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β-Hydroxybutyrate and melatonin suppress maladaptive UPR, excessive autophagy and pyroptosis in Aβ 1-42 and LPS-Induced SH-SY5Y cells

Mol Biol Rep. 2024 Jul 13;51(1):802. doi: 10.1007/s11033-024-09754-5.

ABSTRACT

BACKGROUND: Alzheimer’s disease is a neurological disease characterized by the build-up of amyloid beta peptide (Aβ) and lipopolysaccharide (LPS), which causes synapse dysfunction, cell death, and neuro-inflammation. A maladaptive unfolded protein response (UPR), excessive autophagy, and pyroptosis aggravate the disease. Melatonin (MEL) and hydroxybutyrate (BHB) have both shown promise in terms of decreasing Aβ pathology. The goal of this study was to see how BHB and MEL affected the UPR, autophagy, and pyroptosis pathways in Aβ1-42 and LPS-induced SH-SY5Y cells.

MATERIALS AND METHODS: Human neuroblastoma SH-SY5Y cells were treated with BHB, MEL, or a combination of the two after being exposed to A β1-42 and LPS. Cell viability was determined using the MTT test, and gene expression levels of UPR (ATF6, PERK, and CHOP), autophagy (Beclin-1, LC3II, P62, and Atg5), and pyroptosis-related markers (NLRP3, TXNIP, IL-1β, and NFκB1) were determined using quantitative Real-Time PCR (qRT-PCR). For statistical analysis, one-way ANOVA was employed, followed by Tukey’s post hoc test.

RESULTS: BHB and MEL significantly increased SH-SY5Y cell viability in the presence of A β1-42 and LPS. Both compounds inhibited the expression of maladaptive UPR and autophagy-related genes, as well as inflammatory and pyroptotic markers caused by Aβ1-42 and LPS-induced SH-SY5Y cells.

CONCLUSION: BHB and MEL rescue neurons in A β1-42 and LPS-induced SH-SY5Y cells by reducing maladaptive UPR, excessive autophagy, and pyroptosis. More research is needed to fully comprehend the processes behind their beneficial effects and to discover their practical applications in the treatment of neurodegenerative disorders.

PMID:39001949 | DOI:10.1007/s11033-024-09754-5

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Mesh versus suture for elective primary umbilical hernia open repair: a systematic review and meta-analysis

Hernia. 2024 Jul 13. doi: 10.1007/s10029-024-03106-9. Online ahead of print.

ABSTRACT

PURPOSE: Recent guidelines indicate the use of mesh in UHR for defects > 1 cm, as it reduces recurrence, with 10% recurrence rate compared to up to 54.5% with primary closure. However, Nguyen et al. shows that primary closure is still widely performed in UHR, especially for small defects (1-2 cm), for which there is no published data to determine the optimal approach. In addition, previous meta-analysis by Madsen et al. comparing mesh repair with primary closure in UHR didn’t exclude emergency conditions and recurrent hernias; also, didn’t report subgroup analysis on hernia defect size. Thus, we aimed to perform a systematic review and meta-analysis comparing the mesh repairs vs. primary closure of the defect in an open elective primary UHR.

METHODS: We searched for studies comparing mesh with suture in open UHR in PubMed, Scopus, Cochrane, Scielo, and Lilacs from inception until October 2023. Studies with patients ≤ 18 years old, with recurrent or emergency conditions were excluded. Outcomes were recurrence, seroma, hematoma, wound infection, and hospital length of stay. Subgroup analysis was performed for: (1) RCTs only, and (2) hernia defects smaller than 2 cm. We used RevMan 5.4. for statistical analysis. Heterogeneity was assessed with I² statistics, and random effect was used if I² > 25%.

RESULTS: 2895 studies were screened and 56 were reviewed. 12 studies, including 4 RCTs, 1 prospective cohort, and 7 retrospective cohorts were included, comprising 2926 patients in total (47.6% in mesh group and 52.4% in the suture group). Mesh repair showed lower rates of recurrence in the overall analysis (RR 0.50; 95% CI 0.31 to 0.79; P = 0.003; I2 = 24%) and for hernia defects smaller than 2 cm (RR 0.56; 95% CI 0.34 to 0.93; P = 0.03; I2 = 0%). Suture repair showed lower rates of seroma (RR 1.88; 95% CI 1.07 to 3.32; P = 0.03; I2 = 0%) and wound infection (RR 1.65; 95%CI 1.12 to 2.43; P = 0.01; I2 = 15%) in the overall analysis, with no differences after performing subgroup analysis of RCTs. No differences were seen regarding hematoma and hospital length of stay.

