A pathogen branched-chain amino acid catabolic pathway subverts host survival by impairing energy metabolism and the mitochondrial UPR.

The mitochondrial unfolded protein response (UPRmt) is a stress-activated pathway promoting mitochondrial recovery and defense against infection. In C. elegans, the UPRmt is activated during infection with the pathogen Pseudomonas aeruginosa-but only transiently. As this may reflect a pathogenic strategy to target a pathway required for host survival, we conducted a P. aeruginosa genetic screen to uncover mechanisms associated with this temporary activation. Here, we find that loss of the P. aeruginosa acyl-CoA dehydrogenase FadE2 prolongs UPRmt activity and extends host survival. FadE2 shows substrate preferences for the coenzyme A intermediates produced during the breakdown of the branched-chain amino acids valine and leucine. Our data suggests that during infection, FadE2 restricts the supply of these catabolites to the host hindering host energy metabolism in addition to the UPRmt. Thus, a metabolic pathway in P. aeruginosa contributes to pathogenesis during infection through manipulation of host energy status and mitochondrial stress signaling potential.

Recommendations related to occupational infection prevention and control training to protect healthcare workers from infectious diseases: a scoping review of infection prevention and control guidelines.

BACKGROUND: Events such as the COVID-19 pandemic remind us of the heightened risk that healthcare workers (HCWs) have from acquiring infectious diseases at work. Reducing the risk requires a multimodal approach, ensuring that staff have the opportunity to undertake occupational infection prevention and control (OIPC) training. While studies have been done within countries to look at availability and delivery of OIPC training opportunities for HCWs, there has been less focus given to whether their infection prevention and control (IPC) guidelines adhere to recommended best practices. OBJECTIVES: To examine national IPC guidelines for the inclusion of key recommendations on OIPC training for HCWs to protect them from infectious diseases at work and to report on areas of inconsistencies and gaps. METHODS: We applied a scoping review method and reviewed guidelines published in the last twenty years (2000-2020) including the IPC guidelines of World Health Organization and the United States Centers for Disease Control and Prevention. These two guidelines were used as a baseline to compare the inclusion of key elements related to OIPC training with IPC guidelines of four high-income countries /regions i.e., Gulf Cooperation Council, Australia, Canada, United Kingdom and four low-, and middle-income countries (LMIC) i.e. India, Indonesia, Pakistan and, Philippines. RESULTS: Except for the Filipino IPC guideline, all the other guidelines were developed in the last five years. Only two guidelines discussed the need for delivery of OIPC training at undergraduate and/or post graduate level and at workplace induction. Only two acknowledged that training should be based on adult learning principles. None of the LMIC guidelines included recommendations about evaluating training programs. Lastly the mode of delivery and curriculum differed across the guidelines. CONCLUSIONS: Developing a culture of learning in healthcare organizations by incorporating and evaluating OIPC training at different stages of HCWs career path, along with incorporating adult learning principles into national IPC guidelines may help standardize guidance for the development of OIPC training programs. Sustainability of this discourse could be achieved by first updating the national IPC guidelines. Further work is needed to ensure that all relevant healthcare organisations are delivering a package of OIPC training that includes the identified best practice elements.

Dual energy CT angiography for lower extremity trauma: comparison with conventional CT.

