Assessment of fish protein hydrolysate as a substitute for fish meal in white shrimp diets: Impact on growth, immune response, and resistance against Vibrio parahaemolyticus infection.

This study investigated the effects of fish protein hydrolysate derived from barramundi on growth performance, muscle composition, immune response, disease resistance, histology and gene expression in white shrimp (Penaeus vannamei). In vitro studies demonstrated FPH enhanced mRNA expressions of key immune-related genes and stimulated reactive oxygen species (ROS) production and phagocytic activity in shrimp hemocytes. To evaluate the effects of substituting fish meal with FPH in vivo, four isoproteic (43 %), isolipidic (6 %), and isoenergetic diets (489 kcal/100 g) were formulated with fish meal substitution levels of 0 % (control), 30 % (FPH30), 65 % (FPH65), and 100 % (FPH100). After 8-week feeding, the growth performance of FPH65 and FPH100 were significantly lower than that of control and FPH30 (p < 0.05). Similarly, the midgut histological examination revealed the wall thickness and villi height of FPH100 were significantly lower than those of control (p < 0.05). The shrimps were received the challenge of AHPND + Vibrio parahaemolyticus at week 4 and 8. All FPH-fed groups significantly enhanced resistance against Vibrio parahaemolyticus at week 4 (p < 0.05). However, this protective effect diminished after long-period feeding. No significant difference of survival rate was observed among all groups at week 8 (p > 0.05). The expressions of immune-related genes were analyzed at week 4 before and after challenge. In control group, V. parahaemolyticus significantly elevated SOD in hepatopancreas and Muc 19, trypsin, Midline-fas, and GPx in foregut (p < 0.05). Moreover, hepatopancreatic SOD of FPH65 and FPH100 were significantly higher than that of control before challenge (p < 0.05). Immune parameters were measured at week 8. Compared with control, the phagocytic index of FPH 30 was significantly higher (p < 0.05). However, dietary FPH did not alter ROS production, phenoloxidase activity, phagocytic rate, and total hemocyte count (p > 0.05). These findings suggest that FPH30 holds promise as a feed without adverse impacts on growth performance while enhancing the immunological response of white shrimp.

Inter-physician Communication in Pediatric Orthopaedics: What do Pediatricians Want to Hear From us?

BACKGROUND: Pediatric orthopaedic surgeons often communicate with general pediatric providers to facilitate patient care, but little data exist on communication preferences. This study investigates pediatric provider preferences regarding when they would like to receive patient updates from pediatric orthopedists, which communication modalities they prefer, and what information they like to receive. METHODS: We developed a 19-question e-mail survey to evaluate provider preferences on communication modality, timing, frequency, and what data they deem important as it relates to musculoskeletal patient care. RESULTS: A total of 111 general pediatric providers in our geographical region completed the survey. Among the providers, 55.9% preferred fax, 40.5% electronic health record inbox message, 19.8% e-mail, 12.6% mail, and 7.2% call/voicemail. The majority (67.9%) preferred information in a traditional note format, whereas 24.8% preferred a summary in paragraph format. Patient diagnosis and treatment plan for shared patients were the most important pieces of information for general pediatric providers to receive from pediatric orthopedists. Of various patient-specific scenarios included in the survey, referrals for osteomyelitis concern, fractures requiring surgery, scoliosis concern, and developmental dysplasia of the hip requiring treatment were considered most important for pediatric orthopedists to send updates. In terms of frequency of communication, over half of the pediatric providers (59.5%) desired updates after the first visit and after care plan changes (50.5%). CONCLUSION: Only 43.5% of pediatric providers feel like current communication with pediatric orthopaedic surgeons is "always" or "often" adequate. Most of our surveyed providers preferred occasional SOAP notes through fax as communication from pediatric orthopaedic surgeons. The communication deemed most important to providers related to referrals where the provider makes the initial diagnosis and then refers the patient to orthopaedics for a condition with potential long-term patient impacts. Finally, providers felt communication was most important after the first pediatric orthopaedic office visit. EVIDENCE: Level III, survey based.

Medial Patellofemoral Ligament Reconstruction in Adolescents: What Parents Care About.

