Navigating therapeutic prospects by modulating autophagy in colorectal cancer.

Colorectal cancer (CRC) remains a leading cause of death globally despite the improvements in cancer treatment. Autophagy is an evolutionarily conserved lysosomal-dependent degradation pathway that is critical in maintaining cellular homeostasis. However, in cancer, autophagy may have conflicting functions in preventing early tumour formation versus the maintenance of advanced-stage tumours. Defective autophagy has a broad and dynamic effect not just on cancer cells, but also on the tumour microenvironment which influences tumour progression and response to treatment. To add to the layer of complexity, somatic mutations in CRC including tumour protein p53 (TP53), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), Kirsten rat sarcoma viral oncogene homolog (KRAS), and phosphatase and tensin homolog (PTEN) can render chemoresistance by promoting a pro-survival advantage through autophagy. Recent studies have also reported autophagy-related cell deaths that are distinct from classical autophagy by employing parts of the autophagic machinery, which impacts strategies for autophagy regulation in cancer therapy. This review discusses the molecular processes of autophagy in the evolution of CRC and its role in the tumour microenvironment, as well as prospective therapeutic methods based on autophagy suppression or promotion. It also highlights clinical trials using autophagy modulators for treating CRC, underscoring the importance of autophagy regulation in CRC therapy.

A single centre experience of prosthetic joint infection outcomes with outpatient parenteral antimicrobial therapy.

Objectives: Prosthetic joint infection (PJI) is a serious complication following arthroplasties. This study assessed the clinical outcomes, readmission rates and financial impact of PJIs treated with outpatient parenteral antimicrobial therapy (OPAT). Methods: The study used prospectively collected data from the OPAT patient database at a tertiary care Irish hospital for PJI cases managed between 2015 and 2020. Data was analyzed using IBM-SPSS. Results: Forty-one patients with PJIs were managed via OPAT over five years, with median age of 71.6 years. Median duration of OPAT was 32 days. Hospital readmission occurred in 34% of cases. Reasons for readmission included progression of infection in 64.3%, unplanned reoperation in 21.4% and planned admission for joint revision in 14.3%. Type 2 Diabetes Mellitus (T2DM) was found to have a statistically significant association with unplanned readmission (OR 8.5, CI 95% 1.1-67.6; p < 0.01). OPAT saved a mean of 27.49 hospital-bed days per patient. 1,127 bed days were saved in total, estimating a total savings of 963,585 euros and median savings of 26,505 euros. Conclusions: The readmission rate observed was comparable to international data. Most readmissions were related to primary infections rather than due to OPAT-specific complications. Our main findings were that patients with PJIs can be safely managed via OPAT, and the finding of association between T2DM and increased risk of readmission.

Vaginal Infections during Pregnancy Increase Breast Milk Microbiome Alpha Diversity and Alter Taxonomic Composition.

We previously reported that breast milk from women with (W) or without (WO) vaginal yeast infection during pregnancy differs in its immunological and antimicrobial properties, especially against pathogenic vaginal Candida sp.. Here, we investigated the differences in microbiota profiles of breast milk from these groups. Seventy-two breast milk samples were collected from lactating mothers (W, n=37; WO, n=35). The DNA of bacteria was extracted from each breast milk sample for microbiota profiling by 16S rRNA gene sequencing. Breast milk from the W-group exhibited higher alpha diversity than that from the WO-group across different taxonomic levels of class (P=0.015), order (P=0.011), family (P=0.020), and genus (P=0.030). Compositional differences between groups as determined via beta diversity showed marginal differences at taxonomic levels of phylum (P=0.087), family (P=0.064), and genus (P=0.067). The W-group showed higher abundances of families Moraxellaceae (P=0.010) and Xanthomonadaceae (P=0.008), and their genera Acinetobacter (P=0.015), Enhydrobacter (P=0.015), and Stenotrophomonas (P=0.007). Meanwhile, the WO-group showed higher abundances of genus Staphylococcus (P=0.046) and species Streptococcus infantis (P=0.025). This study shows that, although breast milk composition is affected by vaginal infection during pregnancy, this may not pose a threat to infant growth and development.

Assessment and treatment of depression in people with multiple sclerosis: A qualitative analysis of specialist clinicians' experiences.

BACKGROUND: Depression is common in people with multiple sclerosis (MS), with lifetime prevalence estimates between 25 and 50%. Depression is commonly underdiagnosed and undertreated in people with MS. This qualitative study assessed current practices, as well as facilitators and required resources to improve detection and management of depression in people with MS. METHODS: MS clinicians living in Australia were recruited through MS healthcare provider clinics and networks for online interviews. Interviews were transcribed and coded in NVivo for framework analysis. RESULTS: Participants included 15 MS specialists: nine nurses and six neurologists. Participants appreciated that depression was a common symptom of MS, and that untreated depression impacted patients' wellbeing, medication adherence, capacity for self-care, employment, and interpersonal relationships. Participants did not routinely screen for depression and noted that they lack the time and skills to manage depression once identified, most often recommending patients see their general practitioner. Clinicians recognised that people with MS commonly experience barriers to identifying and managing depressive symptoms, however few clinics provide information or discussion about depression as a symptom of MS with patients. CONCLUSION: Participants indicated a need for evidence-based guidance, more education and training to improve practices including screening for depression, and an urgent need for local referral pathways to affordable and accessible mental health services for people with MS. Findings suggest a need for better collaborative management of depression and improvement of systematic practices related to depression information, screening and treatment support.

