The authors are pleased to present an expert video roundtable discussion on gluteal augmentation with fat, known widely as the Brazilian Butt Lift, with a focus on the patient safety bills currently being voted on by the Florida legislature (Video). The discussants include a panel of leading experts in aesthetic surgery, and the video roundtable was recorded live at The Aesthetic Meeting 2023 in Miami, FL, USA. The panelists provide an overview of the current challenges, areas of research, and education being undertaken to improve patient safety in gluteal augmentation. As the recording took place, Florida legislators were preparing to vote on bills that would regulate how gluteal fat grafting should be performed and whether plastic surgeons, nurse, or physician's assistants should perform this procedure. The message of these panelists is singular and clear: only board-certified plastic surgeons should perform gluteal augmentation with fat in its entirety. The discussants believe that what happens in Florida represents both an opportunity and a framework for how the rest of the United States will respond to the questions posed about gluteal augmentation.Aesthetic Surgery Journal1–3 and ASJ Open Forum4 and is directly related to patient outcomes and mortality rates. This research has helped save lives. It is imperative that government regulators stand with the board-certified plastic surgeons to improve safety measures that will lead to better patient outcomes and a continued decrease in mortality rates not only in Florida, but worldwide.The overarching goal of this video roundtable is to protect patients and to place their safety at the forefront of the discussion. They review the significance of using ultrasound during gluteal augmentation with fat to allow for clear visual confirmation that the cannula is not in the muscle during fat graft injection. This has been shown and published in the The panelists issue a call to action to all viewers. Visit the following link to let Florida legislators know that you stand with patient safety and that only surgeons should do surgery: mia.one/house.ojad041_Supplementary_DataClick here for additional data file.


Biomaterial-based drug delivery systems have been developed to expedite cartilage regeneration; however, challenges related to drug recovery, validation, and efficient drug delivery remain. For instance, compound K (CK) is a major metabolite of ginsenosides that is known to protect against joint degeneration by inhibiting the production of inflammatory cytokines and the activation of immune cells. However, its effects on cartilage degradation and tissue regeneration remain unclear. Additionally, tissue-adhesive drug delivery depots that stably adhere to cartilage defects are required for CK delivery. In this study, CK-loaded adhesive patches were reported to seal cartilage defects and deliver CK to defect sites, preventing cartilage degradation and accelerating cartilage tissue regeneration. Adhesive patches are stable and suitable for application in surgical procedures under physiological conditions and show excellent adhesiveness to cartilage surfaces. In addition, there were no significant differences in the adhesive polymeric networks before and after CK loading. CK-loaded hydrocaffeic acid-conjugated chitosan patches significantly inhibited the stimulation of cartilage-degrading enzymes and apoptosis in osteoarthritic cartilage by releasing CK in cartilage defects. Additionally, the NFkB signaling pathway of released CK from the adhesive patches in the treatment of osteoarthritis is revealed. Thus, the CK-loaded adhesive patches are expected to significantly contribute to cartilage regeneration.  Cartilage regeneration is a promising strategy for the treatment of osteoarthritis (OA), a degenerative joint disease affecting millions of people worldwide . Howeverhttps://www.gcoopinfo.com/post/the-benefits-of-compound-k-ginseng) [Compound K (CK), a natural compound found in ginseng, possesses anti-inflammatory and antioxidant properties (ginseng) . In addiginseng) , 8. OverFor the successful delivery of chemical drugs, various biocompatible materials have been developed to increase drug delivery efficiency . In addiIn this study, we developed CK-loaded adhesive hydrocaffeic acid-conjugated chitosan (CK/CHI-HCA) patches for patients with OA. Previously, we synthesized CHI-HCA gel patches as capping materials for the directional release of growth factors from heparin-conjugated fibrin gels to prevent migration and dispersion of MSCs from osteochondral defects . We hypoChitosan (medium-molecular weight), dimethyl sulfoxide (DMSO), and methanol (MeOH) were purchased from Sigma-Aldrich . Hydrocaffeic acid (HCA), N-hydroxysuccinimide (NHS), and 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) were purchased from TCI-SU . CK was purchased from ChemFaces . All the other chemicals were of analytical grade.CHI-HCAs were synthesized using standard carbodiimide chemistry. Briefly, chitosan (1 g) was dissolved in pH 2 DDW (100 ml), and the pH was adjusted to 5 using 1 N NaOH. After the complete dissolution of chitosan, HCA (1.13 g), EDC (0.96 g), and NHS (0.71 mg) were added to the chitosan solution dropwise. The pH was maintained between 4.5 and 5.5 during the reactions. After 12 h, the product was purified using a dialysis membrane  against a pH 2 NaCl (10 mM) solution for 2 days and DDW for 4 h. CHI-HCA was obtained by lyophilizing the final product. The HCA conjugation of CHI-HCA was confirmed by 1H NMR  and UV-Vis spectrophotometry .The CHI-HCA patches without CK were prepared using a freeze-drying method. CHI-HCA  was dissolved in DDW and subsequently freeze-dried. The CK/CHI-HCA patches were prepared using a method similar to that described above. Briefly, CHI-HCA (1 wt%) was dissolved in DDW, and CK (5 wt%) was dissolved in MeOH. The HCA solution (0.2 ml) was mixed with the CK solution (20 μl). After homogeneous mixing, the CK/CHI-HCA solution was evaporated to remove MeOH and then freeze-dried.G′) and viscous (G″) moduli were monitored as functions of frequency. The frequency was varied from 0.1 and 10 Hz with 21 points. To compare the CHI-HCA and CK/CHI-HCA hydrogels, a CHI-HCA solution (1 wt%) was used to prepare the CK/CHI-HCA patches. All measurements were performed in triplicate.The rheological analysis of the CK/CHI-HCA patches in pH 7.4 PBS solution was performed using a rotational rheometer . First, CHI-HCA patches without CK prepared with different concentrations of CHI-HCA solution  were placed in the pH 7.4 PBS solution. After 24 h, CHI-HCA hydrogels were obtained. The elastic  films (1×5 cm2) using commercially available cyanoacrylate adhesives. After washing the tissues on the PET films, the two tissues were overlapped, and CK/CHI-HCA patches were applied between them. Tensile strength was monitored after pulling the probe at a loading rate of 1 mm/min.The tissue adhesive properties of the CK/CHI-HCA patches on mouse subcutaneous regions and porcine cartilage  were evaluated by measuring the tensile strength using a universal testing machine  with a 50 N load cell. Before measuring tensile strength, mouse subcutaneous regions were cut into 1×1 cmCell viability was measured using Muse Annexin V and Dead Cell Kits (Luminex). Cells were incubated with annexin V and propidium iodide solutions, and fluorescence was analyzed using a Muse Cell Analyzer (Merck Millipore).2.The immature murine articular chondrocytes (iMACs) were isolated from postnatal Day 5 pups according to a previously published method . iMACs were cultured with Dulbecco’s modified Eagle’s medium (Gibco) with 10% fetal bovine serum (Gibco) and 100 units/ml of penicillin and streptomycin at 37°C supplied with 5% COIn Situ Cell Death Detection Kim (Roche) was used with deparaffinized cartilage sections according to the manufacturer’s instructions. Images were acquired by fluorescence microscopy after nuclear staining with 4′,6-diamidino-2-phenylindole.Cell proliferation was measured using the Quick Cell Proliferation Colorimetric Assay Kit  with a Muse Cell Analyzer (Merck Millipore) following the manufacturer’s instructions.Destabilization of the medial meniscus (DMM) surgery was performed on the left knee joint of 8-week-old mice without cutting the ligament as a control. At 8 weeks after DMM surgery, the knee joint tissues were processed for histological analysis. All animal experiments were performed in accordance with the guidelines of the Institutional Animal Care and Use Committee (IACUC) of Wonkwang University. All animal experiments were approved by the Animal Ethics Committee of Wonkwang University (WKU22-122).Cartilage samples were fixed with 10% neutral-buffered formalin for 24 h and decalcified using 0.5 M ethylenediaminetetraacetic acid solution for a week. After paraffin embedding, blocks were cut at 5 μm thickness and stained with safranin O. For immunohistochemical analysis, deparaffinized sections were incubated with primary antibodies overnight at 4°C in a humidified chamber. The sections were subsequently developed using ImmPACT DAB . The following antibodies were used for immunohistochemical analysis: MMP13 , MMP 3 , ADAMTS4 , pIΚB , IκB , and horseradish peroxidase-conjugated goat anti-rabbit IgG .Reverse-transcribed using 5X All‐in‐One RT Master Mix . Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed using AMPIGENE qPCR Green Mix . RN18S was used as an endogenous control. The qRT-PCR primer sequences used in this study are listed in 1H NMR spectroscopy, and UV-Vis spectra were obtained. The catechol protons of CHI-HCA were found in the range of 6.5–7.0 ppm in the 1H NMR spectra (Hydrocaffeic acid-conjugated chitosan (CHI-HCA) was synthesized using an EDC coupling agent. As shown in  spectra . In addi spectra . The deg spectra . The CK/ spectra . As show spectra , bottom. spectra  and CK/C spectra . HoweverG′) of CHI-HCA patches in the PBS solutions after 24 h were increased as a function of CHI-HCA concentration  and viscous (G′′) modulus values of CHI-HCA were monitored as a function of frequency  were cultured with different concentrations  of CHI-HCA extracts for 24 h . There wiMACs were cultured to explore the effects of CK on chondrocyte differentiation . ChondroAcan and Comp were significantly increased in the cartilage with CK-loaded CHI-HCA patches in DMM mice. Severe cartilage degradation, as assessed by safranin O staining, observed in the cartilage of DMM mice was dramatically reduced in cartilages with CK-loaded CHI-HCA patches (MMP-3 and ADAMTS-4 were significantly reduced in the cartilage with CK-loaded CHI-HCA patches in DMM mice (To investigate the effects of CK on the pathogenesis of OA, DMM was performed to induce OA pathological conditions . In OA c patches . Immunoh patches . In addiDMM mice . These dTo identify the underlying signaling mechanism, we searched PubMed and identified common signaling pathways regulated by OA pathogenesis and CK treatment. Among them, we found that the number of pIkBα-positive cells was significantly decreased, whereas the number of IkBα-positive cells was significantly increased in the cartilages with CK-loaded CHI-HCA patches of DMM mice compared to DMM cartilage , suggestIn summary, ginsenoside CK-loaded adhesive patches were developed for cartilage tissue engineering. The CHI-HCA patches showed excellent adhesion to porcine cartilage and could deliver CK to cartilage tissues by sealing cartilage defects. The CK drugs from the CHI-HCA patches were effective in the prevention of cartilage degradation by inhibiting degradative enzymes and apoptotic cell deaths via inhibiting NFkB signaling. Thus, we expect that CK-loaded adhesive patches have enormous potential as drug-loaded sealing materials for cartilage regenerations and the prevention of further cartilage degradation, particularly for the surgical treatment of cartilage repair.rbad077_Supplementary_DataClick here for additional data file.


Diverse race and ethnicity representation remains lacking in science and technology (S&T) careers in the United States (US). Due to systematic barriers across S&T training stages, there may be sequential loss of diverse representation leading to low representation, often conceptualized as a leaky pipeline. We aimed to quantify the contemporary leaky pipeline of S&T training in the US.We analyzed US S&T degree data, stratified by sex and then by race or ethnicity, obtained from survey data the National Science Foundation and the National Center for Science and Engineering Statistics. We assessed changes in race and ethnicity representation in 2019 at two major S&T transition points: bachelor to doctorate degrees (2003–2019) and doctorate degrees to postdoctoral positions (2010–2019). We quantified representation changes at each point as the ratio of representation in the later stage to earlier stage (representation ratio [RR]). We assessed secular trends in the representation ratio through univariate linear regression.For 2019, the survey data included for bachelor degrees, 12,714,921 men and 10.612,879 women; for doctorate degrees 14,259 men and 12,860 women; and for postdoctoral data, 11,361 men and 8.672 women. In 2019, we observed that Black, Asian, and Hispanic women had comparable loss of representation among women in the bachelor to doctorate transition , while among men, Black and Asian men had the greatest loss of representation ]. We observed that Black men  and Black women  experienced the greatest loss of representation among men and women, respectively, in the doctorate to postdoctoral transition. Black women had a statistically significant decrease in their representation ratio in the doctorate to postdoctoral transition from 2010 to 2019 (p-trend = 0.02).We quantified diverse race and ethnicity representation in contemporary US S&T training and found that Black men and women experienced the most consistent loss in representation across the S&T training pipeline. Findings should spur efforts to mitigate the structural racism and systemic barriers underpinning such disparities. Representation of diverse race and ethnicity groups in the science and technology (S&T) workforce remains lacking in the United States (US) despite research and governmental recognition of the problem –5. BlackPrior work using data from 2000 to 2013 assessed the journey of Black, Hispanic, and AI/AN populations across the training pathway from high school to research faculty positions in the biomedical sciences in the US, finding losses of representation mainly during undergraduate studies, with otherwise minimal losses of attrition in the receipt of a doctorate degree or receipt of a postdoctoral position [We obtained cross-sectional 2003–2019 S&T  degree data from the National Science Foundation and the National Center for Science and Engineering Statistics which was comprised of findings from the National Survey of College Graduates, the Survey of Doctorate Recipients, and the Survey of Graduate Students and Postdoctorates in Science and Engineering (2010–2019). Race and ethnicity groups were included based on available data: Non-Hispanic White (NHW), Non-Hispanic Black (Black), Non-Hispanic Asian (Asian), Hispanic or Latino (Hispanic), and Non-Hispanic AI/AN. In NCSES survey data, those classified as Hispanic or Latino may be of any race, while those categorized as a race exclude those of Hispanic ethnicity. Temporary visa holders were excluded from the analysis because their race or ethnicity data are not reported. We calculated race or ethnicity group representation (%) separately for men and women and evaluated two transition points: bachelor to doctorate degree receipt, and doctorate degree receipt to postdoctoral positions. We quantified differences in representation at each transition as the ratio of representation in the subsequent stage to that of the previous stage in the same year. A representation ratio less than 1 indicated loss of representation across that transition point. We calculated 95% confidence intervals (CIs) for the representation ratios in the standard manner as for risk ratios. AI/AN data were excluded due to very low sample sizes  with consequent limited interpretability and reliability. We assessed trends over time in representation ratios using univariate linear regression. A p-trend threshold of 0.05 denoted statistical significance. R, version 4.0.0, was used for statistical analyses.In 2019, the survey data included the following total populations: for bachelor degrees, 12,714,921 men and 10.612,879 women; for doctorate degrees 14,259 men and 12,860 women; and for postdoctoral data, 11,361 men and 8.672 women. In 2019, NHW men  and women  had the highest representation, followed by Asian, Hispanic, and Black groups .In 2019, Black, Asian, and Hispanic women had comparable losses in representation , while NHW women had the lowest change  groups defined as Black, Hispanic, and AI/AN groups was minimal in the receipt of doctoral degrees and the receipt of a postdoctoral position within the biomedical sciences [This analysis does not capture other transitions including high school to undergraduate or postdoctoral to faculty. The pipeline concept does not incorporate all S&T careers; for instance, postdoctoral training may not be relevant to non-tenure track academic or industry positions, or entrepreneurial careers. Heterogeneity by disaggregated groups or disaggregated fields of study was not captured in these data. Higher Asian representation may reflect decreasing representation in other groups and should be interpreted with caution. Those on temporary visas were not captured in this analysis. These data aim to explore longitudinal trends using serial cross-sectional survey data and should be interpreted within these limitations.In conclusion, Black men and women experienced the greatest representation losses across the aggregated US S&T training pipeline from bachelor degrees to postdoctoral positions with no significant evidence of improvement over a contemporary time period.


