BACKGROUND: A series of interesting literature reports acknowledges the notable loss of essential and non-essential amino acids (EAAs and NEAAs) during hemodialysis sessions. These losses may exceed 800 g/year, thus contributing towards accelerating the onset of malnutrition in hemodialysis patients (HD).
OBJECTIVE: A novel tailored amino acid formula for oral administration was developed to replace total amounts of each individual amino acid lost during dialysis diffusive/convective HD strategies, monitoring the effects produced on nutritional and hematological status.
METHODS: A three-month randomized double-blind study was conducted on 30 subjects over the age of 70 years extrapolated from a total population of 86 hemodialysis patients. The 30 patients were randomly assigned to two groups: a treatment group of 15 HD patients (TG) to whom a novel mixture containing 5.4 g of AAs was administered solely on interdialytic days, and a control group of 15 HD patients (CG) who received no amino acid supplementation. The AAs mixture was administered post-dialysis at an extended interval from the end of solute and compartmental rebound to replace AA losses and optimize their role in protein anabolism.
RESULTS: The results obtained highlighted a significant improvement in protein intake g/kg/day (Protein Catabolic Rate, p = 0.014), and increased IgG (p = 0.008) and C3 serum levels (p = 0.003) in the TG group alone. Fat mass losses were initially confirmed by means of bioelectrical impedance analysis (BIA) (p = 0.011) and plicometry (p < 0.001) in the CG group alone, although the main objective was to preserve nutritional status and, particularly, muscle mass. The study was extended to investigate the effects produced on anemia, yielding evidence of continued positive effects three months after the end of the study in the TG group alone based on an increase in Hb levels from 11.2 ± 0.6 to 12.1 ± 0.6 (p = 0.004) associated with a reduced demand for erythropoietin i.v. from 12928 ± 9033 to 9286 ± 5398 U.I/week (p = 0.012) and iron i.v. from 75.9 ± 55 to 71.4 ± 33.4 mg/week (p = 0.045).
CONCLUSIONS: The results obtained following oral administration of this novel tailored AA replacement mixture aimed at reinstating the high AA losses produced during hemodialysis suggest the mixture should be prescribed as a standard procedure to all HD patients.

The effect of diets with various dietary MUFA content and n-6/n-3 ratios, diets 1 (55.33, 1.00), 2 (25.30, 1.00), 3 (55.13, 2.05), 4 (24.92, 2.03), 5 (54.94, 8.06) and 6 (24.91, 8.06) and a control diet with fish oil (FO), diet 7 (33.60, 5.97), was studied on growth and digestive physiology of rainbow trout, Oncorhynchus mykiss. Juveniles, 14.65 g ± 0.17, were fed the experimental diets for eight weeks. Those fish fed diet 1 (55.33, 1.00) had the lowest growth and nutritional indices, while fish fed diet 6 (24.91, 8.06) possessed the highest indices. However, fish fed D7 (33.60, 5.97) was intermediate in this regard. Proximate body composition results revealed no significant differences among various experimental groups (P > 0.05). Fish fed on diet 1 possessed the highest alkaline protease activity, while fish raised on diet 2 showed the lowest enzyme activity (P < 0.05). Fish fed on diets 1, 3 and 4 had the highest lipase activity (P > 0.05). Amylase activity and intestinal parameters did not differ among groups (P > 0.05). MUFA contents of liver and muscle reflected the MUFA contents of the diets; however, liver PUFA contents was not affected by dietary PUFA contents (P < 0.05). However, 18:3n-3 contents of liver decreased as dietary n-6/n-3 ratio increased (P < 0.05). Furthermore, the liver 20:4n-6 contents considerably increased as dietary n-6/n-3 increased to 8.06 (P < 0.05). Muscle 22:6n-3 content of groups 1 to 6 was lower than group 7 (P < 0.05). In conclusion, rainbow trout was considerably capable of de novo synthesis of 22:6n-3. Meanwhile, increasing dietary n-6/n-3 ratio to 8.06 decreased the muscle 22:6n-3 content which requires further considerations regarding fish immune competence and nutritional quality for human consumption.

