Medical Diagnostic Laboratories (United States)

Podcasts serve as an easy, affordable, and on-the-go experience for listeners of all types, particularly those casually broaching a new subject they are interested in learning more about. Podcasting as a tool for pathology education has had a growing reach for several years, and has gained traction as an academic work product for medical education, promoting journals and articles, and attracting trainees to pathology. Yet, there is sparse academic literature reviewing the topic. In this article, we aim to provide a qualitative synthesis of peer-reviewed and other online sources, with objectives including introducing podcasting, reviewing its role in medical education, and exploring issues unique to pathology. National podcasting trends, advantages, and limitations of podcasts in pathology will be covered. Additionally, a comprehensive list of pathology podcasts, quantitative analysis of select podcast downloads, and practical steps for pathologists interested in creating their own podcasts will also be provided.

ABSTRACTRationalePhysicians sometimes encounter various types of gut feelings (GFs) during clinical diagnosis. The type of GF addressed in this paper refers to the intuitive sense that the generated hypothesis might be incorrect. An appropriate diagnosis cannot be obtained unless these GFs are articulated and inventive solutions are devised. Thus, the method of articulating GFs is critical.Aims and ObjectivesThe current study proposes reflective verbalization (RV) to help healthcare professionals capitalize on their GF. In cognitive psychology, RV is the process of verbalizing one's thoughts and feelings through metacognition, to promote deeper understanding and insight problem‐solving. When applied to clinical reasoning, RV can help doctors verbalize their GFs, refining their diagnostic hypotheses.MethodTo address GFs systematically using RV, we introduce the DATES approach, comprising five perspectives: Degree, Abandoned, Time course, Excess, and Shortage. Each perspective prompts physicians to compare their patient's information against typical illness scripts, ensuring no detail is omitted or overlooked.Results and ConclusionThe tool also aids physicians in considering possible differential diagnoses for one or more of these elements. This guiding tool may aid physicians in overcoming biases, including confirmation and anchoring biases, thus improving diagnostic accuracy. This tool is useful for healthcare professionals who wish to improve their clinical reasoning and decision‐making abilities, particularly when they encounter inexplicable contradictions in their diagnostic hypotheses.

Globally, breast cancer is the second leading cause ofcancer-relatedmortality among women. Early detection, accurate diagnosis, and timelytreatment are critical for improving survival rates. Therefore, developinga rapid and highly sensitive diagnostic method for early-stage breastcancer detection is essential. Human epidermal growth factor receptor2 (HER2) is a well-characterized indicator of aggressiveness and poorprognosis in various cancers, including breast cancer. HER2-positivebreast cancer represents about 15–20% of all cases, highlightingthe significance of HER2 as both a prognostic and predictive biomarker.Gold nanoparticles (AuNPs) have emerged as promising tools in cancerdiagnostics due to their unique optical and physicochemical properties.Among these, green-synthesized AuNPs are particularly attractive forbiomedical applications due to their eco-friendliness and biocompatibility. Andrographis paniculata is a medicinal herb traditionallyemployed in the treatment of several diseases. Its leaf extract (ALE)contains various bioactive compounds, including flavonoids and diterpenoids,known for their strong reducing capabilities suitable for AuNP synthesis.In this study, we synthesized AuNPs using ALE (ALE-AuNPs) througha green, one-pot method. The ALE-AuNPs ranged from 11.12 ± 2.10to 43.53 ± 10.53 nm in size, with a zeta potential of −21.00± 0.89 to −44.60 ± 2.36 mV. Cytotoxicity testingon MCF-7 cells indicated good biocompatibility. For targeted detection,the ALE-AuNPs were further functionalized with polyethylene glycol(PEG) and anti-HER2 antibodies, forming ALE-AuNPs+PEG+anti HER2. Thisnanoconjugate successfully detected HER2-positive MCF-7 cells viaa 3,3′,5,5′-tetramethylbenzidine-based colorimetricassay. To the best of our knowledge, this is the first report of asimple green synthesis of AuNPs from ALE for use as a colorimetricprobe in HER2-positive breast cancer detection.

