Antibiotic residues and microbial contamination in pasteurized whole milk intended for human consumption.

Background and Aim: Milk contamination for human consumption is one of the biggest concerns worldwide. To prevent milk contamination, it is important to implement sustainable production practices that ensure animal health and guarantee veterinary drugs have been used properly. This study aimed to detect antibiotic residues and microbial contamination in commercially available pasteurized whole milk intended for human consumption. Materials and Methods: We conducted a cross-sectional study on all brands of pasteurized milk (n = 17) for human consumption in Medellín, Colombia, from February 30 to April 30, 2022. Six milk samples of each brand were collected every 15 days, resulting in 102 samples. IDEXX SNAPduo™ ST Plus test (IDEXX Laboratories Inc, Maine, USA) was used to detect cephalosporins residues to detect beta-lactam and tetracyclines. We detected mesophilic aerobic bacteria and coliforms using Chromocult Coliform Agar® (Merck KGaA, Darmstadt, Germany) and Plate-Count Agar® (Merck KGaA), respectively. Results: Beta-lactam residues were found in 24.4% of the brands. No tetracyclines or cephalosporins were detected. Mesophilic aerobic bacteria and coliform contamination were detected in 42.6% and 12.8% of the brands, respectively. No fecal coliform contamination was detected. Conclusion: This study demonstrated the presence of antibiotic residues and microbial contamination in commercially available pasteurized whole milk intended for human consumption in the study area, highlighting its potential public health implications.

An evaluation of the cannabinoid content of the liquid and thermal degradation analysis of cannabis-labeled vape liquids.

Cannabidiol (CBD) vape pen usage has been on the rise given the changing political and scientific climate as well as the promotion of these delivery systems as a more accessible and lower-risk option for consumers. Despite being marketed as a safer way to use cannabis, CBD vape liquids are sold without restrictions or meticulous quality control procedures such as toxicological and clinical assessment, standards for product preservation, or investigative degradation analyses. Nine CBD-labeled vape liquid samples purchased and manufactured in the United States were evaluated and assessed for cannabinoid content. Quantification and validation of cannabinoids and matrix components was accomplished using gas and liquid chromatography with mass spectrometry analysis (GC-MS and LC-MS/MS) following liquid-liquid extraction with methanol. Samples degraded by temperature (analyzed by GC-MS) showed a greater disparity from the labeled CBD content compared with samples analyzed as purchased (by LC-MS/MS). Thermal degradation of the vape liquids showed increased levels of tetrahydrocannabinol (THC). Also, extended time and temperature degradation were evaluated in vape liquids by storing them for 15 months and then varying temperature conditions before analysis, which indicated CBD transformed into other cannabinoids leading to different cannabinoid content within the vape samples. Evaluation conducted on these vape liquids indicated the route of exposure, storage conditions, and length of storage could expose consumers to unintended cannabinoids and showed a concerning level of disagreement between the products' labeled cannabinoid content and the results generated by these analyses.

Water and mosquitoes as key components of the infective cycle of Francisella tularensis in Europe: a review.

Francisella tularensis is the pathogen of tularemia, a zoonotic disease that have a broad range of hosts. Its epidemiology is related to aquatic environments, particularly in the subspecies holarctica. In this review, we explore the role of water and mosquitoes in the epidemiology of Francisella in Europe. F. tularensis epidemiology has been linked to natural waters, where its persistence has been associated with biofilm and amebas. In Sweden and Finland, the European countries where most human cases have been reported, mosquito bites are a main route of transmission. F. tularensis is present in other European countries, but to date positive mosquitoes have not been found. Biofilm and amebas are potential sources of Francisella for mosquito larvae, however, mosquito vector capacity has not been demonstrated experimentally, with the need to be studied using local species to uncover a potential transmission adaptation. Transstadial, for persistence through life stages, and mechanical transmission, suggesting contaminated media as a source for infection, have been studied experimentally for mosquitoes, but their natural occurrence needs to be evaluated. It is important to clear up the role of different local mosquito species in the epidemiology of F. tularensis and their importance in all areas where tularemia is present.

