Surgical patient registries: scoping study of challenges and solutions.

Patient surgical registries are essential tools for public health specialists, creating research opportunities through linkage of registry data with healthcare outcomes. However, little is known regarding data error sources in the management of surgical registries. In June 2022, we undertook a scoping study of the empirical literature including publications selected from the PUBMED and EMBASE databases. We selected 48 studies focussing on shared experiences centred around developing surgical patient registries. We identified seven types of data specific challenges, grouped in three categories- data capture, data analysis and result dissemination. Most studies underlined the risk for a high volume of missing data, non-uniform geographic representation, inclusion biases, inappropriate coding, as well as variations in analysis reporting and limitations related to the statistical analysis. Finally, to expand data usability, we discussed cost-effective ways of addressing these limitations, by citing aspects from the protocols followed by established exemplary registries.

The role of DNA demethylation in liver to pancreas transdifferentiation.

BACKGROUND: Insulin producing cells generated by liver cell transdifferentiation, could serve as an attractive source for regenerative medicine. The present study assesses the relationship between DNA methylation pTFs induced liver to pancreas transdifferentiation. RESULTS: The transdifferentiation process is associated with DNA demethylation, mainly at gene regulatory sites, and with increased expression of these genes. Active inhibition of DNA methylation promotes the pancreatic transcription factor-induced transdifferentiation process, supporting a causal role for DNA demethylation in this process. CONCLUSIONS: Transdifferentiation is associated with global DNA hypomethylation, and with increased expression of specific demethylated genes. A combination of epigenetic modulators may be used to increase chromatin accessibility of the pancreatic transcription factors, thus promoting the efficiency of the developmental process.

Antitumoral activity of 1,2,4-oxadiazoles compounds isolated from the Neowerdermannia vorwerkii in liver and colon human cancer cells.

Two unknown 1,2,4-oxadiazoles (3-(pyridin-3-yl)-5-(thiophen-3-yl)-1,2,4-oxadiazole and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole) and one known 1,2,4-oxadiazole (5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole) were isolated from tubers of Neowerdermannia vorwerkii, collected from the San Juan Huancollo, Ingavi province, La Paz, Bolivia. The chemical structures of these compounds were elucidated through NMR and HRMS spectroscopic analyses. All compounds showed apoptotic capacity against the SK-HEP-1 and Caco-2 tumour cells. 5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2, 4-oxadiazole showed slight apoptotic capacities, with an IC50 between 17.46 ± 0.75 to 15.91 ± 0.62 µM and 39.29 ± 0.98 to 34.81 ± 0.70 µM, respectively. 3-(pyridin-3-yl)-5-(thiophen-3-yl)-1,2,4-oxadiazole showed a higher apoptotic capacity with an IC50 in the range of 0.98 ± 0.11 to 0.76 ± 0.03 µM, similar to that of the positive control (Dimethylenastron).

Anti-inflammatory properties of Neowerdermannia vorwerkii Fric 'Achacana' used in treating stomach-related ailments.

ETHNO-PHARMACOLOGICAL RELEVANCE: The tuber of Neowerdermannia vorwerkii commonly known as 'Achacana' is used as an infusion in Andean countries to treat various gastrointestinal ailments, kidney and liver diseases. AIM OF THE STUDY: This study determined the anti-inflammatory activity of the aqueous extract from Neowerdermannia vorwerkii and identified the compounds related to this activity. MATERIALS AND METHODS: A bio-guided isolation of the active compounds of Neowerdermannia vorwerkii was carried out, selecting the sub-extracts and fractions depending on their anti-inflammatory activity in the Hs 738.St/Int, Hs 746T and NCI-N87 cells. RESULTS: Three compounds were obtained and characterised by nuclear magnetic resonance and mass spectrometry. These compounds are (3-(pyridin-3-yl)-5-(tiophen-3-yl)-1,2,4-oxadiazole (1), 5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole (2) and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole (3). Regarding their anti-inflammatory activity, the three compounds inhibited the production of cytokines (IL-1ß, IL-6 and TNF-α), however, compound 1 was the most active, with an IC50 of 0.87 µM in all cell lines. CONCLUSION: In the present study, the anti-inflammatory activity of the aqueous extract of Neowerdermannia vorwerkii was tested and analysed, following the isolation of three 1,2,4-oxadiazoles type compounds with similar pharmacological properties.

