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Guanidinoacetic acid (GAA) is the direct precursor to creatine, which serves as an energy reserve mechanism in the body. We evaluated the effects of GAA supplementation on the growth performance of calves fed milk replacer. Forty-five Holstein-Angus steer calves (40.9 kg, approximately 1 week old) were assigned to 1 of 3 treatments to assess growth performance and data from 41 calves were analyzed. Treatments were provided in the milk replacer for 42 d and included 0, 1, or 2 g GAA/d. Calves were fed 2.84 L milk replacer twice daily with ad libitum access to starter feed and water. Treatments ended on day 42 prior to a 17-day weaning period. Supplementation of GAA increased ( p < 0.01) plasma concentrations of GAA (0.42, 0.51, and 0.67 mg/L for 0, 1, and 2 g GAA/d, respectively) and creatine (18.7, 22.1, and 24.4 mg/L for 0, 1, and 2 g GAA/d, respectively). Bodyweight tended to linearly increase ( p = 0.09) with increasing GAA on d 59 (91.2, 98.3, and 98.6 kg for 0, 1, and 2 g GAA/d, respectively). Daily gains from day 0 to 59 tended to increase with GAA provision ( p = 0.09; 0.86, 0.97, and 0.98 kg/d for 0, 1, and 2 g GAA/d, respectively). Starter feed dry matter intake tended to linearly increase ( p = 0.06) with GAA supplementation (0.201, 0.278, and 0.286 kg/d for 0, 1, and 2 g GAA/d, respectively). Treatments providing 1 and 2 g GAA/d affected performance similarly. No differences among treatments were observed for health (respiratory and fecal) scores during the application of treatments or during the subsequent weaning period. The inclusion of GAA in milk replacer tended to increase the gain of calves, and this was associated with elevated starter feed intake.

Rhino orbital Mucormycosis caused by filamentous fungus of mucoraceae family was considered a rare disease affecting immunocompromised and diabetics with ketoacidosis until the recent COVID 19 pandemic. We are presenting a series of six cases of Rhino orbital cerebral Mucormycosis with central retinal artery occlusion. All six cases had common history of COVID 19 infection in recent past with sinusitis, proptosis and total ophthalmoplegia with central retinal artery occlusion on presentation. MR imaging showed invasive pan sinusitis with orbital and cerebral involvement. Urgent debridement was done and histopathological examination showed broad, filamentous aseptate fungi suggestive of Mucormycosis. All patients inspite of intravenous Amphotericin B with local debridement did not show any improvement and expired within a week of presentation. Hence our study shows poor prognosis of post covid 19 associated Mucormycosis with central retinal artery occlusion., Competing Interests: None

The mTORC2 pathway plays a critical role in promoting tumor progression in human colorectal cancer (CRC). The regulatory mechanisms for this signaling pathway are only partially understood. We previously identified UBXN2A as a novel tumor suppressor protein in CRCs and hypothesized that UBXN2A suppresses the mTORC2 pathway, thereby inhibiting CRC growth and metastasis. We first used murine models to show that haploinsufficiency of UBXN2A significantly increases colon tumorigenesis. Induction of UBXN2A reduces AKT phosphorylation downstream of the mTORC2 pathway, which is essential for a plethora of cellular processes, including cell migration. Meanwhile, mTORC1 activities remain unchanged in the presence of UBXN2A. Mechanistic studies revealed that UBXN2A targets Rictor protein, a key component of the mTORC2 complex, for 26S proteasomal degradation. A set of genetic, pharmacological, and rescue experiments showed that UBXN2A regulates cell proliferation, apoptosis, migration, and colon cancer stem cells (CSCs) in CRC. CRC patients with a high level of UBXN2A have significantly better survival, and high-grade CRC tissues exhibit decreased UBXN2A protein expression. A high level of UBXN2A in patient-derived xenografts and tumor organoids decreases Rictor protein and suppresses the mTORC2 pathway. These findings provide new insights into the functions of an ubiquitin-like protein by inhibiting a dominant oncogenic pathway in CRC., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