Carbonic anhydrases (CAs) are important regulators of pH homeostasis and participate in many physiological and pathological processes. CA activators (CAAs) are becoming increasingly important in the biomedical field since enhancing CA activity may have beneficial effects at neurological level. Here, we investigate selected antihistamines, phenothiazine-based antipsychotics, and tricyclic antidepressants (TCAs) as potential activators of human CAs I, II, IV, and VII. Our findings indicate that these compounds are more effective at activating hCA II and VII compared to hCA I and IV. Overall, hCA VII was the most efficiently activated isoform, particularly by phenothiazines and TCAs. This is especially relevant since hCA VII is the most abundant isoform in the central nervous system (CNS) and is implicated in neuronal signalling and bicarbonate balance regulation. This study offers additional insights into the pharmacological profiles of clinically employed drugs and sets the ground for the development of novel optimised CAAs. In this context, the reversible hydration of carbon dioxide  and the multitude of isoforms present in each of them, which represents one of the most dramatic instances of convergent evolution in biology.,via a glycosylphosphatiydyl-inositol and faces the extracellular space;,,,,,,,The catalytically active human CAs (hCAs) are distinct based on their subcellular localisation: hCA I-III, VII, and XIII are cytosolic;1) to hCA II ,o hCA II  and indin medium . In the 1 has been co-crystallised with hCA II, many other CAAs have been identified, and different co-crystal structures of hCA I/II in complex with CAAs have been reported, including those with L- and D-His,,Ever since From a therapeutic point of view, the primary applications of CAAs are in the fields of pharmacological augmentation of synaptic efficiency, spatial learning, and memory.,,In line with the importance of hCA activation in the CNS, many psychoactive drugs and therapeutically used histamine receptor modulators, including antihistamines, all of which bear potential PSMs , have been recently indicated to also act as CAAs.1 receptor (H1R) inverse agonists diphenhydramine (2),3),1R inverse agonists fenethazine (4) and promethazine (5),6, the phenothiazine-based neuroleptic drugs promazine (7), 9–12,8,,13–18 . Compounds 4, 6, and 8 were commercially available, highest purity derivatives from Ambinter SARL, Hong Kong Chemhere Co. Ltd, and Enamine Ltd, respectively.Compounds 2 hydration was monitored via a stopped-flow method2 hydration reaction for 10 to 100 s. For every compound, at least six traces of the initial 5–10% of the reaction were employed for establishing the initial velocity. The uncatalysed rates were measured with the same approach and subtracted from the total rates. Stock solutions of each compound (0.1 mM) were prepared in distilled-deionised water and dilutions up to 0.1 nM were prepared using the assay buffer. The activation constant (KA), defined in a similar way as the inhibition constant (KI), was calculated using the classical Michaelis–Menten  ≪ KM), and because [A]f can be defined in the form of the total concentration of the enzyme ([E]t) and activator ([A]t), the obtained competitive steady-state equation for calculating the activation constant is given by 0v represents the initial velocity of the enzyme-catalysed reaction in the absence of activator. All CA isoforms used in the experiments were purified recombinant proteins obtained as already reported.Since the assays were carried out at substrate concentrations significantly lower than the 1) was among the first uncovered CAAs, and histamine receptor modulators have been recently investigated for their potential as CAAs.2 and phenothiazine derivatives 4 and 5. We also evaluated the anticholinergic compound 3, possessing a scaffold similar to 2, but with an additional carbonyl spacer between the oxyethylamine and benzhydryl moieties, and compound 6, the bis desmethyl derivative of 5. Given the phenothiazine-based structure of the first-generation H1 antihistamines 4 and 5, we went on to evaluate the CA activation potential of the phenothiazine-based neuroleptics 7, and 9–12, as well as the desmethyl metabolite of 7, compound 8.,13–18, structurally characterised by an expansion of the central ring of phenothiazines from a 6-membered to a 7-membered cycle  and none of them outperformed 1 in increasing hCA I activity, with the most potent ones being 3 (KA = 10.2 µM) and 13 (KA = 9.3 µM). The demethylation of 13 decreased hCA I activation potency, as demonstrated by the KA value measured for the mono desmethyl analogue 14, which is >2.5-fold higher (KA = 24.8 µM).Only four compounds exhibited cytosolic hCA I activation  being the most potent hCA II activator (KA = 1.4 µM), immediately followed by triflupromazine (10) and imipramine (13), with KA values of 1.9 and 2.0 µM, respectively. Notably, demethylation had divergent effects on hCA II activation for 13 and the rest of the assayed compounds. Indeed, the double demethylation of 5 and the mono demethylation of 7, leading to 6 and 8, respectively, increased the hCA II activation profile by 1.5- to 2.6-fold. Similarly, removal of a methyl group from 15 augmented hCA II activation , while the opposite effect was observed in the case of 13, since its mono desmethyl derivative 14 was ∼2-fold less potent.The cytosolic hCA II was activated by all tested compounds, apart from 1 was 14, with a KA value of 10.0 µM. Notably, in this case, methylation of the exocyclic nitrogen decreased CA activation potency, with 13 showing a ∼2.8-fold higher KA. The same pattern could be observed for phenothiazines 7 and 8, with the mono desmethyl derivative 8 having a KA value of 27.6 µM, while 7 was essentially not active (KA > 50 µM).The membrane-anchored hCA IV displayed an activation profile analogous to that observed for hCA I, with only few molecules capable of enhancing its activity. The only compound exhibiting a hCA IV activation more efficient than 1, with a wide range of derivatives being active in the low micromolar range. Specifically, half of the assayed compounds exhibited a KA value lower than 5 µM. These include: (i) the benzhydryl derivatives 2 and 3; (ii) the phenothiazine-based compounds 7, 10, 11, and 12; (iii) the TCAs 13, 14, and 17. Among the tested molecules, the most promising hCA VII activator was desipramine 14 (KA = 1.6 µM), the mono desmethyl analogue of 13, which could still activate hCA VII, albeit almost 2-fold less efficiently. The same structure-activity relationship (SAR) was observed for TCAs 15 and 16, with the mono desmethyl derivative being >2-fold more potent than its parent compound 15. Conversely, the phenothiazines bearing a 1,3-diaminopropane chain (7 and 8) followed the opposite trend, with 7 being ∼3.5-fold more potent than the mono desmethyl analogue 8. In the case of the phenothiazine-based 1,2-diaminopropane compounds 5 and 6, removal of both N-methyl groups led to a 3-fold decrease in CA VII activation potency. Interestingly, compound 2, which was inactive towards all other isoforms, was a good hCA VII activator (KA = 4.7 µM). Similarly, TCAs 17 and 18, which were only weakly potent towards hCA II, could both activate hCA VII with KA values of 4.9 and 9.2 µM, respectively.The cytosolic hCA VII was efficiently activated by the compounds investigated in the study, and all of them possessed an improved activation profile compared to 2 and 3 preferentially activated hCA VII, with 2 being hCA VII-selective, while 3 was one of the few pan-hCA activators among the assayed compounds.The benzhydryl compounds 4, 5, and the bis desmethyl derivative 6) and neuroleptics (7–12) displayed selective hCA II/VII activation properties. Specifically, compound 7 and its derivatives 9 and 10, possessing an electron-withdrawing moiety at C2 of the phenothiazine core, displayed KA values in the low micromolar range for both hCA II and VII. In this series, compounds 4 and 5 and, partly, 6 were slightly less potent towards both isoforms, and this may be ascribed to the shorter 2-carbon spacer between the endocyclic and exocyclic nitrogen atoms. Moreover, 11 and 12 suffered from a significant drop in hCA II activation compared to analogues 7–10. In this case, the only difference between the tested compounds is the presence of a bulkier substituent at C2 of the phenothiazine core in 11 and 12.Both phenothiazine-based antihistamines  was detrimental for compound activity. Moreover, in compounds 17 and 18, the ethylene bridge between the two phenyl rings was replaced by a double bond or by inserting an oxygen atom, and this further modification especially affected their hCA II activation potency. As a result, the 10,11-dihydro-5H-dibenzoazepine core represented the preferred chemotype for hCA II/VII activation, despite its lack of selectivity. On the other hand, the 5H-dibenzo[7]annulene core offered a fair compromise between hCA activation and selectivity, as exemplified by compound 17, the most hCA VII-selective activator among the tested TCAs.TCAs were endowed with a similar activation pattern to phenothiazines, with all compounds preferentially activating hCA II and VII. In this case, while compounds By looking at the different chemical classes of the analysed compounds, we could also draw some interesting SAR:Finally, as illustrated in the "Literature Data" section of 2 and 3 displayed preferential activation towards hCA VII, while both phenothiazine-based compounds and TCAs could activate both hCA II and VII, with an overall slight preference of phenothiazines towards hCA II. Among the tested compounds, the phenothiazine derivative promazine (7) displayed the best profile in terms of potency and hCA II/VII selectivity over the other hCA isoforms. TCAs 13 and 14, on the other hand, were essentially non-selective, and modifications to their 5H-dibenzoazepine core, although improving the selectivity towards hCA VII, lowered compound potency, as evidenced by the activity profiles of 17 and 18.In this study, we examined the hCA activating properties of a variety of clinically-approved drugs (or derivatives thereof, 9 and is involved in the maintenance of the bicarbonate gradient in neurons as well as neuronal signalling.Remarkably, hCA VII was overall the most efficiently activated isoform by the compounds evaluated in our analysis. This is of significant relevance since hCA VII is the most abundant CA in the human CNS,,,Furthermore, the evidence collected through this study offers additional insights into the pharmacological profile and therapeutic effects of clinically employed drugs such as antihistamines, phenothiazine-based antipsychotics, and TCAs. Indeed, both their therapeutic activity and adverse effects are connected to polypharmacology-based mechanisms, and the enhancement of hCA activity should now be considered. Ultimately, the present research may provide novel perspectives into the complex network linking hCA function and CNS homeostasis. Indeed, while CAAs have only recently been considered for their pharmacological applications in memory and cognition therapy,


