Omega-3 polyunsaturated fatty acid derived lipid mediators: a comprehensive update on their application in anti-cancer drug discovery.

INTRODUCTION: ω-3 Polyunsaturated fatty acids (PUFAs) have a range of health benefits, including anticancer activity, and are converted to lipid mediators that could be adapted into pharmacological strategies. However, the stability of these mediators must be improved, and they may require formulation to achieve optimal tissue concentrations. AREAS COVERED: Herein, the author reviews the literature around chemical stabilization and formulation of ω-3 PUFA mediators and their application in anticancer drug discovery. EXPERT OPINION: Aryl-urea bioisosteres of ω-3 PUFA epoxides that killed cancer cells targeted the mitochondrion by a novel dual mechanism: as protonophoric uncouplers and as inhibitors of electron transport complex III that activated ER-stress and disrupted mitochondrial integrity. In contrast, aryl-ureas that contain electron-donating substituents prevented cancer cell migration. Thus, aryl-ureas represent a novel class of agents with tunable anticancer properties. Stabilized analogues of other ω-3 PUFA-derived mediators could also be adapted into anticancer strategies. Indeed, a cocktail of agents that simultaneously promote cell killing, inhibit metastasis and angiogenesis, and that attenuate the pro-inflammatory microenvironment is a novel future anticancer strategy. Such regimen may enhance anticancer drug efficacy, minimize the development of anticancer drug resistance and enhance outcomes.

Alkindi Sprinkle for Pediatric Patients With Primary Adrenocortical Insufficiency: A Narrative Review.

Adrenocortical insufficiency, also known as adrenal insufficiency (AI), is an endocrine disorder characterized by inadequate production of adrenal hormones, including glucocorticoids and mineralocorticoids (MCs). The condition can be categorized as primary, secondary, or tertiary AI, depending on the location of the defect. Classical symptoms of AI include weakness, fatigue, abdominal pain, tachycardia, hypotension, electrolyte imbalances, and hyperpigmentation. In children, the most common cause of AI is classical congenital adrenal hyperplasia, which results from a deficiency in the 21-hydroxylase enzyme. The 21-hydroxylase enzyme produces all steroids, such as cortisol and aldosterone. AI management primarily involves hormone replacement therapy, typically with oral hydrocortisone and MC supplementation. However, the administration of hydrocortisone to pediatric patients presents challenges related to the lack of available dose-appropriate formulations. Historically, crushed or split adult tablets were used for the pediatric treatment of AI, although this poses an increased risk of under- or overtreatment. Inadequate dosing in the pediatric population can adversely affect growth, development, and metabolic health. Alkindi Sprinkle is a pediatric-specific hydrocortisone oral granule preparation that manages cortisol levels to help facilitate accurate therapeutic dosing. Alkindi offers several advantages, including accurate dosing, taste masking, and ease of administration. The present investigation describes AI, the management of AI, and the treatment of pediatric AI using Alkindi Sprinkle, including clinical efficacy.

Health-related quality of life for pediatric patients with end-stage kidney disease: A systematic review and meta-analysis of the Pediatric Quality of Life Inventory (PedsQL).

INTRODUCTION: Health-related quality of life (HRQoL) studies demonstrate the impact of end-stage renal disease (ESRD) on the physical and psychosocial development of children. While several instruments are used to measure HRQoL, few have standardized domains specific to pediatric ESRD. This review examines current evidence on self and proxy-reported HRQoL among pediatric patients with ESRD, based on the Pediatric Quality of Life Inventory (PedsQL) questionnaires. METHODS: Following PRISMA guidelines, we conducted a systematic review and meta-analysis on HRQoL using the PedsQL 4.0 Generic Core Scale (GCS) and the PedsQL 3.0 ESRD Module among 5- to 18-year-old patients. We queried PubMed, Embase, Web of Science, CINAHL, and Cochrane databases. Retrospective, case-controlled, and cross-sectional studies using PedsQL were included. FINDINGS: Of 435 identified studies, 14 met inclusion criteria administered in several countries. Meta-analysis demonstrated a significantly higher total HRQoL for healthy patients over those with ESRD (SMD:1.44 [95% CI: 0.78-2.09]) across all dimensional scores. In addition, kidney transplant patients reported a significantly higher HRQoL than those on dialysis (PedsQL GCS, SMD: 0.33 [95% CI: 0.14-0.53]) and (PedsQL ESRD, SMD: 0.65 [95% CI: 0.39-0.90]) concordant with parent-proxy reports. DISCUSSION: Patients with ESRD reported lower HRQoL in physical and psychosocial domains compared with healthy controls, while transplant and peritoneal dialysis patients reported better HRQoL than those on hemodialysis. This analysis demonstrates the need to identify dimensions of impaired functioning and produce congruent clinical interventions. Further research on the impact of individual comorbidities in HRQoL is necessary for developing comprehensive, integrated, and holistic treatment programs.