INTRODUCTION: Numerous techniques exist for pediatric medial patellofemoral ligament (MPFL) reconstruction (MPFL-R). Pediatric orthopaedic surgeons and patient families must navigate choices between allograft and autograft, incision type, and surgery cost. While previous research has found similar surgical outcomes among different MPFL-R techniques, minimal data exists on what patients and their families prefer. To engage in shared decision-making (SDM), pediatric orthopaedic surgeons must understand family preferences, including between incision type and cost. We conducted a study utilizing choice-based conjoint (CBC) analysis to explore these preferences. METHODS: A survey was developed using Sawtooth Software (Lighthouse Studio version 9.2.0) to gather demographic information and preferences on surgical scenarios via CBC analysis. Anonymous participants, recruited via the Prolific crowdsourcing platform, qualified if they were US residents over 18 years of age with children aged 13 to 17. Data analysis involved the Hierarchical Bayes (HB) method to generate utility scores to determine the desirability of attributes. RESULTS: The study included 496 participants who prioritized surgical success (average importance 48.8%) followed by co-pay amount (21.5%), incision size (17.4%), and return to sport (12.3%). Participants earning over $200,000 annually prioritized incision size over cost (25.8% vs. 12.1%, P<0.0053). Those with incomes below $50,000 valued recovery time at a lesser extent than other income groups (10.4% than 12.3% overall importance P<0.0003). The sex of the child significantly influenced preferences: incision size was more important to parents of girls (21.1%) than boys (14.0%, P<.0001). The importance of surgery success and recovery time also differed by sex, being higher for boys (50.4%, 13.1%) than girls (47.0%, 11.7%; P=0.025, 0.026, respectively). CONCLUSIONS: This CBC analysis suggests parents of adolescent patients undergoing MPFL-R most value surgical success (avoiding revision surgery), followed by copay, incision size, and time to return to sport. Of note, parent income level and sex of the child significantly influenced parental preferences. We hope this information will assist orthopaedic surgeons in SDM in MPFL-R surgery. LEVEL OF EVIDENCE: Level III.

Effects of Replacing Fish Meal with Enzymatic Cottonseed Protein on the Growth Performance, Immunity, Antioxidation, and Intestinal Health of Chinese Soft-Shelled Turtle (Pelodiscus sinensis).

The dietary effects of replacing fish meal with enzymatic cottonseed protein (ECP) on the growth performance, immunity, antioxidant, and intestinal health of Chinese soft-shelled turtles have not been explored. An eight-week feeding trial was conducted with a quadruplicated group of turtles (3.44 ± 0.01 g) that were randomly assigned to 16 cages (0.6 m × 0.6 m × 0.6 m) with 30 turtles that were stocked in each cage. Four dietary groups were fed with diets supplemented with 0, 2%, 4%, and 6% (ECP0 group (control group), ECP2 group, ECP4 group, ECP6 group) of enzymatic cottonseed protein replacing fishmeal. The present study illustrated that the final weight and WG in the ECP2 and ECP4 groups were significantly increased (P < 0.05) compared with the control group. The ECP2, ECP4, and ECP6 groups significantly reduced the feed coefficient (P < 0.05) and significantly increased the SGR (P < 0.05). The serum TP and ALB of the ECP4 group were significantly increased (P < 0.05). The ECP2, ECP4, and ECP6 groups significantly increased the activity of intestinal pepsin (P < 0.05), and the activity of intestinal lipase of the EPC4 group was significantly increased (P < 0.05). The intestinal villus height of the EPC4 group and EPC6 group, the villus width of the EPC2 group and EPC4 group, and the intestinal muscle thickness of the EPC4 group were significantly increased (P < 0.05). At the same time, replacing fishmeal with enzymatic cottonseed protein also affected the intestinal inflammation-related genes compared with the control group. Besides that, the expression of the IL-10 gene in the experimental group was significantly upregulated (P < 0.05). Nevertheless, the expression of TNF-α and IL-8 genes in the ECP2 group and TNF-α and IL-1ß genes in the ECP4 group was significantly downregulated (P < 0.05). In summary, replacing fish meal with enzymatic cottonseed protein positively affects the growth, immunity, and intestinal health of Chinese soft-shelled turtles. The appropriate proportion of enzymatic cottonseed protein to replace fish meal in turtle feed is 4%.