Placental extract has been mostly used in skin care for cosmetic purposes. However, the use of various placental extracts has been limited due to the lack of established and effective application methods.In this study, we investigated the antiwrinkle effect of a cream formulation—LNC wrinkle eye cream (LNC-EC)—containing horse placental extract as the main ingredient.A total of 24 healthy women, aged 37-54 years, with wrinkle grades 1-3, were treated with LNC-EC for 2 weeks. The cream was applied on one-half of the participants’ faces, and the results were compared with the untreated half of the face.Visual inspection, using the wrinkle grade standard, showed that the area treated with LNC-EC had a significantly lower wrinkle grade than the untreated area when comparing before and after the application of LNC-EC. In addition, replica analysis showed a significant reduction in both the maximum wrinkle width and the number of wrinkles in the LNC-EC–treated area in comparison to the untreated area before and after the application. These results suggest that LNC-EC has an antiwrinkle effect on the corners of the eyes based on parameters like the maximum wrinkle width and the number of wrinkles.LNC-EC, with horse placental extract as its main ingredient, was shown to be effective in improving wrinkles at the eye corners, presumably due to a reduction in the maximum wrinkle width and the number of wrinkles. Interpretation of the results is limited because this study was conducted only in the intervention group. A randomized controlled trial with a placebo control group is necessary to verify the antiwrinkle effects of horse placental extract. Skin aging is influenced by both internal  and extDermatologically, placental extracts have been reported to enhance epidermal protection by promoting keratinocyte proliferation, increasing antibacterial peptide expression , reducing cell damage from fine particulate matter, supporting the growth of epidermal indigenous bacteria, and inhibiting cellular aging during 5-bromo-2’-deoxyuridine induction ,9. AlthoThe LNC wrinkle eye cream  was used.This randomized, single-blind clinical trial was conducted from January 20 to February 3, 2022, in Kirei Testing Labo Co, Ltd. We established a single group to compare the untreated and treated sites in the same participant. Randomization was performed to reduce bias.This study was reviewed and approved by the Kirei Testing Laboratory Ethics Committee on January 18, 2022 (ID 22000134) and registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000051646). The participants signed an informed consent, which included the study purpose, methods, confidentiality, and the right to withdraw. Confidentiality was ensured. Study procedures were conducted according to the World Medical Association’s Helsinki Declaration and its amendments.The inclusion criteria were as follows: healthy Japanese women aged ≥20 and <59 years at the time of consent, women with wrinkle grades 1 to 3 at both eye corners, and women with skin classified as Fitzpatrick type III or IV. Exclusion criteria included the following:Women with markedly different wrinkle grade scores  between the left and right eye cornersWomen whose skin at the evaluation site had inflammation, trauma, contusion, pimples, warts, blemishes, or traces of diseases like atopic dermatitis or urticaria that may affect study resultsWomen continuously using skin care products, cosmetics, quasi-drugs, or health foods claiming or emphasizing similar efficacy as the test product (reduction of fine lines and wrinkles caused by dryness) at the evaluated areaWomen who had undergone or planned to undergo cosmetic procedures on the evaluation site or elsewhere during the study periodWomen who changed their skin care products or started using new basic cosmetic or sunscreen products on the evaluation site within the past 4 weeksWomen exposed to excessive ultraviolet radiation  within the past 4 weeks or planning such activities during the studyWomen participating in another study at enrollment or during the planned study durationWomen receiving hormone replacement or any other treatments for various medical conditions at enrollment or during the studyWomen currently undergoing dermatological treatmentWomen with a history of serious diseases involving glucose and lipid metabolism; liver and renal function; cardiac, cardiovascular, respiratory, endocrine, immune, and neurological systems; or psychiatric disordersWomen working night or a combination of day and night shiftsWomen with a history of alcohol and drug dependence12, or melatonin for sleepingWomen who take alcohol, vitamin BWomen at risk of developing allergies to cosmetics and food or who have developed skin rashes or other skin problems due to cosmetics within the past yearPregnant or lactating women at the time of consent or those planning to become pregnant during the studyWomen using mosaics, eye tapes, or other double-eyelid-shaping products that cannot be removed for testingWomen who had eyelash extensions and could not tolerate the solvent used during the replica collectionParticipants deemed ineligible for any reason by the supervising physician or investigatorIf any information rendering them ineligible was identified during the study, they were excluded from the analysis. A total of 24 participants were selected for the study through visual assessment based on the wrinkle grade standard (8 grades: 0-7). Informed consent was obtained from all participants. Furthermore, a consultation service was established at a medical institution to address any health-related enquiries.Test products were randomly assigned to participants using the half-face method on symmetrical areas of the face, with no apparent bias in the left-right distribution . ParticiPhotographic and visual assessments were conducted in accordance with the guidelines for evaluating antiwrinkle products, as authorized by the Japanese Cosmetic Science Society. Trained experts, proficient in wrinkle evaluation, assigned participants an 8-point wrinkle grade score using the wrinkle grade evaluation criteria and photographs provided by the Japanese Society of Cosmetic Science and Technology .Skin replicas of the target site (10 × 10 mm or larger) were made and analyzed using a replica analysis system  to calculate the wrinkle area and volume ratios, maximum wrinkle depth and width, average wrinkle depth, and the number of wrinkles .t test (P=.05) for wrinkle and replica analysis, respectively, to determine statistically significant differences in improvement between the untreated and treated sides.The untreated and treated sides were compared by calculating the change (Δ) at 2 weeks . Skin replica analysis was performed using a statistical software program built into the replica analysis system . For each clinical parameter, the groups were compared using the Wilcoxon signed rank test and a paired 2-tailed The wrinkle grade on the treated side was 2.25 at baseline but decreased to 2.0 after 2 weeks of use, resulting in less noticeable wrinkles. On the untreated side, the grade remained at 2.0 from baseline to the end of the 2-week period A. A signNo significant differences were observed in pre- and posttest results for wrinkle area ratio, wrinkle volume percentage, maximum wrinkle depth, and wrinkle mean depth. Meanwhile, a significant difference was detected in pre- and posttest results for maximum wrinkle width and the number of wrinkles .In this study, LNC-EC was applied to healthy participants for 2 weeks to verify its cosmetic effects. Both wrinkle grade evaluation and replica analysis demonstrated its antiwrinkle effects at the eye corners. The replica analysis revealed a reduction in the maximum width and the number of wrinkles. These results suggest that horse placental extract has cosmetic benefits.Staphylococcus epidermidis and antimicrobial peptide expression in human epidermal keratinocytes [Wrinkles can result from external factors like dryness due to decreased temperature and humidity as well as internal factors related to reduced moisture retention due to aging. This study was conducted during winter when temperature and humidity levels are at their lowest. Consequently, external factors could potentially compromise the barrier function of each skin layer. The stratum corneum’s barrier function weakens during winter due to smaller corneocytes compared to summer . Epiderminocytes . Furtherinocytes . Horse pinocytes , suggestUltraviolet B stimulates epidermal keratinocytes, resulting in the release of inflammatory cytokines , which stimulate dermal fibroblasts and keratinocytes to increase matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9—enzymes that degrade collagen and elastic fibers, causing wrinkles . Horse pLNC-EC appears effective in improving the appearance of eye-corner wrinkles, presumably by reducing their maximum width and number. No adverse events associated with LNC-EC application were observed during the study, indicating its safety for use.