BACKGROUND: Total shoulder arthroplasty is performed by orthopedic surgeons with various fellowship training backgrounds. Whether surgeons performing shoulder arthroplasty with different types of fellowship training have differing rates of complications and reoperation remains unknown.
METHODS: The PearlDiver Mariner database was retrospectively queried from the years 2010-2022. Patients undergoing shoulder arthroplasty were selected using the CPT code 23472. Those undergoing revision arthroplasty and those with a history of fracture, infection, or malignancy were excluded. Fellowship was determined and verified via online search. Only surgeons who performed a minimum of 10 cases were selected; and PearlDiver was queried using their provider ID codes. Primary outcome measures included 90-day, 1-year, and 5-year rates of complication and reoperation. A Bonferroni correction was utilized in which the significance threshold was set at p≤0.00023 RESULTS: In total, 150,385 patients met the inclusion criteria and were included in the study. Analysis of surgical trends revealed that Sports Medicine and Shoulder and Elbow fellowship- trained surgeons are performing an increasing percentage of all shoulder arthroplasty over time, with each cohort exhibiting am 11.3% and 4.2% increase from 2010 to 2022, respectively. The geographic region with the highest proportion of cases performed by Sports Medicine surgeons was the West, while the Northeast has the highest proportion of cases performed by Shoulder and Elbow surgeons. Shoulder and Elbow surgeons operated on patients that were significantly younger and had fewer comorbidities. Both Shoulder and Elbow and Sports Medicine surgeons had lower rates of postoperative complications at 90 days, 1 year and 5 years in comparison to surgeons who completed another type of fellowship or no fellowship. Across each time point, the rates of individual complications between Sports Medicine and Shoulder and Elbow were comparable, but the pooled complication rate was lowest in the Shoulder and Elbow cohort.
CONCLUSIONS: Surgeons who have completed either a Sports Medicine or Shoulder and Elbow fellowship are performing an increasing proportion of shoulder arthroplasty over time. Sports Medicine and Shoulder and Elbow-trained surgeons have significantly lower complication rates at 90 days, 1 year and 5 years postoperatively. The individual complication rates between Sports Medicine and Shoulder and Elbow are comparable, but Shoulder and Elbow has the lowest pooled complication rates overall.

Microglia are resident immune cells in the central nervous system (CNS) that play vital roles in CNS development, homeostasis and disease pathogenesis. Genetic defects in microglia lead to microglial dysfunction, which in turn leads to neurological disorders. The correction of the specific genetic defects in microglia in these disorders can lead to therapeutic effects. Traditional genetic defect correction approaches are dependent on viral vector-based genetic defect corrections. However, the viruses used in these approaches, including adeno-associated viruses, lentiviruses and retroviruses, do not primarily target microglia; therefore, viral vector-based genetic defect corrections are ineffective in microglia. Microglia replacement is a novel approach to correct microglial genetic defects via replacing microglia of genetic defects with allogenic healthy microglia. In this paper, we systematically review the history, rationale and therapeutic perspectives of microglia replacement, which would be a novel strategy for treating CNS disorders.