Frailty of Prostate Cancer Patients Receiving Androgen Deprivation Therapy: A Scoping Review.

PURPOSE: This study aimed to explore the existing literature on frailty experienced by patients with prostate cancer (PC) receiving androgen deprivation therapy (ADT). MATERIALS AND METHODS: Database and manual searches were conducted to identify relevant studies published in English, with no limitation on the year of publication, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. Four databases-PubMed, Cochrane Library, EMBASE, and CINAHL-were used for database searches and reference lists, related journals, and Google Scholar were used for manual searches. RESULTS: A total of 12 studies were analyzed for this scoping review. Of these, only 2 were intervention studies, and 1 was a randomized controlled trial. Among the two intervention studies, the multidisciplinary intervention program, including psychological counseling, nutritional coaching, and supervised group physical exercise did not show significant improvement in frailty. In contrast, high-dose vitamin D supplementation significantly decreased frailty. The conceptual and operational definitions of frailty used in each study varied, and the most used one was mainly focused on physical functions. As a result of analyzing the other health-related variables associated with frailty in patients with PC receiving ADT, age, metastases, comorbidities, and incident falls were related to a high frailty level. As for the physiological index, high levels of C-reactive protein, and interleukin-6, and fibrinogen, low levels of total testosterone, lymphocyte count, and creatinine were associated with a high level of frailty. A few studies explored the relationship between psychological and cognitive variables and frailty. CONCLUSIONS: Further research related to frailty in patients with PC receiving ADT should be conducted, and effective interventions to manage frailty should be developed. Additionally, research that considers not only the physical domain of frailty but also the psychological, cognitive, and social domains needs to be conducted.

Transcatheter treatment of the tricuspid valve: current status and perspectives.

Transcatheter tricuspid valve interventions (TTVI) are emerging as alternatives to surgery in high-risk patients with isolated or concomitant tricuspid regurgitation. The development of new minimally invasive solutions potentially more adapted to this largely undertreated population of patients, has fuelled the interest for the tricuspid valve. Growing evidence and new concepts have contributed to revise obsolete and misleading perceptions around the right side of the heart. New definitions, classifications, and a better understanding of the disease pathophysiology and phenotypes, as well as their associated patient journeys have profoundly and durably changed the landscape of tricuspid disease. A number of registries and a recent randomized controlled pivotal trial provide preliminary guidance for decision-making. TTVI seem to be very safe and effective in selected patients, although clinical benefits beyond improved quality of life remain to be demonstrated. Even if more efforts are needed, increased disease awareness is gaining momentum in the community and supports the establishment of dedicated expert valve centres. This review is summarizing the achievements in the field and provides perspectives for a less invasive management of a no-more-forgotten disease.

Enhancing cotton sustainability: Multi-factorial intercropping, irrigation, and weed effects on productivity, quality and physiology.