Wound healing, anti-inflammatory and anti-melanogenic activities of ursane-type triterpenes from Semialarium mexicanum (Miers) Mennega.

ETHNO-PHARMACOLOGICAL RELEVANCE: The bark of Semialarium mexicanum commonly known as 'Cancerina' is used as an infusion in Central America and Mexico to treat various wound infections, as well as skin and vaginal ulcers. AIM OF THE STUDY: This study aimed to determine the wound healing, anti-inflammatory and anti-melanogenic activities of the aqueous extract of Semialarium mexicanum and to identify the compounds related to these activities. MATERIALS AND METHODS: A bio-guided isolation of the active compounds of Semialarium mexicanum was carried out, selecting the sub-extracts and fractions depending on their wound healing, anti-inflammatory and anti-melanogenic activities in the RAW 264.7, NIH/3T3 and B16-F10 cells. RESULTS: Three compounds were obtained and characterised by nuclear magnetic resonance and mass spectrometry. These compounds are (3ß)-3-Hydroxy-urs-12-en-28-oic acid (1), (3ß)-Urs-12-ene-3,28-diol (2) and (2α, 19α)-2,19-Dihydroxy-3-oxo-urs-12-en-28-oic acid (3). Regarding the anti-inflammatory activity, the three compounds inhibited the production of NF-κB and NO, however, compound 3 was the most active with IC50 values of 8.15-8.19 µM and 8.94-9.14 µM, respectively, in all cell lines. The anti-melanogenic activity of these compounds was evaluated by the inhibition of tyrosinase and melanin in the B16-F10 cell line. The three compounds showed anti-melanogenic activity, however, compound 3 was the most active with an IC50 of 8.03 µM for the inhibition of tyrosinase production, and an IC50 of 8.53 µM for the inhibition of melanin production. Finally, concerning the wound healing activity, the three compounds presented proliferative activity in all the tested cell lines, however, compound 3 showed higher cell proliferation percentages than compounds 1 and 2 (88.89-89.60% compared to 64.92-65.71% and 71.53-71.99%, respectively). CONCLUSION: The wound healing, anti-inflammatory and anti-melanogenic activity of the aqueous extract of Semialarium mexicanum was tested and analysed in the present study, after having isolated three ursane-type triterpenes.

Flow cytometry of bone marrow aspirates from neuroblastoma patients is a highly sensitive technique for quantification of low-level neuroblastoma.

Background: Bone marrow involvement is an important aspect of determining staging of disease and treatment for childhood neuroblastoma. Current standard of care relies on microscopic examination of bone marrow trephine biopsies and aspirates respectively, to define involvement. Flow cytometric analysis of disaggregated tumour cells, when using a panel of neuroblastoma specific markers, allows for potentially less subjective determination of the presence of tumour cells. Methods: A retrospective review of sequential bone marrow trephine biopsies and aspirates, performed at Great Ormond Street Hospital, London, between the years 2015 and 2018, was performed to assess whether the addition of flow cytometric analysis to these standard of care methods provided concordant or additional information. Results: There was good concurrence between all three methods for negative results 216/302 (72%). Positive results had a concordance of 52/86 (61%), comparing samples positive by flow cytometry and positive by either or both cytology and histology.  Of the remaining samples, 20/86 (23%) were positive by either or both cytology and histology, but negative by flow cytometry. Whereas 14/86 (16%) of samples were positive only by flow cytometry. Conclusions: Our review highlights the ongoing importance of expert cytological and histological assessment of bone marrow results. Flow cytometry is an objective, quantitative method to assess the level of bone marrow disease in aspirates.  In this study, flow cytometry identified low-level residual disease that was not detected by cytology or histology. The clinical significance of this low-level disease warrants further investigation.

Hydroalcoholic extract of Tagetes minuta L. inhibits inflammatory bowel disease through the activity of pheophytins on the NF-κB signalling pathway.