CONCLUSION: The use of mesh during UHR is associated with significantly lower incidence of recurrence in a long-term follow-up compared to the suture repair, reinforcing the previous indications of the guidelines. Additionally, despite the overall analysis showing higher risk of seroma and wound infection for the suture repair, no differences were seen after subgroup analysis of RCTs.

STUDY REGISTRATION: A review protocol for this systematic review and meta-analysis was registered at PROSPERO (CRD42024476854).

PMID:39001938 | DOI:10.1007/s10029-024-03106-9

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When to trust an AI model

A new technique enables huge machine-learning models to efficiently generate more accurate quantifications of their uncertainty about certain predictions. This could help practitioners determine whether to trust the model when it is deployed in real-world settings.
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Nevin Manimala Statistics

Children and families with chronic pediatric acquired brain injury in need of rehabilitation: characteristics and main challenges in daily life

Disabil Rehabil. 2024 Jul 13:1-10. doi: 10.1080/09638288.2024.2376936. Online ahead of print.

ABSTRACT

PURPOSE: To increase our understanding of child and parent characteristics, family functioning and main challenges in daily life in children and families in need of rehabilitation in the chronic phase of pediatric acquired brain injury (pABI).

METHODS: Fifty-eight children (aged 6-16, 48% girls) were included at least one year post ABI. Demographics and questionnaire data regarding children’s symptom burden, parents’ emotional symptoms and family functioning were collected. Children and parents named their main pABI-related challenges in daily life, and these were categorized in accordance with the International Classification of Functioning, Disability and Health (ICF). Descriptive statistical analyses were performed.

RESULTS: Parents’ emotional symptom loads were high; 22.3% had moderate, moderate-severe or severe depression symptoms while the equivalent number for anxiety symptoms was 17.9%. Problematic family functioning was reported by 32.1% of parents. When asked about their main pABI-related challenges in daily life, 69% of children named school. The most frequent ICF chapters for children and parents were school education, energy and drive functions (mainly fatigue), and emotional functions. Codes spanned across all ICF-domains.

CONCLUSIONS: Rehabilitation for pABI should have a broad, interdisciplinary, and family-centered approach, with school, fatigue, and emotional functioning of parents and children as potential core elements.

PMID:39001694 | DOI:10.1080/09638288.2024.2376936

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Fetal thymus size in pregnant women with Hashimoto disease

J Clin Ultrasound. 2024 Jul 13. doi: 10.1002/jcu.23764. Online ahead of print.

ABSTRACT

PURPOSE: This study compared fetal thymic-thoracic ratios and fetal thymus transverse diameter measurements in pregnant women with Hashimoto’s thyroiditis (HT) and non-immune hypothyroidism.

METHODS: The study included a total of 141 pregnant women in three groups: 41 with HT, 50 with non-immune hypothyroidism, and 50 healthy individuals. Fetal thymus transverse diameter and thymic-thoracic ratio were compared between these groups.

RESULTS: The mean fetal thymic-thoracic ratio was greater in pregnant women with HT than in the healthy controls (p = 0.031). Mean fetal thymus transverse diameter showed no statistically significant difference between the groups.

CONCLUSIONS: Maternal HT was associated with an increased fetal thymic-thoracic ratio. More comprehensive studies are needed on this subject.

PMID:39001684 | DOI:10.1002/jcu.23764

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Trends in primary care blood tests prior to lung and colorectal cancer diagnosis-A retrospective cohort study using linked Australian data

Cancer Med. 2024 Jul;13(14):e70006. doi: 10.1002/cam4.70006.

ABSTRACT

INTRODUCTION: Abnormal results in common blood tests may occur several months before lung cancer (LC) and colorectal cancer (CRC) diagnosis. Identifying early blood markers of cancer and distinct blood test signatures could support earlier diagnosis in general practice.