This study is focused on the selective delivery and release of the plant-based anticancer compound eugenol (EUG) in colorectal cancer cells (CRC). EUG is an apoptotic and anti-growth compound in diverse malignant tumors, including CRC. However, EUG's rapid metabolization, excretion, and side effects on normal cells at higher dosages are major limitations of its therapeutic potential. To address this problem, we developed a "smart" enzyme-responsive nanoparticle (eNP) loaded with EUG that exposes tumors to a high level of the drug while keeping its concentration low among healthy cells. We demonstrated that EUG induces apoptosis in CRC cells irrespective of their grades in a dose- and time-dependent manner. EUG significantly decreases cancer cell migration, invasion, and the population of colon cancer stem cells, which are key players in tumor metastasis and drug resistance. The "smart" eNPs-EUG show a high affinity to cancer cells with rapid internalization with no affinity toward normal colon epithelial cells. NPs-EUG enhanced the therapeutic efficacy of EUG measured by a cell viability assay and showed no toxicity effect on normal cells. The development of eNPs-EUG is a promising strategy for innovative anti-metastatic therapeutics., Competing Interests: The authors declare no conflict of interest.

Purpose: To compare the efficacy and safety of sub-tenon block to peribulbar block with respect to analgesia, akinesia, and complications., Methods: It is an observational study conducted at a government hospital in Karnataka. Seventy patients who came to the ophthalmology OPD for small-incision cataract surgery (SICS) under local anesthesia were included in the study. The participants were divided into two groups of 35 as per the surgeon. The pain was evaluated at the time of administration of the block, during the surgery, and during the postoperative period of 4 h. Akinesia was noted in both the groups and the time of onset of akinesia was noted. Any complications associated with the block such as chemosis or subconjunctival hemorrhage were also noted. Statistical analysis was done using PSS version 25.0, where P &lt; 0.05 was considered significant., Results: The baseline pain score was higher in the peribulbar group (1.57). The onset of akinesia was faster in sub-tenons (90.34 s). Complete akinesia was achieved in 82.9% of patients after peribulbar block. There was no significant difference in complications in both groups., Conclusion: Sub-tenons block is an effective and safer technique of ocular anesthesia for SICS. It can be considered as an alternative to the conventional peribulbar block for SICS., Competing Interests: None

Colorectal cancer (CRC) is one of the most widely diagnosed cancers worldwide. Despite notable improvements in therapeutic strategies available to CRC patients, late stages of CRC have a higher incidence rate of drug resistance, which is associated with a higher mortality rate. The development of therapeutic strategies that use nanoparticles as a drug delivery system has become one of the most promising potential approaches for cancer therapy. Previous studies have shown that a natural plant alkaloid, veratridine (VTD), suppresses colon cancer cell migration and invasion, two essential factors in tumor metastasis, through activation of the gene that encodes the tumor-suppressor protein UBXN2A. The goal of this study is to develop a nanoassembly to selectively deliver VTD to cancer cells and release it on demand while leaving normal cells intact. We packaged the targeted therapy anticancer molecule VTD inside mesoporous silica nanoparticles (MSNs) impermeable to the blood-brain barrier (BBB) and with selective affinity to CRC cells and sealed the VTD-loaded nanoparticles with an enzymatically cleavable protein. The particles will deliver and release VTD only at the targeted colorectal tumor sites. Since the enzyme MMP-7 protease is dominantly secreted by CRC cells, the release triggered by the enzymes will increase VTD concentration at tumor cells, enhancing the efficiency of the new therapy. We have proven the selective affinity of two types of VTD-carrying particles to CRC cells and enzyme- or acid-triggered VTD release. Negatively surface-charged MSNs showed significant affinity toward positively charged cancer cells but not negatively charged normal fibroblast colon cells, making VTD-MSNs a promising anticancer drug with minimal side effects.

Purpose: Stroke can cause physical and emotional problems affecting sexual well-being; healthcare professionals (HCPs) are often uncomfortable discussing this topic with patients. We explored the perspectives of HCPs and stroke survivors about barriers to discussing sexual well-being poststroke., Design: A mixed methodology was employed., Methods: A postal survey of stroke survivors (n = 50), a focus group with HCPs on a stroke unit (n = 6), and a focus group with community-living stroke survivors (n = 6) were used in this study. Focus group data were analyzed thematically., Findings: No patient surveyed (60% response rate) had discussed sexual well-being with an HCP. Focus groups revealed barriers on multiple levels: structural, HCP, patient, and professional-patient interface., Conclusions: Healthcare professionals were poorly trained, adopted a passive role, and addressed sexual activity based on individual beliefs rather than having an agreed team approach., Clinical Relevance: Relatively simple steps like inclusion in policy, training to empower HCPs, and the provision of written information for patients could help to improve practice.