Guided Imagery for Symptom Management of Patients with Life-Limiting Illnesses: A Systematic Review of Randomized Controlled Trials.

Background: Patients with life-limiting illnesses receiving palliative care have a high symptom burden that can be challenging to manage. Guided imagery (GI), a complementary and integrative therapy in which patients are induced to picture mental images with sensory components, has proven in quasi-experimental studies to be effective as a complementary therapy for symptom management. Objective: To systematically review randomized controlled trials that report evidence of guided imagery for symptom management in patients with life-limiting illnesses. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed for this review and the search strategy was applied in Medline, CINHAL, and Web of Science. The quality of articles was evaluated using the Cochrane Collaboration's Risk-of-Bias Tool 2 (RoB 2). The results are presented using the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews. Results: A total of 8822 studies were initially identified through the search strategy, but after applying exclusion criteria, 14 randomized controlled trials were included in this review. The quality assessment revealed that four studies had a high risk of bias, nine had some concerns, and one had a low risk of bias. Out of the 14 studies, 6 evaluated oncological diagnosis, while the remaining 8 focused on nononcological diagnoses across 6 different diseases. GI was found to be effective in managing symptoms in 10 out of the 14 studies. Regardless of the disease stage, patients who received guided imagery experienced relief from anxiety, depression, pain, sleep disturbances, and fatigue. Conclusion: GI therapy has shown promising results regarding symptom management in palliative care patients with life-limiting illnesses at different stages.

On the need of in vivo verifications as quality control for intraoperative electron radiotherapy in breast cancer.

INTRODUCTION: Intraoperative electron radiotherapy (IOERT) is a technique aiming to deliver radiotherapy during oncological surgery. In breast IOERT, the applicator and shielding disc placement are correlated with organs at risk (OAR) irradiation, in vivo verification of these parameters is scarcely reported. The aim of our study is to report and analyze possible causes of the misalignment using radiochromic films and compare our results to others reported in the bibliography. METHODS: From November 2019 to April 2023, in vivo verifications were performed for 33 patients. IOERT was performed using a LIAC 10 MeV (Sordina, Italy) electron accelerator. We attached a radiochromic film to the upper side of the polytetrafluoroethylene cover of the shielding disc. The percentage of the irradiation area outside the disc was recorded and various parameters (applicator angulations, prescription depth, tumor location and breast size) were analyzed to find possible correlations. RESULTS: For 29 patients, 20 Gy were prescribed while 10 Gy were prescribed to 4 patients. The average irradiated area outside the disc was 19% (0-56%) corresponding to a surface of 4.5 cm2 (0-17.4 cm2). The applicator of 5 cm was used for most of the patients. The mean prescription depth was 1.4 cm (0.5-2.5 cm). We found no correlation between the analyzed parameters and misalignment. CONCLUSION: This study confirms the presence and magnitude of the misalignments. We strongly recommend in vivo verifications as a quality check during IOERT procedures. The misalignment has no correlation with tumor localization parameters, so the solution could be based on technical improvements of the applicator.

Prevention and treatment of cisplatin-induced ototoxicity in adults: A systematic review.

OBJECTIVES: Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients. METHODS: Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales. RESULTS: Nineteen randomised controlled trials and five quasi-experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D-methionine) showed mild benefits in preventing cisplatin-induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention-related adverse effects, thereby limiting safety conclusions. CONCLUSIONS: Current interventions have mild benefits in preventing cisplatin-induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high-quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.

Treatment of metastatic squamous cell carcinoma arising in sacrococcygeal pilonidal sinus: a case report series.