METHODS: Using linked Australian primary care and hospital cancer registry data, we conducted a cohort study of 855 LC and 399 CRC patients diagnosed between 2001 and 2021. Requests and results from general practice blood tests (six acute phase reactants [APR] and six red blood cell indices [RBCI]) were examined in the 2 years before cancer diagnosis. Poisson regression models were used to estimate monthly incidence rates and examine pre-diagnostic trends in blood test use and abnormal results prior to cancer diagnosis, comparing patterns in LC and CRC patients.

RESULTS: General practice blood test requests increase from 7 months before CRC and 6 months before LC diagnosis. Abnormalities in many APR and RBCI tests increase several months before cancer diagnosis, often occur prior to or in the absence of anaemia (in 51% of CRC and 81% of LC patients with abnormalities), and are different in LC and CRC patients.

CONCLUSIONS: This study demonstrates an increase in diagnostic activity in Australian general practice several months before LC and CRC diagnosis, indicating potential opportunities for earlier diagnosis. It identifies blood test abnormalities and distinct signatures that are early markers of LC and CRC. If combined with other pre-diagnostic information, these blood tests have potential to support GPs in prioritising patients for cancer investigation of different sites to expedite diagnosis.

PMID:39001673 | DOI:10.1002/cam4.70006

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Diagnostic accuracy of voluntary and stimulated neuromuscular jitter studies in ocular myasthenia gravis

Muscle Nerve. 2024 Jul 13. doi: 10.1002/mus.28202. Online ahead of print.

ABSTRACT

INTRODUCTION/AIMS: There is a lack of studies comparing the accuracy of neuromuscular jitter analysis during voluntary activation (v-jitter study) versus axonal stimulation (s-jitter study). The study aimed to compare these two techniques in the same population of patients with suspected ocular myasthenia gravis (OMG).

METHODS: Fourteen control subjects (mean age: 55.5 ± 15.2 years) and 34 patients with suspected OMG (mean age: 59 ± 13.9 years) were prospectively evaluated. Twenty spike pairs and 30 individual spikes were analyzed during v-jitter and s-jitter study, respectively. Two different criteria for abnormal individual jitter values were evaluated: ≥ or > than 10% values exceeding the upper normal limit.

RESULTS: OMG was diagnosed in 19 patients based on clinical and laboratory findings, without considering jitter measurements. In most patients, v-jitter and s-jitter analyses provided comparable results. The maximum sensitivity (89%) was achieved with s-jitter study using the ≥10% criterion, while the maximum specificity (93%) was found with v-jitter study using the >10% criterion.

DISCUSSION: Both v-jitter and s-jitter studies showed good to very good accuracy for the diagnosis of OMG, in the absence of any statistically significant difference. Therefore, the patient’s cooperation level and examiner’s experience should guide the choice of performing v-jitter or s-jitter analysis in patients with suspected OMG.

PMID:39001646 | DOI:10.1002/mus.28202

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Validating motor delays across the developmental coordination disorder-questionnaire and the Vineland adaptive behavior scales (VABS) in children with autism spectrum disorderASD: A SPARK dataset analysis

Autism Res. 2024 Jul 13. doi: 10.1002/aur.3189. Online ahead of print.

ABSTRACT

Motor delays in children with autism spectrum disorder (ASD) are being increasingly recognized using a brief screening tool, called the Developmental Coordination Disorder-Questionnaire (DCD-Q). Further validation of these motor delays using a more robust normed, developmental measure is clearly warranted. In this analysis, a nationally representative sample from the SPARK study was used wherein parents completed the DCD-Q and a more widely used developmental/adaptive functioning measure, called the Vineland Adaptive Behavior Scales (VABS); which comprises of various developmental domains including the motor domain (N = 2,644 completed the DCD-Q and VABS). Eighty two percent children with ASD had a motor delay based on their DCD-Q scores whereas 77% children with ASD had a motor delay based on their VABS motor domain scores. Approximately 70% children with ASD had concurrent motor delay on the DCD-Q and the VABS (i.e., positive predictive value of DCD-Q). Furthermore, there was 81.2% accuracy in reporting a risk/no risk of motor delay across both measures. Overall, these statistics align with the recent reports on proportions of children with ASD having motor delays. Parents of ~70% children with ASD are reporting motor delays that are corroborated across two different motor measures. This not only validates the motor delays reported based on the DCD-Q but also indicates the need for concurrent motor screening using both DCD-Q and VABS for better detection of motor delays in children with ASD. Only 10%-32% of the current SPARK sample received any physical or recreational therapies. This mismatch between presence of motor delays and the lack of access to motor services highlights the need for more motor intervention referrals for children with ASD.