Drought stress and weed infestation are significant factors that significantly decrease cotton yield. Increasing the variety of plants within a cotton field ecosystem can strengthen its stability and protect it from susceptibility to both biotic and abiotic pressures. In this two-year experiment (2021 and 2022), the effects of intercropping systems (four growth conditions including mono- and inter-cropped cotton varieties Golestan and Hekmat with Nepeta crispa and dragon's head (Lallemantia iberica)), irrigation (three intervals of 3, 6, and 9 days), and weed competition (weed-free and weedy plots) on the agronomic performance, physiological characteristics, and seed quality of cotton in a semi-arid region of Iran were studied. In 2021, the volume of irrigation water applied was 9873, 6100, and 4650 m3 ha-1 for irrigation intervals of 3, 6, and 9 days, respectively. In 2022, the volumes were 9071, 5605, and 4272 m3 ha-1 for the corresponding irrigation intervals. Over two years, Xanthium strumarium, Amaranthus retroflexus, and Portulaca oleracea were the dominant weed species. Weeds had the most significant impact on total dry weight; weed control increased plant vigor and growth, ranging from 1.4 to 2.3 times, while weed impact on cottonseed yield ranged from 18% to 96% reduction. Increasing irrigation intervals resulted in reductions in various parameters, with decreases of 39%-80% in total dry weight, 34%-57% in cottonseed yield, and 48%-72% in lint yield. The harvest indices for seed cotton, cottonseed, and lint ranged from 35.3% to 56.5%, 18.3%-35.0%, and 15.4%-20.5%, respectively. Weeds were responsible for a 17% decrease in the 1000-seed weight. As the irrigation intervals increased from 3 days to 6 days and 9 days, the number of bolls per plant decreased by 19%-85%. Extending the irrigation interval from 3 days to 6 days and 9 days resulted in a substantial decrease in the photosynthetic rate, ranging from 42% to 92%. Mono-cropped Golestan performed well under unstressed conditions such as 3-day interval irrigation and weed-free conditions. On the other hand, intercropped Hekmat demonstrated better resilience to both moisture and weed stresses. The LER (Land equivalent ratio) indices of both intercropping systems were generally favorable, indicating higher productivity compared to sole cropping. The intercropping systems consistently showed the highest LER indices under weedy conditions, highlighting the significance of intercropping as a valuable method in integrated weed management.

High rates of vitamin D insufficiency among patients presenting for total knee arthroplasty.

Widely varying prevalence of vitamin D deficiency has been reported in patients presenting for total knee arthroplasty (TKA). The primary aim of this study was to determine vitamin D levels in TKA patients and to compare to patients already routinely evaluated for vitamin D levels, patients with fragility fractures of the distal radius (DRF). There is significant overlap between patients presenting for TKA and with DRF, both in terms of medical comorbidities and overall health status, making these populations suitable comparative cohorts. Wefound that all patients presenting for TKA consultation had vitamin D insufficiency and 33% had vitamin D deficiency, compared to only 37% and 14% in the DRF cohort, a patient population routinely evaluated for vitamin D due to the high risk of deficiency. Furthermore, patients with DRF had higher levels of vitamin D before (38 ± 16 vs. 23 ± 5) and after vitamin D supplementation (39 ± 17 vs. 33 ± 10), suggesting that patients presenting for TKA are at even higher risk of vitamin D insufficiency than patients presenting with DRF. Reassuringly, supplementation successfully corrected 39.0% and 55.8% of patients in the DRF and TKA cohorts, respectively.

Beyond the joint: Exploring the interplay between mental health and shoulder arthroplasty outcomes.

Considering the fact that mental health illnesses increase with age, and that shoulder arthroplasty procedures are often indicated in the older population, exploring the relationship between mental health and shoulder arthroplasty outcomes can have pivotal implications for shoulder surgeons and patients worldwide. The literature has shown that patients with poor mental health report lower patient-reported outcomes, higher peri-operative complications (such as anemia, infection, delirium, and others), lengthier hospital stays, and higher readmission rates than the normal patient. Employing a holistic approach when managing shoulder arthroplasty patients is necessary for optimizing outcomes and setting up recovery expectations.

Mineralogy and mineral chemistry of the ABM replacement-style volcanogenic massive sulfide deposit, Finlayson Lake district, Yukon, Canada.

