Measurement of physical activity and frailty in the early post-operative period after kidney transplant: Single-center prospective pilot study using Fitbit watch

Background: Physical activity monitors (PAMs) allow patients to track multiple health parameters and may be helpful tools to assess patient’s physical recovery after kidney transplant (KT). We performed a pilot study to quantify early postoperative physical activity after KT. Methods: Adult KT candidates were screened prospectively for inclusion and provided with a PAM (Fitbit® Inspire 2) for the first 30 days after KT. Patients who did not speak English and had undergone multi-organ transplants were excluded. Several frailty tests were performed prior to KT and on post-operative day 30: Fried Frailty Phenotype and 6-minute walk test. Results: 14 patients were enrolled since February 2021 with baseline characteristics described in Table 1. There was a significant difference in the average daily steps during the 1st week compared to the 4th week after KT (Week 1: 3200 steps vs. Week 4: 6978 steps, p\u3c0.001). The number of steps during the first 30 days after KT correlated negatively with hospital length of stay (r -0.53,p=0.02). There was no difference in the average daily steps between pre-frail and non-frail patients [Figure 1A]. Having a post-operative complication (Clavien grade 1-3: n=5) significantly dropped the average daily steps for the first 30 days after KT (complication 6811 steps [SD 2810] vs. no-complication 2275 steps [SD 740];p=0.009) [Figure 1B]. Conclusion: PAM effectively captures post-operative biophysical parameters and can be successfully implemented to monitor patient’s recovery after KT

Measurement of physical activity and frailty in the early post-operative period after kidney transplant; Single-center prospective pilot study using Fitbit watch

Background: Physical activity monitors (PAMs) allow patients to track multiple health parameters and may be helpful tools to assess patient’s physical recovery after kidney transplant (KT). We performed a pilot study to quantify early postoperative physical activity after KT. Methods: Adult KT candidates were screened prospectively for inclusion and provided with a PAM (Fitbit® Inspire 2) for the first 30 days after KT. Patients who did not speak English and had undergone multi-organ transplants were excluded. Several frailty tests were performed prior to KT and on post-operative day 30: Fried Frailty Phenotype and 6-minute walk test. Results: 14 patients were enrolled since February 2021 with baseline characteristics described in Table 1. There was a significant difference in the average daily steps during the 1st week compared to the 4th week after KT (Week 1: 3200 steps vs. Week 4: 6978 steps, p\u3c0.001). The number of steps during the first 30 days after KT correlated negatively with hospital length of stay (r -0.53,p=0.02). There was no difference in the average daily steps between pre-frail and non-frail patients [Figure 1A]. Having a post-operative complication (Clavien grade 1-3: n=5) significantly dropped the average daily steps for the first 30 days after KT (complication 6811 steps [SD 2810] vs. no-complication 2275 steps [SD 740];p=0.009) [Figure 1B]. Conclusion: PAM effectively captures post-operative biophysical parameters and can be successfully implemented to monitor patient’s recovery after KT

Design, Green Synthesis and Tailoring of Vitamin E TPGS Augmented Niosomal Nano-Carrier of Pyrazolopyrimidines as Potential Anti-Liver and Breast Cancer Agents with Accentuated Oral Bioavailability

VEGF plays a crucial role in cancer development, angiogenesis and progression, principally liver and breast cancer. It is vital to uncover novel chemical candidates of VEGFR inhibitors to develop more potent anti-breast and anti-liver cancer agents than the currently available candidates, sorafenib and regorafenib, that face resistance obstacles and severe side effects. Herein, nine pyrazolopyrimidine derivatives were designed, synthesized as sorafenib and regorafenib analogues and screened for their in vitro cytotoxic and growth inhibition activities against four human cancer cell lines, namely breast cancer (Michigan Cancer Foundation-7 (MCF-7), hepatocellular carcinoma (HCC) type (HepG2), lung carcinoma (A-549) and human colorectal carcinoma-116 (HCT-116)). Among the tested compounds, compounds 1, 2a, 4b and 7 showed the uppermost cytotoxic activities against all aforementioned cell lines with IC50 estimates varying from 6 to 50 µM, among which compound 7 showed the best inhibitory activity on all tested compounds. Stunningly, compound 7 showed the best significant inhibition of the VEGFR-2 protein expression level (72.3%) as compared to the control and even higher than that produced with sorafenib and regorafenib (70.4% and 55.6%, respectively). Modeling studies provided evidence for the possible interactions of the synthesized compounds with the key residues of the ATP binding sites on the hinge region and the “DFG out” motif of VEGFR-2 kinase. Collectively, our present study suggests that pyrazolopyrimidine derivatives are a novel class of anti-cancer drug candidates to inhibit VEGF-VEGFR function. Aspiring to promote constrained aqueous solubility, hence poor oral bioavailability of the developed lead molecule, 7 and 2a-charged D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) surface-coated niosomes were successfully constructed, adopting a thin film hydration technique striving to overcome these pitfalls. A 23 full factorial design was involved in order to investigate the influence of formulation variables: type of surfactant, either Span 60 or Span 40; surfactant:cholesterol ratio (8:2 or 5:5) along with the amount of TPGS (25 mg or 50 mg) on the characteristics of the nanosystem. F2 and S2 were picked as the optimum formula for compounds 2a and 7 with desirability values of 0.907 and 0.903, respectively. In addition, a distinguished improvement was observed in the compound’s oral bioavailability and cytotoxic activity after being included in the nano-TPGS-coated niosomal system relative to the unformulated compound. The nano-TPGS-coated niosomal system increased the hepatocellular inhibitory activity four times fold of compound 7a (1.6 µM) and two-fold of 2a (3 µM) relative to the unformulated compounds (6 µM and 6.2 µM, respectively)

