental health symptoms at each follow-up visit and refer patients to a clinical child psychologist for support when appropriate. Future studies are needed to assess the effects of these restrictions on mental health over time and after patients are allowed to return to normal activities. LEVEL OF EVIDENCE: Level III, therapeutic study.

Weightbearing and Activity Restriction Treatments and Quality of Life in Patients with Perthes Disease.

BACKGROUND: Weightbearing and activity restrictions are commonly prescribed during the active stages of Perthes disease. These restrictions, ranging from cast or brace treatment with nonweightbearing to full weightbearing with activity restrictions, may have a substantial influence on the physical, mental, and social health of a child. However, their impact on the patient's quality of life is not well-described. QUESTIONS/PURPOSES: After controlling for confounding variables, we asked (1) are restrictions on weightbearing and activity associated with physical health measures (as expressed by the Patient-Reported Outcome Measurement Information System [PROMIS] mobility, PROMIS pain interference, and PROMIS fatigue) of children in the active stages of Perthes disease? (2) Are these restrictions associated with poorer scores for mental health measures (PROMIS depressive symptoms and PROMIS anxiety)? (3) Are these restrictions associated with poorer scores for social health measures (PROMIS peer relationships)? METHODS: Between 2013 and 2020, 211 patients with Perthes disease at a single institution were assigned six PROMIS measures to assess physical, mental, and social health. Patients who met the following eligibility criteria were analyzed: age 8 to 14 years old, completion of six PROMIS measures, English-speaking, and active stage of Perthes disease (Waldenstrom Stage I, II, or III). Weightbearing and activity restrictions were clinically recommended to patients in the initial through early reossification stages of Perthes disease when patients had increasing pain, loss of hip motion, loss of hip containment, progression of femoral head deformity, increased hip synovitis, and femoral head involvement on MRI or as a postoperative regimen. Patients were categorized into four intervention groups based on weightbearing and activity regimen. We excluded 111 patients who did not meet the inclusion criteria. The following six pediatric self-report PROMIS measures were assessed: mobility, pain interference, fatigue, depressive symptoms, anxiety, and peer relationships. Of the 100 patients, 36 were categorized into the no-restriction regimen, 27 into the mild-restriction regimen, 25 into the moderate-restriction regimen, and 12 into the severe-restriction regimen at the time of PROMIS administration. The median (range) age at diagnosis was 8 years old (range 2 to 13 years). There were 85 boys and 15 girls. Eleven patients had hips in Waldenstrom Stage I, 10 were in Stage II, and 79 were in Stage III. Forty-four patients had hips classified as lateral pillar B and 47 patients as lateral pillar C. Nine patients had not reached the mid-fragmentation stage for appropriate lateral pillar classification by the time they took the PROMIS survey. ANOVA was used to compare differences between the mean PROMIS T-scores of these weightbearing/activity regimens. Results were assessed with a significance of p < 0.05 and adjusted for Waldenstrom stage, gender, age at diagnosis, and history of major surgery using multivariate regression analysis. RESULTS: After controlling for confounding variables, the mild- (ß regression coefficient -15 [95% CI -19 to -10]; p < 0.001), moderate- (ß -19 [95% CI -24 to -14]; p < 0.001), and severe- (ß -25 [95% CI -30 to -19]; p < 0.001) restriction groups were associated with worse mobility T-scores compared with the no-restriction group, but no association was detected for the pain interference or fatigue measures. Weightbearing and activity restrictions were not associated with mental health measures (depressive symptoms and anxiety). Weightbearing and activity restrictions were not associated with social health measures (peer relationships). Earlier Waldenstrom stage was associated with worse pain interference (ß 10 [95% CI 2 to 17]; p = 0.01) and peer relationships scores (ß -8 [95% CI -15 to -1]; p = 0.03); female gender was linked with worse depressive symptoms (ß 7 [95% CI 2 to 12]; p = 0.005) and peer relationships scores (ß -6 [95% CI -12 to 0]; p = 0.04); and earlier age at diagnosis was associated with worse peer relationships scores (ß 1 [95% CI 0 to 2]; p = 0.03). History of major surgery had no connection to any of the six PROMIS measures. CONCLUSION: We found that weightbearing and activity restriction treatments are associated with poorer patient-reported mobility in the active stages of Perthes disease after controlling for Waldenstrom stage, gender, age at diagnosis, and history of surgery. Weightbearing/activity restrictions, however, are not associated with pain interference, fatigue, depressive symptoms, anxiety, and peer relationships. Understanding how these treatments are associated with quality of life in patients with Perthes disease can aid in decision-making for providers, help set expectations for patients and their parents, and provide opportunities for better education and preparation. Because of the chronic nature of Perthes disease, future studies may focus on longitudinal trends in patient-reported outcomes to better understand the overall impact of this disease and its treatment. LEVEL OF EVIDENCE: Level III, therapeutic study.