Alpha-ketoglutaric acid mitigates the detrimental effects of soy antigenic protein on the intestinal health and growth performance of Mirror carp Cyprinus carpio.

The study investigated the alleviated effects of Alpha-ketoglutaric acid (AKG) on the intestinal health of mirror carp (Cyprinus carpio Songpu) caused by soy antigenic protein. The diets were formulated from fishmeal (CON), 50% soybean meal (SBM), the mixture of glycinin and ß-conglycinin (11 + 7S) and adding 1% AKG in the 11 + 7S (AKG). Carp (~ 4 g) in triplicate (30 fish per tank) was fed to apparent satiation thrice a day for six weeks. Compared with CON, SBM treatment resulted in significantly poor growth performance (P < 0.05), whereas 11 + 7S and AKG treatments were not significantly different from CON (P > 0.05). Gene expression of tumor necrosis factor (TNF-α) and interleukin-1 ß (IL-1ß) in proximal intestines (PI) and distal intestines (DI) were increased (P < 0.05), and transforming growth factor (TGF-ß) in PI and middle intestines (MI) was decreased (P < 0.05) in both SBM and 11 + 7S. The caspase-3 in DI increased in SBM (P < 0.05) and the caspase-3 and caspase-9 in DI increased in 11 + 7S (P < 0.05); conversely, TGF-ß in PI and MI was increased, TNF-α and IL-1ß in the MI, caspase-3, and caspase-9 in DI was decreased in AKG (P < 0.05). The TOR (target of rapamycin) in PI and MI, ACC in PI, MI and DI was decreased in SBM (P < 0.05), the AMPK in the PI and DI, TOR in PI, MI and DI, ACC in PI and DI, 4E-BP in DI was reduced in 11 + 7S (P < 0.05). AMPK in the PI and DI, ACC in the PI and MI, TOR in PI, MI, and DI, 4E-BP in PI and DI was recovered by AKG supplementation (P < 0.05). Lipids and lipid-like metabolism, organic acids and derivatives metabolism increased in AKG dietary treatment. In conclusion, AKG reduces the expression of intestinal inflammation and apoptosis pathway and changes glycerophospholipid metabolism and sphingolipid metabolism in the intestine of fish.

Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA.

Self-amplifying RNA (saRNA) is a cutting-edge platform for both nucleic acid vaccines and therapeutics. saRNA is self-adjuvanting, as it activates types I and III interferon (IFN), which enhances the immunogenicity of RNA vaccines but can also lead to inhibition of translation. In this study, we screened a library of saRNA constructs with cis-encoded innate inhibiting proteins (IIPs) and determined the effect on protein expression and immunogenicity. We observed that the PIV-5 V and Middle East respiratory syndrome coronavirus (MERS-CoV) ORF4a proteins enhance protein expression 100- to 500-fold in vitro in IFN-competent HeLa and MRC5 cells. We found that the MERS-CoV ORF4a protein partially abates dose nonlinearity in vivo, and that ruxolitinib, a potent Janus kinase (JAK)/signal transducer and activator of transcription (STAT) inhibitor, but not the IIPs, enhances protein expression of saRNA in vivo. Both the PIV-5 V and MERS-CoV ORF4a proteins were found to enhance the percentage of resident cells in human skin explants expressing saRNA and completely rescued dose nonlinearity of saRNA. Finally, we observed that the MERS-CoV ORF4a increased the rabies virus (RABV)-specific immunoglobulin G (IgG) titer and neutralization half-maximal inhibitory concentration (IC50) by ∼10-fold in rabbits, but not in mice or rats. These experiments provide a proof of concept that IIPs can be directly encoded into saRNA vectors and effectively abate the nonlinear dose dependency and enhance immunogenicity.

Two Directing Groups Used for Metal Catalysed Meta-C-H Functionalisation Only Effect Ortho Electrophilic C-H Borylation.

Two templates used in meta-directed C-H functionalisation under metal catalysis do not direct meta-C-H borylation under electrophilic borylation conditions. Using BCl3 only Lewis adduct formation with Lewis basic sites in the template is observed. While combining BBr3 and the template containing an amide linker only led to amide directed ortho C-H borylation, with no pyridyl directed meta borylation. The amide directed borylation is selective for the ortho borylation of the aniline derived unit in the template, with no ortho borylation of the phenylacetyl ring - which would also form a six membered boracycle - observed. In the absence of other aromatics amide directed ortho borylation on to phenylacetyl rings can be achieved. The absence of meta-borylation using two templates indicates a higher barrier to pyridyl directed meta borylation relative to amide directed ortho borylation and suggests that bespoke templates for enabling meta-directed electrophilic borylation may be required.