Improving the detection and treatment of depression in Australians with multiple sclerosis: A qualitative analysis.

BACKGROUND: Depression is common in people with multiple sclerosis (MS), yet often goes undetected, untreated or undertreated. OBJECTIVE: This qualitative research explored current practices, barriers and facilitators for detection and treatment of depression in Australians with MS. METHODS: Participants were 26 people with MS recruited through social media. Participants completed the Centre for Epidemiological Studies Depression-Revised (CESD-R) scale and in-depth telephone or video interviews. Interviews were analysed using framework analysis. RESULTS: Scores measured on the CESD-R proposed 73% of participants were experiencing severe depression symptoms. Participants reported that depression is not regularly and formally assessed through MS healthcare services and they are offered limited information about depression in MS. Barriers to mental health support included recognition of depression, resistance to treatment and limitations of collaborative support between general practitioners and MS healthcare services. Participants expressed a need for open conversations and information about depression during neurology consultations. CONCLUSION: Based on our findings, improved detection and treatment of depression in people with MS requires: 1) better provision of information about depression for people with MS through healthcare services and community organisations; 2) regular screening and assessment; 3) better healthcare services collaboration to improve management.

Detection of multiple sclerosis lesions in the cervical cord: which of the MAGNIMS 'mandatory' non-gadolinium enhanced sagittal sequences is optimal at 3T?

BACKGROUND AND PURPOSE: The magnetic resonance imaging in multiple sclerosis consensus guidelines currently mandate three sagittal non-contrast enhanced sequences of T2-weighted fast spin echo, proton density-weighted fast spin echo and short tau inversion recovery; however, these particular three sequences have not previously been compared at 3T. This study compared T2-weighted fast spin echo, proton density-weighted fast spin echo, short tau inversion recovery as well as the double inversion recovery sequence for the sagittal detection of multiple sclerosis lesions in the cervical spinal cord at 3T. METHODS: Nineteen multiple sclerosis patients underwent magnetic resonance imaging with 3T sagittal T2-weighted fast spin echo, proton density-weighted fast spin echo, short tau inversion recovery and double inversion recovery between November 2012 and April 2013. Two neuroradiologists independently reviewed the images, and the number of lesions detected on each sequence was recorded. Lesion conspicuity was quantitatively assessed with the lesion-to-cord-contrast ratio and lesion contrast-to-noise ratio. The Wilcoxon signed rank test was performed for statistical analysis. RESULTS: Proton density-weighted fast spin echo and short tau inversion recovery detected 32% more lesions compared to T2-weighted fast spin echo, and 37% more lesions compared to double inversion recovery. The lesion-to-cord-contrast ratio was highest in short tau inversion recovery, while the lesion contrast-to-noise ratio was highest for proton density-weighted fast spin echo. CONCLUSIONS: This study provides the necessary evidentiary support at 3T for the magnetic resonance imaging in multiple sclerosis spinal magnetic resonance imaging protocol consensus guidelines. At 3T sagittal proton density-weighted fast spin echo and short tau inversion recovery sequences allowed improved detection of cervical spinal cord multiple sclerosis lesions, compared to T2-weighted fast spin echo and three-dimensional double inversion recovery magnetic resonance imaging. Utilising T2-weighted fast spin echo alone at 3T is insufficient for lesion detection.

Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats.

Psidium guajava is an important plant of high medicinal value and has been used in traditional systems of medicine against various ailments. The antidiabetic effect of the ethanolic extract of Psidium guajava leaves and also its protective effect on altered glucose metabolism was evaluated in streptozotocin (stz)-induced diabetic rat model. Diabetes was induced in rats by means of intraperitoneal injection of 50-mg/kg body weight (b.wt.) of stz. Diabetes-induced rats were randomly divided into two groups. One group of rats was treated with Psidium guajava leaf extract at a dosage of 300-mg/kg b.wt. and the other group of rats was treated with the standard drug glyclazide at a dosage of 5-mg/kg b.wt. for 30 days. The blood glucose levels, plasma insulin, Hb, HbA1c were measured. The effect on the drug on altered glucose metabolizing enzymes were also studied. Treatment with Psidium guajava extract showed a significant reduction in blood glucose and HbA1c levels and a significant increase in plasma insulin levels. The drug also significantly restored the activities of carbohydrate metabolizing enzymes. This suggests that the potential antidiabetic effect of the ethanolic extract of the Psidium guajava leaves may be due to the presence of flavonoids and other phenolic components present in the drug.

How good are we at diagnosing seizures based on semiology?

The accuracy of visual diagnosis of seizures based on semiologic features among different health care professionals is largely unknown. We evaluated the ability of health care professionals to correctly diagnose epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) from a random selection of 10 ES and 10 PNES videos. The 20 videos (without accompanying electroencephalography) were shown only once, in a random mix to different groups of health care professionals. These individuals, blinded to the diagnosis, were asked to classify the seizure as ES or PNES. We used summary receiver operating characteristic (SROC) curves to determine the accuracy for each group. Next we calculated the difference between the area under the curve (AUC) of SROC between neurologists (as the reference) and the other groups of health care professionals. Neurologists achieved significantly higher AUC results compared to other health care professionals. These results indicate a wide range of diagnostic accuracy among different health care professionals and have practical implications for the evaluation of patients with seizure disorders in acute settings.