PMID:39001643 | DOI:10.1002/aur.3189

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Radiological cervical foraminal stenosis severity and morphology as a predictor of pre-operative function and functional surgical outcome

Br J Neurosurg. 2024 Jul 12:1-9. doi: 10.1080/02688697.2024.2376647. Online ahead of print.

ABSTRACT

BACKGROUND: Cervical foraminal stenosis on MRI may be assessed using the Kim, modified Kim or Siller methods. This study aimed to investigate which morphological features of cervical foraminal stenosis in patients with cervical radiculopathy correlated best with pre-operative and post-operative surgical outcome following Anterior Cervical Discectomy (ACD) or a Posterior Cervical Foraminotomy (PCF).

METHODS: Pre-operative MRIs of adults with cervical radiculopathy were assessed by six raters. The following measurements were made; uncompressed nerve root diameter, maximal compressed nerve root diameter, anterior & posterior compression, length of the neuroforaminal canal where the diameter was less than the uncompressed nerve root diameter and the distance of maximum compression from the apex of the ligamentum flavum. The Kim, modified Kim and Siller grades were calculated. Neck Disability Index (NDI) was measured pre-operatively and six weeks post-operatively. The radiological measurements and grades were compared to the pre-operative and change in NDI.

RESULTS: Mean NDI was higher in female (58.2) than male patients (45.6) p = 0.05. No other baseline, operative or radiological factors where significantly associated with the pre-operative NDI. The mean [±SD] post-operative NDI was 14.3 [±22.5]. This represents a change of 37.8 (p < 0.001). The pre-operative NDI correlated strongly with the post-operative NDI but no other patient, operation or radiological factors correlated significantly. Neither pre-operative NDI or change in NDI was statistically different in those treated with ACD and those treated with PCF.

CONCLUSION: There was no association between pre-operative NDI and any of the radiological measurements or radiological grades. Furthermore, whilst surgery significantly improved NDI, for those patients with anterior compression, there was no difference in outcome between those treated with an ACD and those treated with a PCF. Current axial MRIs do not adequately assess the cervical nerve root foramina or predict surgical approach, 3D isotropic acquisition and DTI should be explored.

PMID:39001642 | DOI:10.1080/02688697.2024.2376647

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Complications and putative risk factors for cecal or colonic surgery in dogs: 79 cases (2002-2015)

J Small Anim Pract. 2024 Jul 12. doi: 10.1111/jsap.13763. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the complication rate, mortality rate and putative risk factors for cecal or colonic surgery in dogs.

MATERIALS AND METHODS: A multi-institutional retrospective study including dogs that had undergone surgery that involved the cecum or the colon. Medical records from three referral hospitals were reviewed for patient demographics and clinical data. The association between putative risk factors and survival to discharge or complications was assessed using univariable and multivariable analysis.

RESULTS: Seventy-nine dogs met the criteria to be included in this study. Fifty-five dogs had full thickness incision surgeries, while 24 dogs had partial thickness surgeries. The complication and mortality rates for full thickness and partial thickness cecal/colonic surgeries were not statistically different. The dehiscence rate of colonic anastomosis in this study was four of 47 (8.5%). On univariate analysis, performing full thickness procedures out of hours had an association with increased complications and mortality. On multivariable analysis, no factors were associated with survival to discharge or complications. There was no association of board-certified surgeon presence in surgery with complications or mortality.

CLINICAL SIGNIFICANCE: The performance of full thickness cecal/colonic surgery is not associated with a statistically significant increased risk for complications or mortality compared to partial thickness procedures, with a possible increased risk of complications and mortality in full thickness procedures out of hours.

PMID:39001633 | DOI:10.1111/jsap.13763