[Minors in a French custody center: Sociodemographic characteristics, global health and vulnerability factors]. / Mineurs en garde à vue: caractéristiques sociodémographiques, auto-évaluation de la santé et identification de facteurs de vulnérabilité.

Minor offenders are at risk for medico-psycho-social vulnerability, that impacts global health, schooling, professional future, and socio-familial environment; moreover, minors who are victims of violence and neglect are at greater risk of becoming offenders and minor offenders are at greater risk of suffering violence. Few data are currently available regarding global health and vulnerability factors for minors (i.e. those aged under 18) who have been placed in police custody. This study aimed to describe the judicial and social characteristics of these minors, their medical and psychological health status, with the hypothesis that most minors placed in police custody can be considered as abused or neglected, by presenting factors of vulnerability. We carried out a prospective study, including consecutive minors aged of 13 to 18 years old, who had been detained in custody at the Central Police Station of Nantes (France), from October 2012 to May 2013. The sociodemographic characteristics, scores for global health and the data collected from the welfare and judiciary services were analyzed, to identify abused or neglected minors. Ninety-nine teenagers were included: 78 males and 11 females (mean age±standard deviation: 16.5 years±1.01), who had been placed in custody for robbery, with a remarkable proportion of recidivist minors. Our study has highlighted several worrying characteristics of minors in police custody reflecting their vulnerability, as living conditions (no schooling, no fixed address) and irregular or absent medical follow-up; however their scores for global health were not different from the general population. While 49 minors (49.5 %) had already been identified by the welfare services, our study find that 35 added minors of this population should nonetheless be considered as being abused and/or neglected, based on a very high rate of minors already followed by child protection services and/or already penalized. Systematic health screening in custody could help to detect abused and/or neglected minors, in order to provide them access to appropriate medical and social cares. They could be referring to psychiatric or rehabilitation cares, and to the relevant welfare and judiciary services in order to assess if a specific protection measure is needed.

Mannosylated Poly(ethylene imine) Copolymers Enhance saRNA Uptake and Expression in Human Skin Explants.

Messenger RNA (mRNA) is a promising platform for both vaccines and therapeutics, and self-amplifying RNA (saRNA) is particularly advantageous, as it enables higher protein expression and dose minimization. Here, we present a delivery platform for targeted delivery of saRNA using mannosylated poly(ethylene imine) (PEI) enabled by the host-guest interaction between cyclodextrin and adamantane. We show that the host-guest complexation does not interfere with the electrostatic interaction with saRNA and observed that increasing the degree of mannosylation inhibited transfection efficiency in vitro, but enhanced the number of cells expressing GFP by 8-fold in human skin explants. Besides, increasing the ratio of glycopolymer to saRNA also enhanced the percentage of transfected cells ex vivo. We identified that these mannosylated PEIs specifically increased protein expression in the epithelial cells resident in human skin in a mannose-dependent manner. This platform is promising for further study of glycosylation of PEI and targeted saRNA delivery.

The In Vitro, Ex Vivo, and In Vivo Effect of Polymer Hydrophobicity on Charge-Reversible Vectors for Self-Amplifying RNA.

RNA technology has the potential to revolutionize vaccination. However, the lack of clear structure-property relationships in relevant biological models mean there is no clear consensus on the chemical motifs necessary to improve RNA delivery. In this work, we describe the synthesis of a series of copolymers based on the self-hydrolyzing charge-reversible polycation poly(dimethylaminoethyl acrylate) (pDMAEA), varying the lipophilicity of the additional co-monomers. All copolymers formed stable polyplexes, showing efficient complexation with model nucleic acids from nitrogen/phosphate (N/P) ratios of N/P = 5, with more hydrophobic complexes exhibiting slower charge reversal and disassembly compared to hydrophilic analogues. The more hydrophobic copolymers outperformed hydrophilic versions, homopolymer controls and the reference standard polymer (polyethylenimine), in transfection assays on 2D cell monolayers, albeit with significantly higher toxicities. Similarly, hydrophobic derivatives displayed up to a 4-fold higher efficacy in terms of the numbers of cells expressing green fluorescent protein (GFP+) cells in ex vivo human skin (10%) compared to free RNA (2%), attributed to transfection enrichment in epithelial cells. In contrast, in a mouse model, we observed the reverse trend in terms of RNA transfection, with no observable protein production in more hydrophobic analogues, whereas hydrophilic copolymers induced the highest transfection in vivo. Overall, our results suggest an important relationship between the vector lipophilicity and RNA transfection in vaccine settings, with polymer biocompatibility potentially a key parameter in effective in vivo protein production.