ETHNO-PHARMACOLOGICAL RELEVANCE: Species of the genus Tagetes are well known for their anti-inflammatory properties. Tagetes minuta "Huacatay" is an endemic species of South America that has been used in traditional medicine since ancient times as a remedy for stomach and intestinal discomfort. AIM OF THE STUDY: The aim of this study is to investigate the anti-inflammatory activity of the aqueous and hydroalcoholic extracts of the Huacatay, identifying the compounds responsible for this activity. MATERIALS AND METHODS: Anti-inflammatory activity of the compounds, fractions and extracts was evaluated in Hs 746T (stomach), HIEC-6 (intestine) and THP-1 (monocytes peripheral blood) cells by measuring their inhibitory capacity against the NF-κB production. RESULTS: Aqueous and hydroalcoholic extracts of Tagetes minuta displayed anti-inflammatory activity in vitro, the hydroalcoholic extract being the most active (IC50 between 59.72 and 66.42 µg/mL) in all cell lines. Bio-guided hydroalcoholic extract fractionation led to the isolation and characterisation of two pheophytins, pheophytin a (1) and 132-hydroxy pheophytin a (2). Both compounds inhibited the production of NF-κB with IC50 values in the low micromolar range, with an IC50 between 12.32 and 16.01 µM for compound 1 and 7.91-9.87 µM for compound 2. CONCLUSIONS: The two pheophytins isolated in this study inhibit the production of NF-κB, thus showing that the traditional anti-inflammatory use of Tagetes minuta can be proved through pharmacological assays. This contributes to understanding the anti-inflammatory activity of the Huacatay extracts and their use in the treatment of stomach and intestinal discomfort.

COVID-19 and diabetes mellitus: Unraveling the hypotheses that worsen the prognosis (Review).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the caused disease - coronavirus disease 2019 (COVID-19), has affected so far >6,000,000 people worldwide, with variable grades of severity, and has already inflicted >350,000 deaths. SARS-CoV-2 infection seems severely affected by background diseases such as diabetes mellitus and its related complications, that seem to be favoring the most severe manifestations of SARS-CoV-2 and, therefore, require special attention in clinical care units. The present literature review focus on addressing several hypotheses explaining why diabetic patients could develop multi-organ failure in severe acute respiratory syndrome coronavirus (SARS-CoV) infections. Undoubtedly, as diabetes related complications are present it is expected to emphasize the severity of the COVID-19. Dermatological complications can occur and worsen in diabetic patients, and diseases such as acanthosis nigricans and psoriasis are prone to more severe manifestations of COVID-19. Approaches to treat SARS-CoV-2 infected patients, based on different solutions i.e. plasma therapy, use of antiviral compounds, development of vaccines or new therapeutic agents are ongoing.

Alkaloids isolated from Tropaeolum tuberosum with cytotoxic activity and apoptotic capacity in tumour cell lines.

Two alkaloids were isolated and identified for the first time in the black tubers of Tropaeolum tuberosum, collected from the Titicani-Taca, Ingavi province in La Paz, Bolivia. Their structures were elucidated by extensive NMR and MS spectroscopic analyses. The isolated compounds were evaluated for their cytotoxicity and apoptotic capacity against four human cancer cell lines. 2-Benzyl-3-thioxohexahydropyrrolo[1,2-c]imidazole-1-one (1) showed slight cytotoxic activity against all the cancer cell lines which were tested, with IC50 values ranging from 27.45 ± 0.80 to 31.07 ± 0.87 µM. Moreover, N-(4-acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl) acetamide (2) showed significant anti-cancer potential, with IC50 values between 1.26 ± 0.57 µM and 1.37 ± 0.09 µM against all human cancer cell lines which were tested. Treatment of tumour cell lines with the compounds caused an increase in the apoptotic rate of these cells, observing that compound 2 presented an apoptotic effect which was double with respect to the control (Dimethylenastron).

Synthesis and biological screening of a library of macamides as TNF-α inhibitors.

Thirty-five macamide analogues were synthesised by modifying the initial molecular structure. The resulting structures were confirmed using NMR and MS. Cytotoxicity and the anti-inflammatory activity of these synthetic macamides were evaluated in the THP-1 cell line. Preliminary biological evaluation indicated that most of these synthetic macamides did not present cytotoxicity (MTT assay) in the tested cell line with respect to the control (actinomycin D). Regarding the anti-inflammatory activity, several analogues had a greater potential for inhibition of TNF-α than natural macamides. Synthetic macamide 4a was the most active (IC50 = 0.009 ± 0.001 µM) compared to the C87 (control). Through looking at the link between the chemical structure and the activity, our study proves that changes made to natural macamides at the level of the alkyl chain, the benzyl position, the amide bond, and the addition of two methyl groups to the aromatic ring (meta position) lead us to obtaining new macamides with greater anti-inflammatory activity.