In this paper, we propose a sequential variational autoencoder for video disentanglement, which is a representation learning method that can be used to separately extract static and dynamic features from videos. Building sequential variational autoencoders with a two-stream architecture induces inductive bias for video disentanglement. However, our preliminary experiment demonstrated that the two-stream architecture is insufficient for video disentanglement because static features frequently contain dynamic features. Additionally, we found that dynamic features are not discriminative in the latent space. To address these problems, we introduced an adversarial classifier using supervised learning into the two-stream architecture. The strong inductive bias through supervision separates dynamic features from static features and yields discriminative representations of the dynamic features. Through a comparison with other sequential variational autoencoders, we qualitatively and quantitatively demonstrate the effectiveness of the proposed method on the Sprites and MUG datasets. Representation learning, which involves the acquisition of low-dimensional latent variables from high-dimensional data such as videos and images, is an essential task in computer vision. Disentangling latent variables and associating one generative factor with one latent variable are objectives of representation learning. Such a disentangled representation can be helpful for downstream tasks, such as causal and controllable inferences, prediction, and generation .Typical deep generative models for disentanglement include variational autoencoders (VAEs)  and geneSeveral studies have investigated image disentanglement using VAEs ,11,12. LNevertheless, Luo et al.  pointed We identify the following two underlying problems caused by the basic two-stream VAE architecture for video disentanglement: (i) the static feature of a given video may include dynamic features; (ii) dynamic features are not discriminative in the latent space. To the best of our knowledge, no previous study has explored these problems.We propose a sequential VAE with an adversarial classifier to solve these two problems simultaneously. The supervision by an adversarial classifier provides a strong inductive bias for these problems. Moreover, we demonstrate that the adversarial classifier excludes dynamic features from the static feature, yielding discriminative dynamic features.Adversarial classifiers are used for various applications, such as cross-domain image generation ,23, faceThe remainder of this paper is organized as follows: VAEs are typically used to disentangle features. Earlier studies improved image disentanglement by adjusting the Kullback–Leibler (KL) divergence term for variational inference. Higgins et al.  introducInductive biases divide videos into static and dynamic features. Typical VAEs use deep recurrent models to disentangle the sequential data. Chung et al.  incorporZhu et al.  proposedIn this study, we incorporated an adversarial classifier  into theWe propose a two-stream sequential VAE with an adversarial classifier for video disentanglement, as shown in t of an input video of length T. The loss function for variational inference is expressed as follows:q and p. The weights of the decoder D and dynamic encoder The sequential VAE encodes sequential data, such as video or audio, into latent variables  follows:Lvae and and6) an 8:             9:             10:           11:           12:           13:    Update parameters end while 14: return 15: In summary, we minimize the total loss function of the VAE loss in Equation  and gradWe evaluated the effectiveness of the auxiliary adversarial classifiers on the Sprites  and MUG  The MUG  dataset  The MUG ,17. The We compared the proposed method with DSVAE  using a In this experiment, we investigated whether the adversarial classifier can solve the overlapping problem in dynamic features, as shown in In this experiment, we evaluated the disentanglement performance of the proposed method using randomly generated videos. The procedure for random video generation was as follows: First, we input a video from the Sprites or MUG dataset into the sequential VAE and extracted static and dynamic features. Next, we fixed one of the two features and replaced the other feature with a randomly generated feature from the prior distribution. The sequential VAE decoder generated the random video by concatenating the two features. If the sequential VAE disentangled the random video into static and dynamic features, we obtained the video conditioned on fixed and randomly generated features.We next generated video examples by randomly sampling the static feature from the prior distribution We summarize the experimental results as follows: Because DSVAE did not disentangle the videos into static and dynamic features, the static features partly included dynamic features. In contrast, the proposed method outperformed DSVAE in terms of disentanglement performance and video quality.We compared the proposed method with four sequential VAEs: DSVAE , S3VAE , R-WAE , and C-DA classifier determines whether each sequential VAE generates the desired videos. Similar to , we prepk. If input videos are uniformly sampled, the class probability is As explained in In contrast, We evaluated disentanglement performance using three entropy-based metrics: inception score (opy H(y) . For evaIn this study, we introduced an auxiliary adversarial classifier into the sequential VAE to strengthen the induction bias for video disentanglement. With the basic two-stream VAE architecture, static features tend to include dynamic features, which are not discriminative in the latent space. Our experiments demonstrated that the proposed method with the adversarial classifier could simultaneously solve these problems. The proposed method also outperformed the previous studies in three evaluation metrics.The proposed method provides a strong inductive bias for video disentanglement using supervised learning, that is, it requires class labels to learn the adversarial classifier.Therefore, the proposed method cannot be used with data that lack random behaviors or class labels for dynamic features. The adversarial classifier needs only class labels for dynamic features, not static ones. In this sense, our approach can be categorized as weakly supervised learning. To mitigate weakly supervised learning, two possible directions may be taken for future work. One is adopting a self-supervised learning technique such as pseudo-labeling. The other is using semi-supervised learning by utilizing a combination of labeled and unlabeled data for training. These techniques reduce the labeling burden while retaining the strong inductive bias through supervision for application in various downstream tasks.