Efficacy of purified nucleotide supplements on the growth performance and immunity of hybrid striped bass Morone chrysops x Morone saxatilis.

Fishmeal is being increasingly replaced in aquatic animal diets with alternative plant protein feedstuffs such as soybean meal which have lower concentrations of nucleotides; therefore, supplemental sources of exogenous nucleotides in diets could become increasingly important. A 9-week feeding trial was conducted with triplicate groups of juvenile hybrid striped bass (average initial body weight ± standard deviation, 5.6 ± 0.1 g) to determine the effects of supplementing single purified nucleotides on the growth performance and immune parameters. The basal diet, which utilized menhaden fishmeal (25%) and soybean meal (75%) as protein sources, contained 44% protein, 10% lipid and an estimated digestible energy level of 3.5 kcal g-1. Single additions of 5'- adenosine monophosphate (AMP), 5'- uridine monophosphate (UMP), 5'- cytidine monophosphate (CMP), 5'- guanosine monophosphate (GMP), and 5'- inosine monophosphate (IMP) disodium salts (Chem-Impex International, Wood Dale, Illinois, USA) were evaluated with each nucleotide added to the basal diet at 0.5% of dry weight at the expense of cellulose. A positive control diet in this trial was a diet containing 5'- AMP from Sigma-Aldrich also supplemented at 0.5% by weight. Results showed significantly (P < 0.05) improved weight gain between fish fed AMP-supplemented diets and the basal diet. No statistical significance (P > 0.05) was detected in whole-body proximate composition and protein retention of fish fed any of the dietary treatments. The respiratory burst of whole blood phagocytes also was significantly (P < 0.05) higher in fish fed the AMP Sigma diet compared to the other dietary treatments. Dietary IMP and AMP both significantly (P < 0.05) enhanced the capacity of isolated phagocytes to generate extracellular superoxide anion compared to all other dietary treatments. No significant differences were seen in other innate immune parameters such as plasma lysozyme, total plasma protein, and total immunoglobulin. The ability of isolated B lymphocytes to proliferate prompted by the presence of lipopolysaccharides was significantly (P < 0.05) different among dietary treatments with the highest simulation index observed in fish fed the diets containing AMP Sigma and UMP; however, it was not significantly different from that of fish fed the basal diet. Based on all the measured responses, it is concluded that AMP at 0.5% of diet had the most positive influence on growth performance and innate immunostimulation of hybrid striped bass.

Does Very High Surgeon or Hospital Volume Improve Outcomes for Hemiarthroplasty Following Femoral Neck Fractures?

BACKGROUND: This study evaluates whether very high-volume hip arthroplasty providers have lower complication rates than other relatively high-volume providers. METHODS: Hemiarthroplasty patients ≥60 years old were identified in the New York Statewide Planning and Research Cooperative System 2001-2015 dataset. Low-volume hospitals (<50 hip arthroplasty cases/y) and surgeons (<10 cases/y) were excluded. The upper and lower quintiles were compared for the remaining "high-volume" hospitals (50-70 vs >245) and surgeons (10-15 vs ≥60) using multivariable Cox proportional hazards regression. Multiple sensitivity analyses were performed treating volume as a continuous variable. RESULTS: In total, 48,809 patients were included. Very high-volume hospitals demonstrated slightly less pneumonia (6% vs 7%, hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.68-0.88, P < .0001). Very high-volume surgeons experienced slightly higher rates of inpatient morality (3% vs 2%, HR 1.30, 95% CI 1.06-1.60, P = .01), revision surgery (3% vs 3%, HR 1.24, 95% CI 1.02-1.52, P = .03), and implant failure (1% vs <1%, HR 1.80, 95% CI 1.10-2.96, P = .02). Sensitivity analyses did not significantly alter these findings but suggested that inpatient mortality may decline as surgeon volume approaches 30 cases/y before gradually increasing at higher volumes. CONCLUSION: A clinically meaningful volume-outcome relationship was not identified among very high-volume hemiarthroplasty surgeons or hospitals. Although prior evidence indicates that outcomes can be improved by avoiding very low-volume providers, these results suggest that complications would not be further reduced by directing all hemiarthroplasty patients to very high-volume surgeons or facilities. Future research investigating whether inpatient mortality changes with surgeon volume (particularly around 30 cases/y) in a different dataset would be valuable. LEVEL OF EVIDENCE: Prognostic Level III.