Abstract Vimentin is a type III intermediate filament (IF) protein, that is induced in a large number of solid tumours. A single cysteine at position 328 in vimentin plays a crucial role in assembly, organisation and stability of IFs. However, its exact function during epithelial mesenchymal transition (EMT) and cancer progression has not been investigated. To investigate this, we have transduced wildtype (WT) and C328S vimentin separately in MCF-7 cells that lack endogenous vimentin. The expression of C328-VIM impacted vimentin-actin interactions and induced EMT-like features that include enhanced cell proliferation, migration, invasion accompanied by reduced cell adhesion when compared to the wildtype cells. Functional transcriptomic studies confirmed the upregulation of EMT and mesenchymal markers, downregulation of epithelial markers as well as acquisition of signatures associated with cancer stemness (CD56, Oct4, PROCR and CD49f) thus transforming MCF-7 cells from oestrogen positive to triple reduced (ESR1, PGR, and HER2) status. We also observed a stark increase in the expression of long non-coding RNA,XISTin MCF-7 cells expressing C328-VIM. Targeting the mutant vimentin orXISTby RNA interference partially reversed the phenotypes in C328-VIM expressing MCF-7 cells. Furthermore, introduction of C328-VIM cells into nude mice promoted tumour growth by increasing cancer stemness in an oestrogen independent manner. Altogether, our studies provide insight into how cysteine 328 in vimentin dictates mechano-transduction signals to remodel actin cytoskeleton and protect against EMT and cancer growth via modulating lncRNAXIST. Therefore, targeting vimentin and/orXISTvia RNA interference should be a promising therapeutic strategy for breast cancer treatment.Abstract Figure

Molecular mechanisms of resistance to "last resort" antimicrobials in Enterobacterales The use and misuse of antibiotics in veterinary and human medicine, agriculture, and aquaculture are selecting resistance genes in different bacterial species (Osei Sekyere, 2016; Tang et al., 2017) Owing to this selection pressure, bacterial strains with resistance to several, if not all antibiotics in current use (also known as pandrug resistance), are emerging (Manageiro et al., 2012; Guducuoglu et al., 2018; Kopotsa et al., 2020; Osei Sekyere and Reta, 2020) . Further, more and more of these resistance genes are escaping the chromosome unto mobile genetic elements (MGEs) i.e., plasmids, transposons, integrons, and integrative conjugative elements, under antibiotic pressure, enabling erstwhile susceptible strains to horizontally obtain these mobile resistance genes (Pedersen et al., 2018; Kopotsa et al., 2019 Kopotsa et al., , 2020)) . This worrying trend presents a great challenge for human medicine as recommended antibiotics become ineffective against common bacterial pathogens ( Manageiro et al., 2012; Guducuoglu et al., 2018) . The emergence of carbapenem, colistin, and tigecycline resistance is a perfect example of this phenomenon of antibiotic resistance evolution (Osei Sekyere et al., 2016) . Specifically, the use of extended-spectrum penicillins and cephalosporins to treat penicillin-resistant infections, mediated by AmpCs, bla OXA , bla SHV and bla TEM , led to the selection and evolution of bla CTX-M and plasmid-mediated AmpCs, bla SHV and bla TEM (Bush, 2018) . With the proliferation of the penicillinases and cephalosporinases, particularly through IncF plasmids and other MGEs, carbapenems were introduced to treat infections that were insensitive to the penicillins and cephalosporins, leading to the evolution/emergence and rapid dissemination of the carbapenemases: bla KPC , bla GES ,

Infections with the highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b virus have resulted in the death of millions of domestic birds and thousands of wild birds in the U.S. since January, 2022. Throughout this outbreak, spillovers of the virus to mammals have been frequently documented. Here, we report the detection of HPAI H5N1 virus in dairy cattle herds across several states in the U.S. The affected cows displayed clinical signs encompassing decreased feed intake, altered fecal consistency, respiratory distress, and decreased milk production with abnormal milk. Infectious virus and RNA were consistently detected in milk collected from affected cows. Viral staining in tissues revealed a distinct tropism of the virus for the epithelial cells lining the alveoli of the mammary gland in cows. Analysis of whole genome sequences obtained from dairy cows, birds, domestic cats, and a racoon from affected farms indicated multidirectional interspecies transmissions. Epidemiologic and genomic data revealed efficient cow-to-cow transmission after healthy cows from an affected farm were transported to a premise in a different state. These results demonstrate the transmission of HPAI H5N1 clade 2.3.4.4b virus at a non-traditional interface and to a new and highly relevant livestock species, underscoring the ability of the virus to cross species barriers.