The ABM deposit is a bimodal-felsic, replacement-style volcanogenic massive sulfide deposit (VMS) that is hosted by back-arc affinity rocks of the Yukon-Tanana terrane in the Finlayson Lake VMS district, Yukon, Canada. Massive sulfide zones occur as stacked and stratabound lenses subparallel to the volcanic stratigraphy, surrounded by pervasive white mica and/or chlorite alteration. Remnant clasts of volcanic rocks and preserved bedding occur locally within the massive sulfide lenses and indicate that mineralization formed through subseafloor replacement of pre-existing strata. Three mineral assemblages occur at the ABM deposit: (1) a pyrite-chalcopyrite-magnetite-pyrrhotite assemblage that is associated with Cu-Bi-Se-Co-enrichment and occurs at the center of the massive sulfide lenses; (2) a pyrite-sphalerite assemblage, which occurs more commonly towards lens margins and is enriched in Zn-Pb-Ag-Au-Hg-As-Sb-Ba; and (3) a minor assemblage comprising chalcopyrite-pyrrhotite-pyrite stringers associated with pervasive chlorite alteration, which occurs mostly at the sulfide lens margins. Petrographic observations of preserved primary, zone refining, and metamorphic textures in combination with in situ geochemistry show that the pyrite-sphalerite assemblage formed at lower temperatures (< 270 °C) than the other two mineral assemblages (~ 270-350 °C), and that mineral chemistry in all mineral assemblages was affected by greenschist facies metamorphism, although the effects are limited to recrystallization, small-scale remobilization (< 1 m) and trace element redistribution. Supplementary Information: The online version contains supplementary material available at 10.1007/s00126-023-01217-4.

Maternal Fatigue after Postpartum Anemia Treatment with Intravenous Ferric Carboxymaltose vs. Intravenous Ferric Derisomaltose vs. Oral Ferrous Sulphate: A Randomized Controlled Trial.

(1) Background: Postpartum anemia is a common maternal complication and is recognized as a cause of impaired quality of life, reduced cognitive abilities, and fatigue. Efficient iron supplementation for the treatment of postpartum anemia is an essential component of high-quality maternal care. The optimal mode of iron supplementation has not been determined yet, whether oral or intravenous. The objective of this study was to compare postpartum anemia treatment with intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulfate. (2) Methods: A single-center, open-label, randomized controlled trial. Women with hemoglobin < 100 g/L within 48 h postpartum were randomly allocated to receive intravenous ferric carboxymaltose, intravenous ferric derisomaltose, or oral ferrous sulfate. Intravenous iron was given in one or two doses, while ferrous sulfate was given as two 80 mg tablets once daily. The primary outcome was maternal fatigue measured by the Multidimensional Fatigue Inventory (MFI) six weeks postpartum. Hemoglobin, ferritin, and transferrin saturation levels were analyzed as secondary outcomes. A Kruskal-Wallis test was used for group comparison (p < 0.05 significant). (3) Results: Three hundred women were included. The MFI score at six weeks postpartum did not differ between groups (median 38 (inter-quartile range (IQR) 29-47) in the ferric carboxymaltose group, median 34 (IQR 26-42) in the ferric derisomaltose group, and median 36 (IQR 25-47) in the ferrous sulfate group; p = 0.26). Participants receiving oral iron had lower levels of hemoglobin (135 (131-139) vs. 134 (129-139) vs. 131 (125-137) g/L; p = 0.008), ferritin (273 (198-377) vs. 187 (155-246) vs. 24 (17-37) µg/L; p < 0.001) and transferrin saturation (34 (28-38) vs. 30 (23-37) vs. 24 (17-37) %; p < 0.001) than those receiving ferric carboxymaltose or ferric derisomaltose. (4) Conclusions: Intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulfate had similar impacts on maternal fatigue at six weeks postpartum despite improved laboratory parameters in the intravenous groups.

Severe Acute Kidney Injury in Hospitalized Cancer Patients: Epidemiology and Predictive Model of Renal Replacement Therapy and In-Hospital Mortality.