Lynch-like syndrome is as frequent as Lynch syndrome in early-onset nonfamilial nonpolyposis colorectal cancer.

Early-onset (<50 years-old) nonpolyposis nonfamilial colorectal cancer (EO NP NF CRC) is a common clinical challenge. Although Lynch syndrome (LS) is associated with EO CRC, the frequency of this syndrome in the EO NF cases remains unknown. Besides, mismatch repair deficient (MMRd) CRCs with negative MMR gene testing have recently been described in up to 60% of cases and termed "Lynch-like syndrome" (LLS). Management and counseling decisions of these patients are complicated because of unconfirmed suspicions of hereditary cancer. To define the prevalence of MMR deficient CRCs, LS and LLS in patients with EO NP NF CRC, we recruited 102 patients with a first diagnosis of NP NF CRC ≤ 50 years old during 2003-2009 who underwent genetic counseling at our institution in Argentina. Tumor immunohistochemical (IHC) MMR for protein expression and microsatellite instability (MSI) status were evaluated, and in those with loss of MLH1 expression by IHC, somatic BRAF V600E mutation and both somatic and germline MLH1 methylation levels were studied. Tumors characterized as MMRd without somatic BRAF mutation nor MLH1 methylation were sent for germline analysis. Twenty one (20.6%) tumors were MMRd. Fourteen of 16 putative LS cases underwent germline testing: 6 pathogenic mutations were identified and 8 cases had no identifiable pathogenic mutations. The prevalence of LS and LLS in this cohort was 5.8% (6/102) and 7.8% (8/102), respectively. As a conclusion we found that 20% of patients with EO NP NF CRC have MMRd tumors, and at least half of these are likely to have LLS.

Preparation and Characterization of P2 BCh Ring Systems (Ch=S, Se) and Their Reactivity with N-Heterocyclic Carbenes.

Four-membered rings with a P2 BCh core (Ch=S, Se) have been synthesized by the reaction of phosphinidene chalcogenide (Ar*P=Ch) and phosphaborene (Mes*P=BNR2 ). The mechanistic pathways towards these rings are explained by detailed computational work that confirmed the preference for the formation of P-P, not P-B, bonded systems, which seems counterintuitive given that both phosphorus atoms contain bulky ligands. The reactivity of the newly synthesized heterocycles, as well as that of the known (RPCh)n rings (n=2, 3), was probed by the addition of N-heterocyclic carbenes, which revealed that all investigated compounds can act as sources of low-coordinate phosphorus species.

Acute and repetitive fronto-cerebellar tDCS stimulation improves mood in non-depressed participants.

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation, which allows for selective inhibition or excitation of neural structures. It has demonstrated some efficacy in the treatment of mood disorders. However, these studies have predominately focused on stimulation of the prefrontal cortex (PFC). The cerebellum has an increasingly recognized role in emotional control, affective state, and some psychopathologies. As such, tDCS research into mood modulation needs to expand beyond conventional PFC-focused paradigms. Using a contralateral stimulation electrode placement [anodal left dorsolateral(dl)PFC, cathodal right cerebellum], and a single-blind, repeated-measures design, we initially assessed changes in the mood of healthy participants in response to acute stimulation (n = 44) and three repeated stimulations delivered second-daily (n = 21). In a second experiment, we separately investigated the influence of reversed polarity upon these same measures, in response to acute stimulation (n = 23) and repeated stimulation (n = 11). We observed a systematic elevation of mood in both active conditions following single and repeated tDCS, the latter of which displayed a progressive elevation of mood from baseline. No mood change was noted in response to either single or repeated stimulation in the sham condition. Frontocerebellar tDCS stimulation advantageously influences mood in healthy participants, with an accumulative and potentiated effect following successive stimulations. The possibility that frontocerebellar stimulation may provide a novel therapeutic adjunctive or pre-emptive intervention in stress-related disorders and mood-related psychopathologies should be considered.