UNASSIGNED: Severe acetabular bone defects can pose challenges in revision total hip replacement. The use of structural allografts and various sizes of grain allografts has been proposed as an alternative surgical technique for treating Paprosky type 3 acetabular defects. This study aimed to evaluate the long-term outcomes and potential complications associated with this approach.
UNASSIGNED: A retrospective review was performed on 102 hip reconstructions in patients with major acetabular bone loss, including 81 cases of type 3A and 21 cases of type 3B according to Paprosky\'s classification. Surgical procedures involved the use of structural allografts and various sizes of grain allografts in both reinforcement ring group and cementless cups group.
UNASSIGNED: At a mean follow-up of 82.75 months, 76% of hips had no complications, while The others experienced pain changes in the cup position, post-operative dislocations, and infections. The mean pre-operative Modified Harris Hip Score improved in both groups at the last follow-up.
UNASSIGNED: The use of structural allografts and various sizes of grain allografts for treating type 3 acetabular defects in revision total hip replacement showed promising long-term outcomes and a low rate of complications. Level of Evidence IV; Retrospective Case Series.
UNASSIGNED: Defeitos ósseos acetabulares graves podem representar desafios na revisão da artroplastia total do quadril. O uso de aloenxertos estruturais e aloenxertos de grãos de vários tamanhos foram propostos como uma técnica cirúrgica alternativa para o tratamento de defeitos acetabulares Paprosky tipo 3. O objetivo deste estudo foi avaliar os resultados de longo prazo e as possíveis complicações associadas a essa abordagem.
UNASSIGNED: Foi realizada uma revisão retrospectiva de 102 reconstruções de quadril em pacientes com grande perda óssea acetabular, incluindo 81 casos do tipo 3A e 21 casos do tipo 3B de acordo com a classificação de Paprosky. Os procedimentos cirúrgicos envolveram o uso de aloenxertos estruturais e aloenxertos de grãos de vários tamanhos, tanto no grupo do anel de reforço quanto no grupo das próteses sem cimento.
UNASSIGNED: Em um acompanhamento médio de 82,75 meses, 76% dos quadris não apresentaram complicações, enquanto os demais apresentaram dor, alterações na posição da prótese, luxações pós-operatórias e infecções. A pontuação média pré-operatória do escore de quadril modificado de Harris melhorou em ambos os grupos no último acompanhamento.
UNASSIGNED: O uso de aloenxertos estruturais e aloenxertos de grãos de vários tamanhos para o tratamento de defeitos acetabulares do tipo 3 na substituição total do quadril de revisão mostrou resultados promissores em longo prazo e uma baixa taxa de complicações. Nível de Evidência IV; Série de Casos Retrospectivos.

(1) Background: At present, the only potency assay approved in China for the in-country testing of botulinum toxin type A for injection products is the mouse bioassay (MBA). The Chinese market for neurotoxin products is rapidly expanding, but MBAs are subject to high variability due to individual variations in mice, as well as variations in injection sites, in addition to the limited number of batches tested for one MBA. Compared with the mLD50 method, the cell-based potency assay (CBPA) developed for the potency testing of onabotulinumtoxinA (BOTOX) by AbbVie not only does not use any experimental animals but also allows for significant time and cost savings. Due to the significant benefits conferred by the replacement of the mLD50 assay with CBPA in China, the CBPA method has been transferred, validated, and cross-validated to demonstrate the equivalence of the two potency methods. (2) Methods: The differentiated SiMa cells were treated with both BOTOX samples and the reference standard, and the cleaved SNAP25197 in the cell lysates was quantified using Chemi-ECL ELISA. A 4-PL model was used for the data fit and sample relative potency calculation. The method accuracy, linearity, repeatability, and intermediate precision were determined within the range of 50% to 200% of the labeled claim. A statistical equivalence of the two potency methods (CBPA and mLD50) was initially demonstrated by comparing the AbbVie CBPA data with NIFDC mLD50 data on a total of 167 commercial BOTOX lots (85 50U lots and 82 100U lots). In addition, six lots of onabotulinumtoxinA (three 50U and three 100U) were re-tested as cross-validation by these two methods for equivalence. (3) Results: The overall assay\'s accuracy and intermediate precision were determined as 104% and 9.2%, and the slope, R-square, and Y-intercept for linearity were determined as 1.071, 0.998, and 0.036, respectively. The repeatability was determined as 6.9%. The range with the acceptable criteria of accuracy, linearity, and precision was demonstrated as 50% to 200% of the labeled claim. The 95% equivalence statistic test using margins [80%, 125%] indicates that CBPA and mLD50 methods are equivalent for both BOTOX strengths (i.e., 50U and 100U). The relative potency data from cross-validation were within the range of ≥80% to ≤120%. (4) Conclusions: The CBPA meets all acceptance criteria and is equivalent to mLD50. The replacement of mLD50 with CBPA is well justified in terms of ensuring safety and efficacy, as well as for animal benefits.