To explore a method of constructing an orthotopic ileal neobladder (ONB) in the Y-pouch configuration. We describe the steps followed to create the Y-pouch ileal orthotopic neobladder (ONB) and compared the perioperative, functional, and urodynamics outcomes with the Studer neobladder technique.A retrospective cohort study of 90 bladder cancer patients, who received open radical cystectomy with the ONB performed at a hospital from June 2009 to May 2020. These patients were divided into two groups—the Y-pouch and the Studer neobladder groups. Perioperative, functional outcome, complication, renal function data outcomes, and pressure–volume study were used to evaluate the treatment outcomes after a radical cystectomy.p = 0.826). At 30 days postoperatively, the Clavien-Dindo classification of surgical complications revealed grade-2 urinary infections in two patients (5.6%) and six patients (11.1%) for the Y-pouch and Studer techniques, respectively. Intermediate complications (30–90 days) were reported in 4 (11.1%) and 18 patients (44.4%) in the Y-pouch and the Studer techniques, respectively (p = 0.062). In the urodynamics study (UDS), the Y-pouch group had a mean postvoid residual volume of 20 mL and Studer of 40 ml (p = 0.06). A mean capacity of 462 (380–600) mL compares to the Studer neobladder group with 495 (400–628) mL. The average mean compliance of the Studer group was 35.5 (28–52) ml/cm H2O and 33 (30–43) ml/cm H2O for Y pouch, and most patients had > 30 ml/cm H2O compliance (80/90 patients).Ninety patients (54 Studer and 36 Y-pouch neobladder) were enrolled. The median patient age was 62.6 (± 11) years. The mean operative time for the Studer technique was 290 (242.5–350) min, and the Y-pouch technique was 300 (271.2–335) min) (The Y-pouch neobladder technique in an RC with an orthotopic neobladder provides perioperative and functional outcomes compared to those of the Studer orthotopic neobladder resulting in similar intermediate-term. Therefore, the Y-pouch ileal neobladder is both feasible and safe to be used as a standard neobladder technique for urinary diversion in patients with bladder cancer undergoing radical cystectomy and needs confirmation with long-term results. A radical cystectomy (RC) is an effective method for the treatment of invasive bladder cancer, with an ileal orthotopic neobladder (ONB) reconstruction being an ileal method of urinary diversion , 2. An oInitially, as described by Camey, a small tubular bowel segment has been used as a bladder substitute for the creation of an ONB and a tubular bowel segment anastomose is performed to the urethra directly without detubularization . SubsequThe aim of the study was to explore a new method of constructing an ONB in the Y-pouch configuration. Focusing on patients treated with open RC, we describe the steps followed to create the Y-pouch IONB. We also compared the perioperative and functional outcomes of this approach with those of the Studer neobladder technique.This study was a retrospective analysis of the clinical data of 90 patients with bladder cancer, who underwent an RC with ONB at a university hospital, from June 2009 to May 2020. Among them, 36 were treated using the novel Y-pouch technique and 54 were treated using the neobladder technique. Both the cystectomy and reconstruction with a Y-pouch and Studer techniques were performed using open surgery. Their clinical preoperative, perioperative, and also postoperative data were reviewed. The decision-making process for selecting the method of establishing the neobladder involved a comprehensive evaluation based on various clinical indicators and principles of surgical protocol development. The selection bias method of establishing the orthotopic neobladder is determined according to time bias, with more including the Studer technique in the early period and the Y-pouch technique in the late period. All cases were performed under highly experienced urologists. Also, ERAS management and cystostomy were not applied routinely in all cases.A 40-cm ileal segment was harvested, the starting point of which was selected at 15 cm from the ileocecal junction . The ureters are then individually connected to the afferent tubular ileal segment in an end-to-side manner. This part of the procedure is identical to the traditional Studer technique, until the posterior surface of the bladder substitute is formed, as shown in Fig. We removed the ureteric stent on the postoperative 5th day and administered a single-shot IV third-generation cephalosporin before stent removal. The patient was discharged after the Jackson-Pratt drain was removed or after the removal of the Foley catheter on postoperative days 28 with proof of no leakage from the cystogram. At 1 month, the first postoperative evaluation was performed and self-bladder irrigation was started. After the treatment, we carried out postoperative reviews of the patients at 1 month, and then at 3, 6, and 12 months, and at least yearly thereafter. The review included a clinical examination, an assessment of the renal function , and routine laboratory values as well as computerized tomography scans of the chest and abdomino-pelvis scan or KUB ultrasound.The observation indicators of this study were as follows. First, the baseline parameters of the patients. Second, the perioperative and postoperative outcome observation indicators included early and late complications, daytime continence, nighttime continence, continence status, capacity, residual urine, and the Clavien-Dindo classification . ContineThe capacity of the neobladder was measured by ultrasound or cystography under fluoroscopy. The outcomes were compared between the Y-pouch and the standard Studer neobladder groups .2O). Provocative testing  was used to assess stress urinary incontinence and abdominal leak-point pressure (ALPP) at maximum cystometric capacity.All urodynamics study (UDS) measurements were analyzed at 12 months following the surgery. The patients are placed in a sitting position. Noninvasive uroflowmetry and postvoid residual volume (PVR) were assessed at the beginning of the procedure. The change in volume per increase in pressure during the filling phase was used to calculate compliance (ml/cm Ht tests or Wilcoxon tests. The count data were represented by examples (n) and frequencies (%), and Pearson’s chi-square test or Fisher’s exact test was used for intergroup comparisons. P < 0.05 was considered to indicate statistical significance.The R program version 4.0.1 was used for the statistical analysis of our data. All the quantitative data were represented by a mean ± SD or an interquartile range (IQR), and comparisons between 2 different time points (change of eGFR and creatinine for each subject over a 12-month period) were performed using paired p = 0.826). The mean amount of blood loss  was not statistically significant (p = 0.149).A total of 90 neobladder cases were included in our study. They were stratified into 2 groups according to the surgical technique that was used for the orthotopic urinary diversion—the Studer and Y-pouch neobladder techniques as shown in Table p = 0.062). The pouch calculi were detected in 2 cases (3.7), metabolic complication in 8 cases (14.8%), and uretero-intestinal anastomosis stricture in 6 cases (11.1%) in the Studer group. Y-pouch group exhibited uretero-intestinal anastosis stricture in 2 cases (5.6%) without pouch calculi and metabolic complications.The perioperative and histopathological data of the patients were stratified according to the neobladder surgical technique used and are summarized in Table p = 0.96). The achieved mean capacity of the Y-pouch neobladder at the 12-month follow-up was 417.2 (± 30.6) ml, which is not significantly different compared to that of the Studer neobladder 428.9 (± 25) ml (p = 0.169).Continence usually improved over time, and continence recovery within a mean of 6 months postoperatively range 1–12 months) was observed in most patients, irrespective of the surgical technique that was used. Moreover, according to Table  months wP = 0.0049) .Finally, we evaluated the renal function by monitoring serum creatinine level and the estimated glomerular filtration rate (eGFR) preoperatively and at each follow-up visit until the completion of 12 months postoperatively. The serum creatinine value fluctuations at follow-up visits of all the patients according to the technique used are shown in Fig. 49) Fig. A. Intere49) Fig. B. We als2O, range 28–52 for the Studer group and mean of 33 ml/cm H2O, range 30–43 for Y pouch), and most patients had > 30 ml/cm H2O compliance (80/90 patients). Urinary incontinence on provocative testing  was noted in each group with a mean ALPP of 52 cm H2O in the Studer group and 50 cm H2O in the Y-pouch group. Follow-up at 1 year had been completed by all patients (100%) in both groups  and the Y-pouch neobladder group 18/36). The mean preurodynamic PVR was 46 mL (range 0–90 mL) in the Studer neobladder and 20 mL in the Y-pouch technique. None of these patients exhibited detrusor (neobladder) overactivity during the cystometry filling phase. The average compliance of both groups was normal  receiving the Y-pouch technique and 4 patients (14.8%) receiving the Studer technique required additional endoscopic treatment. A uretero-neobladder anastomosis was not found in any of the patients (0%) that underwent the Y-pouch technique; however, 1 patient that underwent the standard technique (3.7%) experienced this complication and was treated with additional open surgery. In our study, we observed a significant difference in the need for cystostomy between patients who underwent the Studer neobladder procedure and those who had the Y-pouch neobladder technique. The Studer neobladder, which involves constructing a reservoir using a longer segment of the ileum, often leads to increased mucus production, necessitating the use of cystostomy as an alternative method for urinary drainage. However, it is important to note that many centers do not utilize cystostomy after Studer pouch construction, which challenges the advantage previously suggested for the Y-pouch neobladder technique, and it is crucial to reevaluate the advantages of the Y-pouch neobladder. Although the absence of cystostomy