Background: Squamous cell carcinoma (SCC) arising in a sacrococcygeal pilonidal sinus is rare, with cases of metastatic disease being even rarer. Among published cases, almost none have reported on systemic treatment. Objective: This disease has a poorer prognosis than other forms of cutaneous SCC; therefore, our objective is to shed some light on the treatment of metastatic disease. Methods: We present a series of nine cases treated at a single center, four of whom received systemic treatment. Additionally, other previously reported cases of metastatic disease are included in an attempt to draw stronger conclusions. Results: Four patients were treated under several treatment regimens, with a median progression-free survival of only 2 months and two instances of partial response (18%). The best result was achieved with cemiplimab. Across all the cases, there was a trend toward a benefit of the use of systemic treatment (HR 0.41, 95% CI 0.15-1.12, p = 0.083; median overall survival 13 vs. 8 months). Limitations: Limitations include the significant lack of information on previously published cases and the extremely heterogeneous nature of the existing information. Conclusion: The initial systemic treatment should be an anti-PD-1, as with other SCCs. After progression on anti-PD-1, there is no strong evidence to support the recommendation of a specific treatment or sequence: options include cetuximab and/or chemotherapy (platinum, paclitaxel, 5-fluorouracyl).

Breast metastases from non-primary breast malignancies: What should we know?

BACKGROUND: Metastases from extramammary malignant neoplasms are very rare, accounting for less than 2% of all breast malignancies. OBJECTIVE: The aim of this study is to describe the clinicopathological features and prognosis of breast metastases from non-primary breast malignancies at our institution. METHODS: We performed a retrospective observational study, obtaining data from electronic medical records and pathology databases between January 1985 and December 2020 for patients diagnosed with breast metastasis from non-primary breast malignancies. Only patients diagnosed by biopsy were included. RESULTS: Fifteen patients diagnosed with breast metastases from non-primary breast malignancies were included, 13 women (86,67%) and 2 men (13,33%). The median age at time of initial diagnosis was 56 years (IQR 21-68). The most frequent primary malignancy was melanoma (9/15; 60%). The median time to diagnosis of breast metastases was 65 months (IQR 13-106). The most common diagnostic modality was CT-scan (10/15; 66,67%). The median follow-up was 96 months (IQR 29-136). Eight patients underwent surgery (53,3%), being the most common surgical intervention breast-conserving surgery (5/8; 62,5%). Mortality at the end of follow-up was 53,3% (8/15). On the survival analysis, we found no differences between patients undergoing surgery and those only receiving systemic treatment [41,5 months (IQR 17,5-57,5) versus 14 months (IQR 2-24), respectively; p = 0,161]. CONCLUSIONS: Breast metastases from non-primary breast malignancies are extremely rare and represent a diagnostic and therapeutic challenge, due to the poor prognosis of these patients. Thus, arriving at the correct diagnosis is crucial to avoid unnecessary treatment in this population.

The Gram-positive bacterium Romboutsia ilealis harbors a polysaccharide synthase that can produce (1,3;1,4)-ß-D-glucans.

(1,3;1,4)-ß-D-Glucans are widely distributed in the cell walls of grasses (family Poaceae) and closely related families, as well as some other vascular plants. Additionally, they have been found in other organisms, including fungi, lichens, brown algae, charophycean green algae, and the bacterium Sinorhizobium meliloti. Only three members of the Cellulose Synthase-Like (CSL) genes in the families CSLF, CSLH, and CSLJ are implicated in (1,3;1,4)-ß-D-glucan biosynthesis in grasses. Little is known about the enzymes responsible for synthesizing (1,3;1,4)-ß-D-glucans outside the grasses. In the present study, we report the presence of (1,3;1,4)-ß-D-glucans in the exopolysaccharides of the Gram-positive bacterium Romboutsia ilealis CRIBT. We also report that RiGT2 is the candidate gene of R. ilealis that encodes (1,3;1,4)-ß-D-glucan synthase. RiGT2 has conserved glycosyltransferase family 2 (GT2) motifs, including D, D, D, QXXRW, and a C-terminal PilZ domain that resembles the C-terminal domain of bacteria cellulose synthase, BcsA. Using a direct gain-of-function approach, we insert RiGT2 into Saccharomyces cerevisiae, and (1,3;1,4)-ß-D-glucans are produced with structures similar to those of the (1,3;1,4)-ß-D-glucans of the lichen Cetraria islandica. Phylogenetic analysis reveals that putative (1,3;1,4)-ß-D-glucan synthase candidate genes in several other bacterial species support the finding of (1,3;1,4)-ß-D-glucans in these species.