Are Medicare's "Comprehensive Care for Joint Replacement" Bundled Payments Stratifying Risk Adequately?

BACKGROUND: Bundled payments are meant to reduce costs and improve quality of care. Without adequate risk adjustment, bundling may be inequitable to providers and restrict access for certain patients. This study examines patient factors that could improve risk stratification for the Comprehensive Care for Joint Replacement (CJR) bundled-payment program. METHODS: Ninety-five thousand twenty-four patients meeting the CJR criteria were retrospectively reviewed using administrative Medicare data. Multivariable regression was used to identify associations between patient factors and traditional (fee-for-service) Medicare reimbursement over the bundle period. RESULTS: Average reimbursement was $18,786 ± $12,386. Older age, male gender, cases performed for hip fractures, and most comorbidities were associated with higher reimbursement (P < .05), except dementia (lower reimbursement; P < .01). Stratification incorporating these factors displayed greater accuracy than the current CJR risk adjustment methods (R2 = 0.23 vs 0.17). CONCLUSION: More robust risk stratification could provide more equitable reimbursement in the CJR program. LEVEL OF EVIDENCE: Large database analysis; Level III.

Will Medicare Readmission Penalties Motivate Hospitals to Reduce Arthroplasty Readmissions?

BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) recently imposed penalties against hospitals with above-average 30-day readmission rates following total joint arthroplasty (TJA). Hospitals must decide whether investments in readmission prevention are worthwhile. This study examines the financial incentives associated with unplanned readmissions before and after invocation of these penalties. METHODS: Financial data were reviewed for 2028 consecutive primary TJAs performed on Medicare beneficiaries over a 2-year period at an urban academic health system. Readmission penalties were estimated in accordance with CMS policies. RESULTS: Unplanned readmissions generated a $4416 median contribution margin. The initial hospitalizations (when the TJA was performed) were financially unfavorable for patients subsequently readmitted relative to those not readmitted due to increased costs of care (P = .002), but these costs were more than outweighed by the increased reimbursement earned during the readmission (P < .001), ultimately making readmitted patients financially preferable (P < .001). Going forward, penalties will be levied for risk-adjusted readmission rates above the national rate of 4.8%. For the institution under review, the penalty per readmission outweighs the financial gains earned through readmission by $12,184, resulting in a net loss from readmissions if the rate exceeds 6.5%. It will be financially optimal to maintain a readmission rate (after risk adjustment) equal to the national average but exceeding that rate will be $7768 more expensive per readmission than undershooting that target. CONCLUSION: If our results are generalizable, unplanned Medicare readmissions have traditionally been financially beneficial, but CMS penalties outweigh this benefit. Thus, penalties should incentivize institutions to maintain below-average arthroplasty readmissions rates.

Death following ingestion of methylone.

Methylone is a synthetic derivative of cathinone. It is sold principally on the Internet in powder form under the name «bath salts¼. Deaths following consumption are very rare. This report details the first case of a death in France (a 21-year-old man), following ingestion of methylone during an evening with friends. Anoxia was observed at the time of autopsy. Toxicological analyses highlighted a consumption of methylone and cannabis. However, biological analyses showed an absence of ethanol, cocaine, amphetamines, and opiate derivatives. Likewise, no medications were found. High concentrations of methylone were found in the peripheral blood (3.13 mg/L) and in the central blood (6.64 mg/L). Its presence in the gastric contents provides evidence that the substance was taken orally. The dosage of δ9-tetrahydrocannabinol (THC) suggests a recent cannabis consumption (THC 12.9 µg/L, THC-COOH 29.3 µg/L, 11-OH-THC 4.9 µg/L). This case illustrates that the consumption of methylone, which has a reputation of being less «powerful¼ than ecstasy, is not without its dangers.