in patients with the Y-pouch neobladder may not be a distinct advantage, it could still contribute to improved patient comfort and satisfaction. Furthermore, it is plausible that the lack of cystostomy in Y-pouch neobladder patients may have a favorable impact on postoperative urinary function and continence outcomes, without increasing the risk of inadequate drainage complications.Metabolic acidosis occurring in the postoperative period and detected during the follow-up have been reported by several studies , 8; for Our hypothesis is explained by the lower urinary contact area of the small bowel. Theoretically, a smaller urinary contact area in the small bowel segment of the Y-pouch neobladder might result in a reduced urine absorption and also by less mucus production from this technique, and it has been suggested that the Y-pouch neobladder technique may lead to less mucus production compared to Studer approaches.Moreover, patients with bladder substitution achieved daytime control more rapidly than those who underwent a radical prostatectomy, and stress urinary incontinence was reported rarely. Additionally, it mentions that stress urinary incontinence  was rarely reported in the context of bladder substitution . Also, oThe rate of outlet obstruction by local recurrence was 2%, that of gross hematuria 1%, and that of entero-reservoir fistulas 1–2%. Daytime continence at 12 months was 92%, while nighttime continence was lower around 80%. Transient or permanent urinary retention was seen in 11–12% of male patients. In both series, long-term upper urinary tract safety was good. The risk of stenoses of the uretero-intestinal anastomosis with consecutive loss of renal function decreased with the introduction of non-refluxing implantation techniques. The rate of long-term metabolic complications remains low when adequate substitution with sodium bicarbonate is guaranteed in patients with impaired renal function. Patient selection and meticulous postoperative follow-up contributed to achieve good long-term results after cystectomy and orthotopic ileal neobladder substitution of the two large series of patients from the Universities of Ulm and Bern .The current study analyzed the urodynamic findings of patients who underwent RC with ONB using a Y-shaped reconstruction compared to the Studer neobladder. The main findings were that Y-shaped neobladders met the requirement of a reservoir with high capacity, low pressure, appropriate voiding, and preservation of renal function compared to the Studer technique.2O for non-neurogenic bladder) [2O values > 12.5–30 ml/cm represent the lower limit of normal. Our patients in this cohort study had UDS outcomes similar to those with a Studer neobladder in our study and other studies in terms of compliance and capacity [Qmax > 10 ml/s) with low PVR in most of the patients, suggesting satisfactory bladder emptying. There were some patients who need clean intermittent-self catheterization as compared to other reports with the rate ranging from 0 to 20% [To date, there are no standard urodynamic values for the ileal neobladder. However, when compared to reference values of a native bladder in 50-year-old men, the urodynamic profile of our Y-shaped ICUD was consistent with a normo-capacity (300–600 ml) and normo-compliant bladder (low compliance less than 30 ml/cm Hbladder) . Althougcapacity –28, desp0 to 20% –32, but 0 to 20% , might bPouch calculi occurred in patients with stapled neobladders but were absent in those with hand-sewn pouches. The common symptom was gross hematuria, and the calculi, typically less than 1 cm in diameter, were detected using KUB system CT scans during follow-up. Transurethral endoscopic lithotripsy successfully treated the calculi without functional complications. Calcium oxalate was the stone component in all cases. Although stapled neobladders may increase the risk of pouch calculi, a previous study reported comparable rates of stone formation to hand-sewn neobladders. Intermittent self-catheterization was the only variable predicting stone formation. We understand that the management of pouch calculi can vary depending on factors such as the size, composition, and location of the calculi. Surgical removal may be necessary in some cases, while preventive measures such as maintaining appropriate hydration, implementing dietary modifications, and regular surveillance may help minimize the risk of pouch calculi formation . FurtherHowever, there were some limitations of this study. It was a retrospective study that employed a small sample size of 36 patients who received the Y-pouch compared with the 54 patients who received the Studer neobladder. We also failed to present any long-term results (the follow-up period ended at 12 months postoperatively). However, the functional results and postoperative complication rate in the initial period associated with this technique were acceptable, and the trend of renal function parameters after an RC appeared better than that of the Studer technique. Future studies should include a larger number of patients and employ a prospective design to overcome the existing limitations. The Studer procedure and the Y-pouch technique presented in this study provide comparable perioperative outcomes in patients undergoing radical cystectomy with an ONB, at both the early and mid-term assessments. The Y-shaped neobladder meets the requirement of a reservoir with high capacity, low pressure, appropriate voiding, and preservation of renal function. Therefore, we propose the Y-pouch neobladder to be one of the alternative ileal neobladder techniques to the Studer neobladder. No questionnaires were used for sexual function or incontinence. Further prospective, randomized, controlled, comparative studies are needed to confirm its efficacy.Our study presented an efficacious Y-pouch technique for the surgical construction of an ONB with a complication rate as well as outcomes comparable to those of the standard Studer technique. In addition, the Y pouch is a technically easier procedure to perform than the Studer technique and is equally safe. The Y-pouch ileal neobladder is feasible and safe for use as the standard neobladder technique for urinary diversion in patients with bladder cancer undergoing radical cystectomy.


Malnutrition is widely known to affect growth in children. There are many studies focusing on malnutrition globally in relation to limited food access; however, there is only limited research on disease-related malnutrition, especially in chronic conditions and particularly in developing countries. This study aims to review articles on the measurement of malnutrition in pediatric chronic disease, especially in developing countries where there are resource limitations in identifying nutritional status in pediatric chronic disease with complex conditions. This state-of-the-art narrative review was conducted through search of literatures through 2 databases, and identified 31 eligible articles published from 1990 to 2021. This study found no uniformity in malnutrition definitions and no consensus regarding screening tools for the identification of the malnutrition risk in these children. In developing countries where resources are limited, instead of focusing on finding the best tools to identify the malnutrition risk, the approach should be directed toward developing systems that work best according to capacity and allow for a combination of anthropometry assessment, clinical evaluation, and observation of feeding access and tolerance on a regular basis. Pediatric malnutrition is an ongoing burden in developing countries, particularly in Southern Asia, as compared with Latin America and the northern and western regions of Africa. It is globally known to be the most crucial risk factor for morbidity and mortality . ApproxiThe first type of malnutrition occurs in relation to environmental factors, such as limited food access or decreased dietary intake, which results in an imbalance relative to nutritional needs, thereby affecting growth, development, and other health aspects. Disease-related malnutrition may progress to acute or chronic disease and occurs because of an energy imbalance due to increased catabolism, decreased appetite, or increased energy losses, which also have detrimental effects on the outcomes ,4.Studies have clearly observed that disease-related malnutrition is associated with an increase in the length of stay of hospitalized children and additional financial burdens. A study in the Netherlands noted the annual medical costs for the country, estimated at €80 million for disease-related malnutrition, which equals 5.5% of the total hospital costs for these hospitalized children ,7.The causes of malnutrition in children with chronic disease are multifactorial and are associated with the underlying disease; thus, careful assessment and management are required for chronic disease.This study observed the most common chronic diseases in children, such as congenital heart disease (CHD), chronic kidney disease (CKD), chronic liver disease (CLD), and malignancy, in which their nutritional assessment may be complicated with preceding conditions such as feeding intolerance, water retention, peripheral edema, electrolyte disturbance, tumor masses, and decreases in bone density and fat mass . IndonesOur research focused on chronic malnutrition in children with chronic diseases as mentioned above, which has received less attention in developing countries than that on malnutrition caused by infectious diseases. The combination of anthropometry assessment, clinical evaluation, observation on feeding tolerance, and biochemistry analysis should be conducted on a regular basis to ensure adequate nutrition. Lack of uniform definitions, heterogenous screening practices, and the failure to recognize nutrition as part of crucial patient care, however, have contributed to underrecognition of the prevalence of malnutrition in relation to its outcomes ,4. In deThe initial concept of the study was derived from an expert meeting that consisted of 6 child health professionals, who contributed input and presented current challenges in managing malnutrition in chronically ill children. The purpose of this study was to review