125I Radioactive Seed Localization vs. Conventional Surgery for the Treatment of Mesenchymal Tumours: A Propensity Score Matching Analysis.

PURPOSE: Radioguided localization can assist the surgery of hard-to-find lesions. The aim was to evaluate the results of the 125I Radioactive Seed Localization (RSL) technique to guide a margin-free tumoral resection of mesenchymal tumours compared to conventional surgery and its influence in oncological outcomes. METHODS: Retrospective observational study of all consecutive patients who underwent 125I RSL for the surgery of a mesenchymal tumour from January 2012 to January 2020 in a tertiary referral centre in Spain. The control group was formed by patients with conventional surgery in the same period and centre. A Propensity Score matching at 1:4 ratio selected the cases for analysis. RESULTS: A total of 10 lesions excised in 8 radioguided surgeries were compared to 40 lesions excised in 40 conventional surgeries, with equal proportion of histological subtypes in each group. There was a higher proportion of recurrent tumours in the RSL group (80 % [8/10] vs. 27.5 % [11/40]; p: 0.004). An R0 was achieved in 80 % (8/10) of the RSL group and 65 % (26/40) of the conventional surgery group. The R1 rate was 0 % and 15 % (6/40), and the R2 rate was 20 % (2/10 and 8/40) in the RSL group and conventional surgery group, respectively (p: 0.569). No differences were detected in disease-free or overall survival between the different histological subtypes in the subgroup analysis. CONCLUSION: The 125I RSL technique of a challenging sample of mesenchymal tumours achieved a similar margin-free tumoral resection and oncological outcomes as conventional surgery.

Cell Wall Carbohydrate Dynamics during the Differentiation of Infection Structures by the Apple Scab Fungus, Venturia inaequalis.

Scab, caused by the biotrophic fungal pathogen Venturia inaequalis, is the most economically important disease of apples. During infection, V. inaequalis colonizes the subcuticular host environment, where it develops specialized infection structures called runner hyphae and stromata. These structures are thought to be involved in nutrient acquisition and effector (virulence factor) delivery, but also give rise to conidia that further the infection cycle. Despite their importance, very little is known about how these structures are differentiated. Likewise, nothing is known about how these structures are protected from host defenses or recognition by the host immune system. To better understand these processes, we first performed a glycosidic linkage analysis of sporulating tubular hyphae from V. inaequalis developed in culture. This analysis revealed that the V. inaequalis cell wall is mostly composed of glucans (44%) and mannans (37%), whereas chitin represents a much smaller proportion (4%). Next, we used transcriptomics and confocal laser scanning microscopy to provide insights into the cell wall carbohydrate composition of runner hyphae and stromata. These analyses revealed that, during subcuticular host colonization, genes of V. inaequalis putatively associated with the biosynthesis of immunogenic carbohydrates, such as chitin and ß-1,6-glucan, are downregulated relative to growth in culture, while on the surface of runner hyphae and stromata, chitin is deacetylated to the less-immunogenic carbohydrate chitosan. These changes are anticipated to enable the subcuticular differentiation of runner hyphae and stromata by V. inaequalis, as well as to protect these structures from host defenses and recognition by the host immune system. IMPORTANCE Plant-pathogenic fungi are a major threat to food security. Among these are subcuticular pathogens, which often cause latent asymptomatic infections, making them difficult to control. A key feature of these pathogens is their ability to differentiate specialized subcuticular infection structures that, to date, remain largely understudied. This is typified by Venturia inaequalis, which causes scab, the most economically important disease of apples. In this study, we show that, during subcuticular host colonization, V. inaequalis downregulates genes associated with the biosynthesis of two immunogenic cell wall carbohydrates, chitin and ß-1,6-glucan, and coats its subcuticular infection structures with a less-immunogenic carbohydrate, chitosan. These changes are anticipated to enable host colonization by V. inaequalis and provide a foundation for understanding subcuticular host colonization by other plant-pathogenic fungi. Such an understanding is important, as it may inform the development of novel control strategies against subcuticular plant-pathogenic fungi.