Assistance during calving and cesarean section (C-section) are important risk factors for the failure of transfer of passive immunity (FTPI) in beef calves, which increases the risk of morbidity and mortality in beef calves during the preweaning period. Colostrum replacement recommendations for beef calves, and especially for those delivered by C-section, are unavailable. The objective of this study was to determine whether or not colostrum replacement or supplementation with a commercially available product could increase serum IgG concentrations in beef calves delivered by elective C-section, compared to beef calves that nursed colostrum naturally. An elective C-section was performed in 32 pregnant beef cows and first-calf heifers. Immediately after delivery, newborn calves were randomly assigned to one of three different treatment groups. Group A calves (n = 7) were fed one packet of a commercial colostrum replacer (CR) product providing 60 g of IgG within 30 min of life. A second packet of the same CR was fed at 6 h of life. Group B calves (n = 13) were fed the same CR at the same frequency as group A; however, these calves were reunited with their dams after the second CR feeding to allow additional nursing of maternal colostrum. Group C calves (n = 12) were united with their dams immediately after surgery without colostrum intervention. Serum IgG levels at 48 h of life were greater in group C calves and in calves born to multiparous cows. Based on the results of this study, neither colostrum replacement nor supplementation result in higher serum IgG concentrations in beef calves delivered by elective C-section compared with natural nursing.

Periprosthetic fracture following knee arthroplasty is a rare but devastating complication associated with significant morbidity. With unicompartmental knee arthroplasty being performed far less frequently than total knee arthroplasty, periprosthetic fracture following unicompartmental knee arthroplasty presents a particular challenge to orthopaedic surgeons, due to clinical unfamiliarity and sparsity of literature. An up-to-date review of the epidemiology, risk factors, and management strategies for PPF after UKA is presented.

BACKGROUND: Tracheoesophageal speech is one of the most effective method used for voice rehabilitation after laryngectomy. The main limitation is the need for periodic voice prothesis (VP) replacements. The process of developing VP usage complications is still unexplored. The aim of this study was to assess the level of cytokines (IL-1β, IL-6, IL-8, IL-10, TNFα) and pepsin in saliva as potential factors reducing VP longevity.
METHODS: Prospective double-blind randomized clinical trial was conducted (NCT04268459). Patients were randomly divided into two groups depending on VP replacement regimen (regular-every 3 months, or irregular-when complications occur). Levels of IL-1β, IL-6, IL-8, IL-10, TNFα, and pepsin in saliva samples (fasting and after eating) of laryngectomized patients were measured using ELISA tests.
RESULTS: Fifty-two patients (26 in both groups) with control group (7 patients) participated in the study. The level of IL-1β, IL-6, IL-8, IL-10, TNFα, and pepsin did not differ according to regularity of VP replacements (p = 0.301-0.801). IL-6 levels were significantly higher when VP complications occurs (p = 0.012).
CONCLUSIONS: The saliva components were not significantly different depending on the frequency of VP replacements. IL-6 plays an important role in the development of VP use complications.

Undisturbed home cage recording of mouse activity and behavior has received increasing attention in recent years. In parallel, several technologies have been developed in a bid to automate data collection and interpretation. Thanks to these expanding technologies, massive datasets can be recorded and saved in the long term, providing a wealth of information concerning animal wellbeing, clinical status, baseline activity, and subsequent deviations in case of experimental interventions. Such large datasets can also serve as a long-term reservoir of scientific data that can be reanalyzed and repurposed upon need. In this review, we present how the impact of Big Data deriving from home cage monitoring (HCM) data acquisition, particularly through Digital Ventilated Cages (DVCs), can support the application of the 3Rs by enhancing Refinement, Reduction, and even Replacement of research in animals.