articles available on the measurement of malnutrition in pediatric chronic disease, especially in developing countries where resource limitations restrict identification of the nutritional status in pediatric chronic disease with complex conditions.This is a state-of-the-art narrative review conducted through search of literatures on the measurement of malnutrition in pediatric chronic diseases. There are 5 domains included in the overall setup of the definition: anthropometrics, screening tools, etiology, chronicity, and impact on functional status and its management. These domains were used to evaluate and explore the implications of malnutrition in chronic disease.To identify articles published on disease-related malnutrition in pediatric chronic disease, we conducted keyword searches in PubMed and PubMed Central (PMC). The literature search was conducted from July 2021 to August 2021.For PubMed, we applied the following MeSH terms: “Malnutrition”[Mesh] OR “Child Nutrition Disorders”[Mesh] OR “Infant Nutrition Disorders”[Mesh]. We limited our search to papers published in or after the year 1990 to achieve certain relevancy to socioeconomics, available diagnosis tools, and management. For PMC, we used the following search terms on papers published from 1990 to 2021 for all MEDLINE journals: “pediatrics”[All Fields] AND “malnutrition”[All Fields] AND “chronic disease”[All Fields]. We did not limit the last search with MeSH terms to ensure that we have included recent papers that were not yet indexed, and may not miss any synonym in terminology that maybe relevant to our research questions.•Study site: Studies conducted in various countries at any level can be outpatient or inpatient settings.•Design: Randomized and nonrandomized controlled trials and observational studies.•Outcome: Disease-related malnutrition in children at any age between 0 and 18 y with chronic disease.•Relevance: Studies published that addressed any factors identified in the ASPEN framework.The following inclusion criteria were applied during our search of literatures:P values less than or equal to 0.05 and 95% CIs.For observational studies, we included variables depending on the available data and statistical methods. Statistical associations reported are considered significant, with Articles not published in English, published before 1990, and articles not available for free in full texts were excluded from this narrative review. The PRISMA flow diagram containing details of article selection process is presented in We acquired a total of 1063 articles from searches using the aforementioned search terms. Of the 1063 articles found, we excluded 1025 articles after screening based on the titles and abstracts, resulting in 38 eligible articles. Another 7 articles were further excluded because of the fact that these articles were available only as abstracts, resulting in a total of 31 full-text articles reviewed.These articles were reviewed using the aforementioned 5 domains to establish a better framework for the understanding of disease-related malnutrition . As malnPediatric patients with chronic disease have been known to be an increased risk of malnutrition, which leads to poor outcomes. Anthropometric assessment can be challenging in this group when the disease and nutritional status have a reciprocal effect. Additionally, malnutrition in chronic disease is also complicated by changes in the body composition such fat mass, fat-free mass, and total-body water . RegularThe American Society of Parenteral and Enteral Nutrition (ASPEN), under the WHO guidelines, recommended that anthropometric measurements should be expressed as Z-scores. Mild malnutrition was defined with Z-scores of −1 to −1.9, whereas moderate malnutrition was defined with a Z-score between −2 and −2.9 and severe malnutrition was defined with a Z-score of <−3. Furthermore, the consensus also endorsed the use of weight-for-height (WFH), BMI, or height-for-age Z-score (HAZ) in the WHO’s child growth standards from birth to the age of 2 y, and the CDC growth charts for children of ages 2–20 y . Some coAdjusted measurements and careful interpretation are needed for malnourished children with chronic disease, because the nutrition status is compromised by complex conditions, such as decreases in bone density, organomegaly, or water retention. This review observed studies on chronic diseases in children that are mostly known to be related to challenges in malnutrition due to altered body composition: chronic heart, kidney, liver disease, and malignancy.P < 0.001, t-test). Although the study did not specify the cut-off age for measuring the head circumference, it observed that all of the above measurements, except the head circumference, differed significantly from the healthy standard .TAB.TAB46].TMeanwhile, in CKD, malnutrition may worsen kidney disease and the glomerular filtration rate, which increases the risk of progression to end-stage renal disease and the start of peritoneal dialysis at a younger age. Additionally, a longer duration of dialysis is also associated with increased malnutrition . The recThe typical diet for CKD should be include a restricted potassium intake of 40–120 mg/kg/d for infants and younger children, that of 30–40 mg/kg/d for older children, and a restricted sodium intake of 1500–2400 mg/d along with regular urine analysis and the timely introduction of transplant or dialysis service . It has CLD with malnutrition enhances the susceptibility to infection and increases morbidity and mortality risks. Due to malnutrition, patients suffer from diarrhea, bleeding, or bone disease. These also affect the outcomes of liver transplantation . ChildreIn addition, undernourishment in children with cancer reduces immunocompetence and causes delayed wound healing, decreased survival rates, prolonged hospital stays, increased risk of readmission, and reduced quality of life . NutritiManagement should then be individualized according to each response. Breastmilk is optimal for infants with cancer, and if required, high-energy protein formulas can be offered to increase calorie density.A balanced diet with adequate protein and high-energy levels is essential to avoid excessive carbohydrate and fat consumption, as noticed in children with cancer .Consistent evidence suggests that Indonesia, like other developing countries, is very vulnerable to nondisease (or nonillness)–related malnutrition . HoweverIn the literature review, we found some challenges in identifying malnutrition in chronic disease. First, we found that there was a lack of a uniform definition of malnutrition as a result of chronic disease, which made the literature search challenging. We retrieved articles that focused on nutrition-related chronic disease (such as diabetes and hypertension) and disease-related malnutrition while some centers used the term “illness-related malnutrition.”Second, although the consensus regarding the definition of disease-related malnutrition requires a 3-mo duration ,34 and iFor anthropometric parameters, in conditions such as CKD, CHD, CLD, and malignancy with altered body composition, some adjustments need to be made in choosing the right measurement. In hospitals where DXA is not readily available, the measurement can be performed with the closest anthropometry parameters based on studies that compared DXA using standardized protocols. For example, a study observed that the MUAC can provide a good estimate of lean body mass as measured by DXA in identifying the malnutrition risk in children with cancer .There are several clinical tools developed for the identification of children at the risk of malnutrition, yet thus far, there is no consensus on the ideal screening tool to determine malnutrition risk in pediatric patients with chronic disease and there is no agreement between the screening tools. There are, thus far, no gold-standard methods for nutritional risk assessment. One way to consider the screening tools, especially in developing countries, is by checking their applicability in each hospital. The ease or difficulty of implementing each of these screening tools can be determined according to the availability of the healthcare team. PYMS and STAMP were, for example, developed for nurses; STRONGkids, on the other hand, has 2 questions that need to be answered by parents and the other 2 by healthcare professionals  . MoreoveA study by Poulimeneas et al.  also higUltimately, however, the applicability of anthropometric measurements and screening tools needs to be assessed by each center according to their feasibility.In developing countries, the prevalence of disease-related malnutrition in pediatric patients may be underestimated, especially in those with pre-existing malnutrition prior to disease development. The best screening tool for the identification of malnutrition risk is the one that is most applicable in each health unit inasmuch as there is systematic nutritional screening with regular follow-ups to identify the malnutrition risk in both inpatient and outpatient settings.Nutrition is unquestionably a crucial aspect in children with chronic disease. It would be beneficial for tertiary hospitals to have a good network system with primary health care; thus, evaluation and regular nutritional assessment can be regularly and continuously evaluated. Although there is no uniform definition of malnutrition nor a consensus regarding screening tools, hospitals in developing countries need to focus on screening systems, professional teams, and management that work best according to the hospital’s own capacity.The authors’ responsibilities were as follows – YD, NN, RBK, BS, MA, IGLS: conceptualized and designed the study and critically revised the manuscript; MP, YD, NN, RBK, BS, MA, IGLS: acquired and analyzed the literatures used and drafted the manuscript; NLS, RB: critically revised the manuscript and provided final approval; and all authors: read and approved the final version of the manuscript.MP, YD, NN, RBK, BS, MA, and IGLS, no conflicts of interest. NLS and RWB, employees of Danone Specialized Nutrition Indonesia.The authors received no specific funding for this work.Data described in the manuscript will be made available pending application and approval.