Flavonoids of Tripodanthus acutifolius inhibit TNF-α production in LPS-activated THP-1 and B16-F10 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: T. acutifolius is an endemic species from South America which has been used in traditional medicine since ancient times due to its biological properties, including its anti-inflammatory effects. AIM OF THE STUDY: The aim of the article is to investigate the inhibitory activity of T. acutifolius over TNF-α production in THP-1 and B16-F10 cells. To achieve this, phytochemical analysis has been used to determine the compounds present in the species with anti-inflammatory effects. MATERIALS AND METHODS: Leaves and stems of T. acutifolius were extracted with n-heptane, dichloromethane, methanol and water. The resulting extracts were analysed in THP-1 and B16-F10 cells by measuring their inhibitory capacity over the production of TNF-α stimulated with LPS. RESULTS: The guided-bioassay led to the isolation of 6,2',4'-trimethoxyflavone (1), 5,3',4'-trihydroxy-6,7,8-trimethoxyflavone (2), (E)-2',4'-dihydroxy-6'-methoxy-chalcone (3) and 5,4'-dihydroxy-6,7,8-trimethoxyflavone (4) from the dichloromethanic extract. Compounds showed an inhibitory activity of TNF-⍺ production in THP-1 cells, with IC50 of 2.38 ±â€¯0.02 µM, 12.36 ±â€¯0.17 µM, 1.12 ±â€¯0.01 µM and 8.09 ±â€¯0.04 µM, respectively. In addition, the compounds showed an inhibitory activity of TNF-⍺ production in B16-F10 cells with IC50 of 1.32 ±â€¯0.03 µM, 5.63 ±â€¯0.09 µM, 0.60 ±â€¯0.02 µM and 3.77 ±â€¯0.15 µM, respectively. CONCLUSIONS: We identified 3 flavones (6,2',4'-trimethoxyflavone, 5,3',4'-trihydroxy-6,7,8-trimethoxyflavone, 5,4'-dihydroxy-6,7,8-trimethoxyflavone) and a chalcone ((E)-2',4'-dihydroxy-6'-methoxy-chalcone) present in the leaves and stems of T. acutifolius. These compounds are an alternative for the treatment of immune-mediated inflammatory disorders, acting as negative modulators over the TNF-α production.

Alkamides from Tropaeolum tuberosum inhibit inflammatory response induced by TNF-α and NF-κB.

ETHNO-PHARMACOLOGICAL RELEVANCE: Tropaeolum tuberosum, commonly known as "Mashua", is one of the plants most frequently used by Andean (Peruvian-Bolivian) people as food and medicine. It is used as a remedy against a wide range of diseases, especially those related with inflammation. OBJECTIVES: This study aims to identify compounds active against inflammatory related conditions. MATERIALS AND METHODS: A bioassay-guided isolation of anti-inflammatory compounds from black and purple tubers of T. tuberosum was performed measuring TNF-α and NF-κB production in THP-1 monocytic cells. RESULTS: The bioassay-guided isolation led to one active compound from purple T. tuberosum, N-oleoyldopamine (1), and another active compound from black T. tuberosum, N-(2-Hydroxyethyl)-7Z,10Z,13Z,16Z-docosatetraenamide (2). Both compounds displayed anti-TNF-α activity with IC50 values of 3.12 ±â€¯0.19 µM and 1.56 ±â€¯0.15 µM, respectively. Also, both compounds suppressed NF-κB with IC50 of 3.54 ±â€¯0.02 µM and 1.77 ±â€¯0.07 µM, respectively. CONCLUSIONS: We identified bioactive compounds from purple and black Tropaeolum tuberosum responsible for their anti-inflammatory activity: N-oleoyldopamine (1) and N-(2-Hydroxyethyl)-7Z,10Z,13Z,16Z-docosatetraenamide (2). This is the first report which isolates these compounds from T. tuberosum and describes their anti-inflammatory activities.