BACKGROUND: Acute kidney injury (AKI) is a common complication among cancer patients, often leading to longer hospital stays, discontinuation of cancer treatment, and a poor prognosis. This study aims to provide insight into the incidence of severe AKI in this population and identify the risk factors associated with renal replacement therapy (RRT) and in-hospital mortality. METHODS: This retrospective cohort study included 3201 patients with cancer and severe AKI admitted to a Comprehensive Cancer Center between January 1995 and July 2023. Severe AKI was defined according to the KDIGO guidelines as grade ≥ 2 AKI with nephrological in-hospital follow-up. Data were analyzed in two timelines: Period A (1995-2010) and Period B (2011-2023). RESULTS: A total of 3201 patients (1% of all hospitalized cases) were included, with a mean age of 62.5 ± 17.2 years. Solid tumors represented 75% of all neoplasms, showing an increasing tendency, while hematological cancer decreased. Obstructive AKI declined, whereas the incidence of sepsis-associated, prerenal, and drug-induced AKI increased. Overall, 20% of patients required RRT, and 26.4% died during hospitalization. A predictive model for RRT (AUC 0.833 [95% CI 0.817-0.848]) identified sepsis and hematological cancer as risk factors and prerenal and obstructive AKI as protective factors. A similar model for overall in-hospital mortality (AUC 0.731 [95% CI 0.71-0.752]) revealed invasive mechanical ventilation (IMV), sepsis, and RRT as risk factors and obstructive AKI as a protective factor. The model for hemato-oncological patients' mortality (AUC 0.832 [95% CI 0.803-0.861]) included IMV, sepsis, hematopoietic stem cell transplantation, and drug-induced AKI. Mortality risk point score models were derived from these analyses. CONCLUSIONS: This study addresses the demographic and clinical features of cancer patients with severe AKI. The development of predictive models for RRT and in-hospital mortality, along with risk point scores, may play a role in the management of this population.

A case of pseudo-Bartter/Gitelman syndrome caused by long-term laxative abuse, leading to end-stage kidney disease.

Pseudo-Bartter/Gitelman syndrome (PBS/PGS) is a disorder that presents with hypokalemia and metabolic alkalosis resembling Gitelman syndrome (GS) due to secondary factors, such as lifestyle and /or medicines. Notably, PBS/PGS is more likely to cause renal dysfunction than GS. We report the first case of PBS/PGS due to long-term laxative abuse leading to end-stage kidney disease (ESKD). The patient was a 49-year-old woman with a history of constipation since school, who had used excessive doses of laxatives on her own judgment for nine years at least from 22 years of age. Two years later, blood tests revealed hypokalemia (serum K 3.1 mEq/L), and nine years later, the patient's renal function began to deteriorate (Cr-eGFR 48.7 mL/min/1.73 m2). Since abuse of laxatives was suspected as the cause, it was changed to the proper dosage of laxatives. At 33 years, the patient developed acute kidney injury (AKI), due to a urinary tract infection, and required intensive treatment, including hemodialysis. Although the patient was eventually weaned off dialysis, the renal function did not recover to pre-AKI levels. In suspected GS, comprehensive genetic testing for renal disease-related genes was performed; however, no obvious pathogenic variants were identified. Thereafter, despite decreasing the laxative doses and potassium supplementation, her renal function continued to decline. At 49 years, the patient developed ESKD and was started on maintenance hemodialysis. PBS/PGS is a disease that can lead to ESKD. An early diagnosis of PBS/PGS is crucial to prevent renal function deterioration, and the underlying causes should be removed immediately.