Radioguided surgery of mesenchymal tumors with 125I seeds.

INTRODUCTION: Radioguided surgery uses radioactive substances to identify and remove hard-to-locate lesions. Mesenchymal tumors constitute a heterogeneous group of neoplasms derived from the mesoderm, including benign lesions and malignant sarcomas. The aim of this study was to evaluate the ability of 125I radioactive seeds to guide intraoperative localization of mesenchymal tumors, analyzing the complication rates and evaluating the margins of the surgical specimens retrieved. METHODS: Retrospective observational study of all consecutive patients undergoing radioguided surgery of a mesenchymal tumor with a 125I radioactive seed from January 2012 to January 2020 at a tertiary referral center in Spain. The seed was inserted percutaneously guided by ultrasound or computed tomography in an outpatient setting. RESULTS: Fifteen lesions were resected in 11 interventions in 11 patients, recovering all lesions marked (100%) with a 125I seed. The lesions included areas of benign fibrosis (26.7%), cellular angiofibroma (6.7%), desmoid tumor (20%), solitary fibrous tumor (13.3%), chondrosarcoma (6.7%), and pleomorphic sarcoma (26.7%), with a high rate of recurrent tumors (60%). There was only one complication (6.7%) due to the seed falling within the surgical bed. According to the UICC classification of residual tumors, 80% of the lesions resulted in an R0 resection, 6.7% were R1 resections, and 13.3% were R2 resections. CONCLUSION: Radioguided surgery is an accurate technique for the resection of hard-to-locate mesenchymal tumors.

Comparative effectiveness of adding delamanid to a multidrug-resistant tuberculosis regimen comprised of three drugs likely to be effective.

Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and Phase III randomized controlled trial results. The Phase IIb trial found that the addition of delamanid to a background regimen hastened culture conversion; the results of the Phase III trial were equivocal. We evaluated the effect of adding delamanid for 24 weeks to three-drug MDR/RR-TB regimens on two- and six-month culture conversion in the endTB observational study. We used pooled logistic regression to estimate the observational analogue of the intention-to-treat effect (aITT) adjusting for baseline confounders and to estimate the observational analogue of the per-protocol effect (aPP) using inverse probability of censoring weighting to control for time-varying confounding. At treatment initiation, 362 patients received three likely effective drugs (delamanid-free) or three likely effective drugs plus delamanid (delamanid-containing). Over 80% of patients received two to three Group A drugs (bedaquiline, linezolid, moxifloxacin/levofloxacin) in their regimen. We found no evidence the addition of delamanid to a three-drug regimen increased two-month (aITT relative risk: 0.90 (95% CI: 0.73-1.11), aPP relative risk: 0.89 (95% CI: 0.66-1.21)) or six-month culture conversion (aITT relative risk: 0.94 (95% CI: 0.84, 1.02), aPP relative risk: 0.93 (95% CI: 0.83, 1.04)). In regimens containing combinations of three likely effective, highly active anti-TB drugs the addition of delamanid had no discernible effect on culture conversion at two or six months. As the standard of care for MDR/RR-TB treatment becomes more potent, it may become increasingly difficult to detect the benefit of adding a single agent to standard of care MDR/RR-TB regimens. Novel approaches like those implemented may help account for background regimens and establish effectiveness of new chemical entities.

TZAP overexpression induces telomere dysfunction and ALT-like activity in ATRX/DAXX-deficient cells.

The appropriate regulation of telomere length homeostasis is crucial for the maintenance of genome integrity. The telomere-binding protein TZAP has been suggested to regulate telomere length by promoting t-circle and c-circle excisions through telomere trimming, yet the molecular mechanisms by which TZAP functions at telomeres are not understood. Using a system based on TZAP overexpression, we show that efficient TZAP recruitment to telomeres occurs in the context of open telomeric chromatin caused by loss of ATRX/DAXX independently of H3.3 deposition. Moreover, our data indicate that TZAP binding to telomeres induces telomere dysfunction and ALT-like activity, resulting in the generation of t-circles and c-circles in a Bloom-Topoisomerase IIIα-RMI1-RMI2 (BTR)-dependent manner.