Melanocyte localization and distribution in human cholesteatoma

Olszewska E, Wagner M, Goon P, et al. Melanocyte localization and distribution in human cholesteatoma. Histology and Histopathology . 2008;23(3):291-296

Melanocyte localization and distribution in human cholesteatoma

Introduction: Melanocytes in skin are derived from the neural crest and colonize the epidermis in the first trimester of gestation. Melanocytes have been observed in the nasopharyngeal, inner ear and oral mucosa and should therefore be present in the middle ear mucosa. Aims: To identify and determine the distribution of melanocytes in human cholesteatoma and normal meatal skin in Caucasian adults. Material and methods: Human cholesteatoma (n=18) and normal meatal skin samples (n=10) were investigated immunohistochemically with anti-HMB-45 and MART- 1 antibodies. Localization and distribution of melanocytes were assessed in the epidermis and cholesteatoma using an automatic analyzing system. Results: Regular skin exhibited melanocytes within the epidermis and accounted for 10% of the total cell number. They occurred partly as membrane-bound clusters. Cholesteatoma matrix melanocytes were observed in the basal layer and exhibited an oval or roundmorphology. Decreased numbers of melanocytes in the basal layer correlated with keratinization within cholesteatoma samples. Melanocytes revealed monomorphous nuclei, abundant cytoplasm containing particles of melanin. Found adjacent to glands and blood vessels, melanocytes were also scattered among the mesenchymal cells. Accounting for 2-6% of the total cell number within the squamous epithelium, melanocyte density was significantly lower in cholesteatoma tissue than in skin. Conclusions: The melanocyte distribution pattern was different when comparing the epithelia of skin and cholesteatoma. The presence of melanocytes in cholesteatoma may be due to an ingrowth, consequently controlled by keratinocyte-derived signals. In terms of the pathogenesis of cholesteatoma, neither squamous metaplasia nor melanocyte metaplasia can be excluded by our data

Involvement of the α7-nicotinic acetylcholine receptors in the anti-inflammatory action of the thymulin-related peptide (PAT)

Background and Purpose: Peptide analog of thymulin (PAT) has been shown to have anti-hyperalgesic and anti-inflammatory properties in animal models of inflammation. Recent reports suggest that the peripheral cholinergic system has an anti-inflammatory role mediated by α7-nicotinic acetylcholine receptor (α7-nAChR). Our aim is to investigate whether the action of PAT is mediated, via the cholinergic pathway. Experimental Approach: The anti-hyperalgesic and anti-inflammatory action of PAT was assessed in rat models of inflammatory nociceptive hyperactivity (carrageenan and endotoxin) and in a mice air-pouch model for localized inflammation, respectively; the possible attenuation of PAT\u27s effects by pretreatment with the α7-nAchR specific antagonist methyllycaconitine citrate (MLA) was also investigated. In another series of experiments, using two electrode recordings, the effect of PAT on the α7-nAChRs, expressed in Xenopus Oocytes, was also determined. Key Results: Administration of PAT reversed inflammatory nociceptive hyperactivity and cold and tactile hyperactivity in rats. This effect was partially or totally prevented by MLA, as assessed by different behavioral pain tests. Treatment with PAT also reduced the alteration of cytokines and NGF levels by carrageenan injection in the mouse air pouch model; this effect was partially antagonized by MLA. Electrophysiological recording demonstrated that PAT significantly potentiated the α7-nAchR expressed in Xenopus Oocytes. These effects were not observed when a control peptide, with a reverse sequence (rPAT), was utilized. Conclusions and Implications: The behavioral and electrophysiological observations described in this report demonstrate that PAT mediates, at least partially, its anti-inflammatory action by potentiating the α7-nAChR. These results indicate that PAT has a potential for new therapeutic applications as anti-inflammatory and analgesic agent. © 2013 IBRO