Effects of manual lymphatic drainage on total knee replacement: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Total knee joint replacement (TKR) is an effective method for the treatment of severe knee osteoarthritis. With an increasing number of surgeries, complications such as lower limb edema, pain, and limited mobility have caused a heavy burden. Manual lymphatic drainage (MLD) may be a solution to solve the problem. The study aims to evaluate the efficacy of MLD in reducing knee edema, pain, and improving range of motion (ROM) in patients after TKR. METHODS: A search was conducted in PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIPs, WanFang database, and Google Scholar from inception to June 2023. Only randomized controlled trials (RCTs) that compared the effects of MLD and non-MLD (or another physiotherapy) on improving knee edema, pain, and ROM after TKR were included. Stata 16.0 was used for meta-analysis. GRADE was used to assess the quality of evidence. RESULTS: In total, 7 RCTs with 285 patients were identified. There were no significant differences found in the ROM of knee flexion (standardized mean difference (SMD) = 0.03, 95% confidence interval (CI): -0.22, 0.28, P = 0.812) and the ROM of knee extension (SMD= -0.30, 95%CI: -0.64, 0.04, P = 0.084). No differences were observed in the lower extremity circumference after TKR (SMD= -0.09, 95%CI: -0.27, 0.09, P = 0.324). For postoperative pain, there was no significant advantage between the MLD and non-MLD groups (SMD= -0.33, 95%CI: -0.71, 0.04, P = 0.083). CONCLUSIONS: Based on the current evidence from RCTs, manual lymphatic drainage is not recommended for the rehabilitation of patients following total knee replacement.

Ultrashort channel MoSe2transistors with selenium atoms replaced at the interface: first-principles quantum-transport study.

Realizing n- and p-type transition metal dichalcogenide (TMD)-based field-effect transistors for nanoscale complementary metal oxide semiconductor (CMOS) applications remains challenging owing to undesirable contact resistance. Quantumtransport calculations were performed by replacing single-sided Se atoms of TMD near the interface with As or Br atoms to further improve the contact resistance. Here, partial selenium replacement produced a novel interface with a segment of metamaterial MoSeX (Pt/MoSeX/MoSe2; X = As, Br). Such stable metamaterials exhibit semi-metallicity, and the contact resistance can be thus lowered. Our findings provide insights into the potential of MoSe2-based nano-CMOS logic devices.

A Review on Osteoarthritis and its Eradication Approaches: An Update.

Osteoarthritis (OA) is a disease characterized by degeneration of cartilage or wear and tear. OA is a cause of disability and health issues. It is a disease that affects more than 500 million adults annually worldwide, of which India accounts for about 22 to 39% of OA patients. The most common type of osteoarthritis is knee OA. Pathogenesis of OA requires evolution in basic science and clinical research to enhance our understanding of the pathogenesis and as well as different treatment options. It is mainly classified as primary and secondary OA. The treatment for OA can only reduce the symptoms and cannot cure the disease itself, including pharmacological treatment, like non-steroidal anti-inflammatory drugs (NSAIDs), acting on COX1 (cyclooxygenase 1) and COX2 (cyclooxygenase 2) enzymes. Non-pharmacological treatments for OA include exercise like walking, and aerobic exercise, diet, weight loss, hot and cold therapy, as well as electrotherapy, which improves muscle strength and decreases joint pain. Surgical treatment is the last treatment option for OA patients, which includes arthroscopy and joint replacement therapy. Thus, necessary precautions should be taken for joints to be healthy and disease-free.

Effectiveness of sesquiterpene derivatives from Cinnamomum genus in nicotine replacement therapy through blocking acetylcholine nicotinate: a computational analysis.

Cigarette smoking poses various health risks, such as increasing the susceptibility to respiratory infections, contributing to osteoporosis, causing reproductive issues, delaying postoperative recovery, promoting ulcer formation and heightening the risk of diabetes. While many harmful effects of smoking are attributed to other cigarette components, it is nicotine's pharmacological effects that underlie tobacco addiction. Nicotine replacement therapy (NRT) aims to alleviate the urge to smoke and mitigate physiological and psychomotor withdrawal symptoms by delivering nicotine. This study explores the potential of sesquiterpene derivative compounds derived from the Cinnamomum genus using computational techniques. The research incorporates molecular docking analyses, Lipinski's rule of five filtration for drug-likeness, pharmacokinetic and toxicity predictions to assess safety profiles and molecular dynamics (MD) simulations to gauge interaction stability. The findings reveal that all sesquiterpene derivative compounds from the Cinnamomum genus can potentially inhibit nicotinic acetylcholine receptors (nAChRs), particularly nAChRÿ7. However, only abscisic acid exhibit active inhibition, along with suitable drug properties, pharmacokinetics and toxicity profiles. MD studies confirm the stability of interactions between abscisic acid with nAChRÿ7. Consequently, abscisic acid, as sesquiterpene derivatives from the Cinnamomum genus, holds substantial promise for further investigation as nAChRÿ7 inhibitors.Communicated by Ramaswamy H. Sarma.