Hyperextended telomeres promote formation of C-circle DNA in telomerase positive human cells.

Telomere length maintenance is crucial to cancer cell immortality. Up to 15% of cancers utilize a telomerase-independent, recombination-based mechanism termed alternative lengthening of telomeres (ALT). Currently, the primary ALT biomarker is the C-circle, a type of circular DNA with extrachromosomal telomere repeats (cECTRs). How C-circles form is not well characterized. We investigated C-circle formation in the human cen3tel cell line, a long-telomere, telomerase+ (LTT+) cell line with progressively hyper-elongated telomeres (up to ∼100 kb). cECTR signal was observed in 2D gels and C-circle assays but not t-circle assays, which also detect circular DNA with extrachromosomal telomere repeats. Telomerase activity and C-circle signal were not separable in the analysis of clonal populations, consistent with C-circle production occurring within telomerase+ cells. We observed similar cECTR results in two other LTT+ cell lines, HeLa1.3 (∼23 kb telomeres) and HeLaE1 (∼50 kb telomeres). In LTT+ cells, telomerase activity did not directly impact C-circle signal; instead, C-circle signal correlated with telomere length. LTT+ cell lines were less sensitive to hydroxyurea than ALT+ cell lines, suggesting that ALT status is a stronger contributor to replication stress levels than telomere length. Additionally, the DNA repair-associated protein FANCM did not suppress C-circles in LTT+ cells as it does in ALT+ cells. Thus, C-circle formation may be driven by telomere length, independently of telomerase and replication stress, highlighting limitations of C-circles as a stand-alone ALT biomarker.

Hyperextended telomeres promote C-circle formation in telomerase positive human cells.

Telomere length maintenance is crucial to cancer cell immortality. Up to 15% of cancers utilize a telomerase-independent, recombination-based mechanism termed alternative lengthening of telomeres (ALT). The primary ALT biomarker is the C-circle, a type of circular DNA with extrachromosomal telomere repeats (cECTRs). How C-circles form is not well characterized. To investigate C-circle formation in telomerase+ cells, we studied the human cen3tel cell line, in which telomeres progressively hyper-elongated post TERT -immortalization. cECTR signal was observed in 2D gels and C-circle assays but not t-circle assays, which also detect cECTRs. Telomerase activity and C-circle signal were not separable in the analysis of clonal populations, consistent with C-circle production occurring within telomerase+ cells. Two other long telomere, telomerase+ (LTT+) cell lines, HeLa1.3 (~23 kb telomeres) and HeLaE1 (~50 kb telomeres), had similar cECTR properties. Telomerase activity did not directly impact C-circle signal in LTT+ cells; instead, C-circle signal correlated with telomere length. LTT+ lines were less sensitive to hydroxyurea than an ALT+ cell line, suggesting that ALT status is a stronger contributor to replication stress levels than telomere length. Additionally, FANCM did not suppress C-circles in LTT+ cells as it does in ALT+ cells. Thus, C-circle formation may be driven by telomere length, independently of telomerase and replication stress, highlighting limitations of C-circles as a stand-alone ALT biomarker.

Intraoperative sentinel node biopsy, is it worth the wait?

INTRODUCTION: In our institution, the study of selective sentinel node biopsy (SLNB) is performed intraoperatively. The main objective of our study is to know the proportion of patients who benefits from the waiting of the results of SLNB. METHODS: A retrospective analysis of patients operated on our center between January 1st, 2018 and June 30, 2019 was carried out. We included women diagnosed with T1-T2 tumors, treated by lumpectomy and SLNB studied using OSNA method. RESULTS: Our study included 149 women. There were not statistically significant differences in terms of demographic data between the group treated with axillary lymph node dissection (ALND) and exclusively SLNB group. After analysis of SLN intraoperatively, there were performed 18 axillary lymphadenectomies. Only in six of this 18 cases, three or more sentinel nodes were founded. The location of the tumor, the presence of lymphovascular permeation and the total tumor load (TTL) showed statistically significant differences between groups. Only the TTL was established as the independent factor of the need for ALND. DISCUSSION: Obtaining a deferred result of the SLNB allowed reducing the time of anesthesia and occupation of the operating room, since in a high percentage of cases an additional procedure is not performed.