Patient‐related factors are of prognostic importance in acute myeloid leukemia (AML). Likewise, cardiac disorders may limit the tolerance of intensive therapy. Little is known about the prognostic value of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). We analyzed NT‐proBNP levels at diagnosis in 312 AML patients (median age: 61 years; range 17–89 years) treated with 3 + 7‐based induction‐chemotherapy and consolidation with up to four cycles of intermediate or high‐dose ARA‐C. NT‐proBNP levels were elevated in 199 patients (63.8%), normal (0–125 pg/ml) in 113 (36.2%), and highly elevated (>2000 pg/ml) in 20 patients (6.4%). Median NT‐proBNP levels differed significantly among patients with complete remission (153.3 pg/ml), no remission (225.9 pg/ml), or early death (735.5 pg/ml) (p = .002). In multivariate analysis, NT‐proBNP, age, and the 2009 European LeukemiaNet (ELN‐2009) classification were independent predictors of outcome after induction chemotherapy. Overall survival (OS) differed significantly between patients with normal, moderately elevated, and highly elevated NT‐proBNP (p < .001). These differences were observed in all patients and in patients <60 years but not in those ≥60 years. In multivariate analysis, NT‐proBNP, age, and ELN‐2009 remained independent prognostic variables for OS (p < .01). Together, NT‐proBNP is an independent prognostic factor indicating the risk of induction failure, early death, and reduced OS in patients with AML.

Tumour illness and its resistance against existing anticancer therapies pose a serious health concern globally despite the progressive advancement of therapeutic options. The prevailing treatment of HCC using numerous antitumor agents has inflated long-lived complete remissions, but a percentage of individuals still die due to disease recurrence, indicating a need for further exploration of possible anti-tumour regimes. We aim to boost the effectiveness of the HCC treatment by conducting current investigations evaluating the effect of arsenic trioxide (ATO) with different herbal compounds like quercetin and aloe-emodin against liver tumour via inhibition of telomerase, a pro-cancer enzyme. The anticancer activity of ATO with herbal compounds was investigated in human control liver cell line (Wrl-68) and cancer liver cell line (HepG2) at different time intervals. Viability and cytotoxicity in response to combinatorial drugs were assessed in vitro by trypan blue dye exclusion assay and MTT and WST assay. Apoptosis was analysed by annexin V/PI assay, and the expression of telomerase and apoptosis-regulating proteins was evaluated by immunoblotting and qRT-PCR. Arsenic trioxide in combination with quercetin and aloe-emodin reduced cell viability in cancerous cells compared to normal cells by inducing apoptosis, downregulating telomerase and Bcl-2 (anti-apoptotic protein) and upregulating the expression of Bax (pro-apoptotic protein). ATO exhibited significant anticancer effects due to the synergistic effects of quercetin and aloe-emodin in liver tumour cells. The current study data collectively suggest that a successful inhibition of cancer growth by the combination of ATO and tested herbal medicines against liver tumour growth is via the inhibition of telomerase activity.

CDS, JTQ, LMK, SGS and WAF have disclosed no conflicts of interest. CMW has received speaker honorarium from Grifols and Immucor and consulting honorarium from Quotient, Cerus, and ArchOncology with renumeration to New York Blood Center. GAD and MAK are on the Grifols Speakers Bureau. MD has received speaker honorarium from Grifols. RV receives financial support from bioMérieux, Cerus, Fresenius-Kabi, Hemanext, and Hemastrat. STJ receives speaker honorarium from Grifols and Immucor.