Integrated Management of an Adult Patient with Mucopolysaccharidosis type IVA: A Case Report with a Six-Year Follow-up.

Mucopolysaccharidosis type IVA (MPS-IVA) is a rare lysosomal storage disease caused by N-acetylglucosamine-6-sulfate-sulfatase enzyme deficiency. MPS-IVA patients show severe extra-skeletal and skeletal manifestations, featured by bone pain and deformities, frailty fractures and early onset osteoporosis. The enzyme replacement therapy (ERT) with elosulfase-α stabilizes the MPS-IVA extra-skeletal manifestations but does not significantly improve MPS-IVA skeletal manifestations. We administered an integrated therapy to an MPS-IVA 41-year-old male patient, composed of zoledronic acid, cholecalciferol and a normocalcemic (calcium intake ≥1 g/day), hyposodic (sodium intake ≤5 g/day), and normocaloric diet (bone-diet), other than ERT. During the six-year follow-up, the patient did not develop any adverse events, obtaining an improvement of bone mineral density and quality of life. Given our results, we propose this integrated treatment (i.e. ERT, zoledronic acid, cholecalciferol, and bone diet) in the management of MPS-IVA adult patients. LEARNING POINTS: Mucopolysaccharidosis type IVA (MPS-IVA) is a genetic, rare, and degenerative spondylo-epiphyso-metaphyseal dysplasia characterized by extra-skeletal and skeletal manifestations. The latter impacts on MPS-IVA patient daily activities, and enzyme replacement therapy has a poor efficacy in improving skeletal involvement.The proposed integrated management with enzyme replacement therapy, zoledronic acid, cholecalciferol and bone diet improve both bone mineral density and the prognosis quoad valetudinem of our MPS-IVA patient.

Probiotic, Paraprobiotic, and Hydrolyzed Yeast Mixture Supplementation Has Comparable Effects to Zinc Oxide in Improving Growth Performance and Ameliorating Post-weaning Diarrhea in Weaned Piglets.

A total of 150 21-day-old weaned piglets [(Yorkshire × Landrace) × Duroc] were randomly assigned to 3 groups (CON, TRT1, TRT2) to evaluate the effects of dietary supplementation of probiotic, paraprobiotic, and hydrolyzed yeast mixture (PPY) on growth performance, nutrient digestibility, fecal bacterial counts, fecal calprotectin contents, and diarrhea rate in a 42-day experiment (phase 1: days 1-14; phase 2: days 15-42). There were 10 replicate pens per treatment with 5 pigs per pen (three gilts and two barrows). Pigs in CON were only provided with a basal diet. Pigs in TRT1 were provided with a basal diet + 3000 mg/kg zinc oxide during phase 1 and a basal diet during phase 2. Pigs in TRT2 were provided with a basal diet + 200 mg/kg probiotic (Saccharomyces cerevisiae boulardii) + 800 mg/kg paraprobiotic (inactivated yeast strains of Saccharomyces cerevisiae and Cyberlindnera jadinii) + 10 g/kg hydrolyzed yeast mixture during phase 1, and a basal diet + 100 mg/kg probiotic + 400 mg/kg paraprobiotic mixture during phase 2. Pigs in TRT1 and TRT2 were significantly heavier at day 14 and 42 than CON pigs. Growth rate during days 1-14, 15-42, and 1-42 and feed efficiency during days 1-14 were similarly affected by treatment while feed efficiency was significantly higher for TRT2 pigs between 15-42 and 1-42 days. Moreover, nitrogen and energy digestibility in both TRT1 and TRT2 were higher than that in CON. During experimental periods, diarrhea rate in TRT1 and TRT2 was lower than that in CON. Therefore, we demonstrated that PPY supplementation had comparable effects as ZnO in improving growth performance and nutrient digestibility as well as ameliorating post-weaning diarrhea in weaned piglets.