Cancer and Non-cancer Fatigue Treated With Bupropion: A Systematic Review.

CONTEXT: Fatigue is a predominant and distressing symptom in cancer and non-cancer conditions for which there is a paucity of recommendations for pharmacological interventions. Bupropion is a novel treatment whose efficacy and safety in the treatment of fatigue are unknown. OBJECTIVES: This study aimed to systematically assess the evidence on the efficacy and safety of bupropion in the treatment of fatigue in people with cancer and non-cancer conditions. METHODS: PubMed, EMBASE, and Ovid Medline databases were searched up to July 26, 2022. Studies were included if they reported bupropion as an intervention for cancer and non-cancer-related fatigue and used an objective scale to assess symptom outcomes. Experimental and quasi-experimental studies in adult patients published in English were included. RESULTS: This review reports on seven studies (three randomized studies, three non-randomized studies, and one case series) that enrolled a total of 584 patients. Bupropion was tested in five studies for treating cancer-related fatigue and in two studies for treating fatigue in non-cancer conditions. The reviewed studies were heterogeneous in relation to the scales used to assess fatigue. Six out of seven studies reported that bupropion significantly reduced the fatigue burden without causing major adverse effects. These positive results must be taken with caution caused by the small sample sizes and low quality of the studies reviewed. CONCLUSION: Bupropion may prove to be an effective and safe intervention for fatigue in cancer and non-cancer conditions. A high-quality randomized trial is warranted to test current preliminary results.

Quantification of Cannabis in Infused Consumer Products and Their Residues on Skin.

Cannabis consumer products are a $4.6 billion industry in the U.S. that is projected to exceed $14 billion by 2025. Despite an absence of U.S. Food and Drug Administration (FDA) regulation or clinical data, thousands of nutraceuticals, topical consumer products, and beauty products claim benefits of hemp or cannabidiol. However, a lack of required quality control measures prevents consumers from knowing the true concentration or purities of cannabis-labeled products. Thirteen over-the-counter consumer products were examined for the presence of cannabidiol (CBD), cannabinol (CBN), Δ9-tetrahydrocannabinol (THC), cannabidiolic acid (CBDA), and Δ9-tetrahydrocannabinolic acid A (THCA). Additionally, the efficacy of topical applications was investigated using a porcine skin model, in which particle size and zeta potential relate to skin permeability. Skin permeation was correlated to particle size and relative stability in skin-like conditions but not directly related to the CBD content, suggesting that topical products can be designed to enhance overall skin permeation. Of the products analyzed, all products have some traceable amount of cannabinoids, while seven products had multiple cannabinoids with quantifiable amounts. Overall, the need for further regulation is clear, as most products have apparent distinctions between their true and labeled contents.

CD9 expression in porcine blood CD4+ T cells delineates two subsets with phenotypic characteristics of central and effector memory cells.

In this report, we describe the characterization of a new monoclonal antibody, named 4H5CR4, against porcine CD9. Its use in combination with antibodies to CD4, CD8α, and 2E3 allows to distinguish at least five main CD4+ T cell subsets. Analysis on these subsets of CD45RA, CD27, CD29, CD95, CCR7, and SLA-DR markers depicts a progressive model of CD4+ T cell development. CD4+ 2E3+ CD8α- CD9- cells are the least differentiated population of naïve cells, whereas the CD4+ 2E3- CD8α+CD9+ and CD4+ 2E3- CD8α+ CD9- cells display phenotypic features of central and effector memory T helper cells, respectively. The latter subsets were able to produce IFN-γ after polyclonal activation with PMA/Ionomycin; however, in vitro virus-specific IFN-γ production of PBMCs collected at 38-44 days after pseudorabies virus vaccination was dominated by cells with a CD9+ phenotype. Therefore, CD9 appears to be a useful marker to investigate CD4+ T cell heterogeneity in swine.