Congenital coronary vein aneurysm: A case report.

A 61-year-old female patient with chest pain was diagnosed with localized pericardial effusion, resistance to medical therapy. Cardiac magnetic resonance imaging revealed a massive aneurysm originating from coronary veins, which was successfully removed.

Totally endoscopic atrial septal defect repair in a patient with interrupted inferior vena cava with azygos-hemiazygos continuation.

Atrial septal defect combined with interrupted inferior vena cava (IVC), which is a rare condition, makes it impossible to apply totally endoscopic surgery (TES). The most difficulty is how to drain blood from the posthepatic segment of the IVC. In this study, we report a case of a 44-year-old female patient who was diagnosed with secundum atrial septal defect combined with interrupted IVC with azygos-hemiazygos continuation. This patient underwent successful repair by TES with transthoracic cannulation for the posthepatic segment of the IVC.

Acoustopipetting: Tunable Nanoliter Sample Dispensing Using Surface Acoustic Waves.

We seek to demonstrate a robust, low-cost, and user-friendly acoustomicrofluidic platform that facilitates rapid, reproducible, and precise nanoliter sample dispensing. The solid-state chipscale platform exploits the unprecedented acceleration arising from high-frequency nanoelectromechanical vibrations, on the order of 10 million g, to jet the sample and hence generate a liquid bridge that spans across the substrate, on which the vibrations are generated and from which the sample originates, to a top target plate before rapidly pinching off to deposit the sample on the target with precise and reproducible volumes that can be tuned down to 0.22 µL with a standard error of 6.5% and coefficient of variation of 11.3%. The entire process occurs within approximately 10 ms. In addition to explicating the fundamental physical mechanism that underpins the technology, we demonstrate its use for serial dilution and concentration and, in particular, a cell-based drug toxicology assay. Moreover, we also show that multiple drop dispensing in an array, without requiring repositioning of the chip between dispensing steps, can be achieved through a simple but yet effective sequential directional jetting strategy, therefore allowing significant reduction in the total dispensing time in the case of massive-scale microarray operation. Given its low cost and compact size, the platform can easily be automated and parallelized, thus offering the prospect for introducing large-scale efficiencies in the laboratory workflow.

Nucling, a novel apoptosis-associated protein, controls mammary gland involution by regulating NF-κB and STAT3.

Postpartum mammary gland involution is the physiological process by which the lactating gland returns to its pre-pregnant state. In rodent models, the microenvironment of mammary gland involution is sufficient to induce enhanced tumor cell growth, local invasion, and metastasis. Therefore, a deeper understanding of the physiological regulation of involution may provide in-depth information on breast cancer therapy. We herein identified Nucling as an important regulator of involution of the mammary gland. A knock-out mouse model was generated and revealed that postpartum involution were impaired in mice lacking Nucling. Involution is normally associated with an increase in the activation of NF-κB and STAT3, which is required for the organized regulation of involution, and was observed in WT glands, but not in the absence of Nucling. Furthermore, the loss of Nucling led to the suppression of Calpain-1, IL-6, and C/EBPδ factors, which are known to be essential for normal involution. The number of M2 macrophages, which are crucial for epithelial cell death and adipocyte repopulation after weaning, was also reduced in Nucling-KO glands. Taken together, the results of the present study demonstrated that Nucling played an important role in mammary gland involution by regulating NF-κB and STAT3 signaling pathways.