PURPOSE: To determine if rapid switching dual-energy CT (rsDECT) provides improvements in vascular attenuation, subjective diagnostic quality, and detection of vascular injuries compared to conventional CT in trauma patients undergoing lower extremity CT angiography. MATERIALS AND METHODS: The IRB approved this HIPAA-compliant retrospective study. Informed consent was waived. Thirty-nine patients with acute lower extremity trauma including gunshot wounds (19 patients), falls (6 patients), motor vehicle accidents (5 patients), stab wounds (4 patients), pedestrian struck (2 patients), and unspecified trauma (3 patients) who underwent IV contrast-enhanced rsDECT angiography of the lower extremities on a rapid-kilovoltage-switching dual-energy CT scanner (Revolution CT, GE Healthcare) from 6/4/2019 to 1/14/2021 were studied. 7 patients were initially positive for vascular injury on conventional CT, while 32 patients were negative. Blended CT reconstructions simulating conventional 120 kVp single-energy CT, and rsDECT reconstructions (50 keV monoenergetic and iodine density maps) were reviewed. Region of interest contrast density measurements were recorded on conventional and 50 keV reconstructions at multiple levels from the distal aorta to the ankles and compared using Wilcoxon signed-rank tests. Vascular contrast density of 150 HU was used as a minimum cutoff for diagnostically adequate opacification. Images were interpreted by consensus for subjective image quality and presence of injury on both conventional and DECT reconstructions by two fellowship-trained abdominal radiologists blinded to clinical data, and compared using the paired McNemar test. RESULTS: Density measurement differences between conventional and rsDECT at every level of the bilateral lower extremities were statistically significant, with the average difference ranging from 304 Hounsfield units (HU) in the distal aorta to 121 HU at the ankles (p < 0.0001). Using a cutoff of 150 HU, 9.5% (93/976) and 3.1% of vascular segments (30/976) were considered non-diagnostic in the conventional and rsDECT groups, respectively, a reduction of 67.7% (p < 0.0001). Subjective image quality between conventional and rsDECT was not statistically significant, but there were 7 vascular segments out of a total of 976 segments across 3 different patients out of a total of 39 patients in which diagnostic quality was upgraded from non-diagnostic on conventional CT to diagnostic on rsDECT, all of which showed suboptimal bolus quality on conventional CT (unmeasurable in 4/7 and ranging from 56-146 HU in the remaining 3). Similarly, rate of injury detection was identical between conventional CT (15/39 patients) and DECT (15/39 patients). CONCLUSIONS: Vascular contrast density is statistically significantly higher with rsDECT compared to conventional CT, and subjective image quality was upgraded from non-diagnostic on conventional CT to diagnostic on rsDECT in 7 vascular segments across 3 patients. CLINICAL RELEVANCE: rsDECT provides greater vascular contrast density than conventional CT, with potential to salvage suboptimal examinations caused by poor contrast opacification.

Proximal Biotinylation-Based Combinatory Approach for Isolating Integral Plasma Membrane Proteins.

Comprehensive profiling of the cell-surface proteome has been challenging due to the lack of tools for an effective and reproducible way to isolate plasma membrane proteins from mammalian cells. Here we employ a proximity-dependent biotinylation approach to label and isolate plasma membrane proteins without an extra in vitro labeling step, which we call Plasma Membrane-BioID. The lipid-modified BirA* enzyme (MyrPalm BirA*) was targeted to the inner leaflet of the plasma membrane, where it effectively biotinylated plasma membrane proteins. Biotinylated proteins were then affinity-purified and analyzed by mass spectrometry. Our analysis demonstrates that combining conventional sucrose density gradient centrifugation and Plasma Membrane-BioID is ideal to overcome the inherent limitations of the identification of integral membrane proteins, and it yields highly pure plasma components for downstream proteomic analysis.

Improving the impact of non-pharmaceutical interventions during COVID-19: examining the factors that influence engagement and the impact on individuals.

BACKGROUND: During an evolving outbreak or pandemic, non-pharmaceutical interventions (NPIs) including physical distancing, isolation, and mask use may flatten the peak in communities. However, these strategies rely on community understanding and motivation to engage to ensure appropriate compliance and impact. To support current activities for COVID-19, the objectives of this narrative review was to identify the key determinants impacting on engagement. METHODS: An integrative narrative literature review focused on NPIs. We aimed to identify published peer-reviewed articles that focused on the general community (excluding healthcare workers), NPIs (including school closure, quarantine, isolation, physical distancing and hygiene behaviours), and factors/characteristics (including social, physical, psychological, capacity, motivation, economic and demographic) that impact on engagement. RESULTS: The results revealed that there are a range of demographic, social and psychological factors underpinning engagement with quarantine, school closures, and personal protective behaviours. Aside from the factors impacting on acceptance and compliance, there are several key community concerns about their use that need to be addressed including the potential for economic consequences. CONCLUSION: It is important that we acknowledge that these strategies will have an impact on an individual and the community. By understanding the barriers, we can identify what strategies need to be adopted to motivate individuals and improve community compliance. Using a behavioural framework to plan interventions based on these key barriers, will also ensure countries implement appropriate and targeted responses.

Identification and Characterization of the Caspase-Mediated Apoptotic Activity of Teucrium mascatense and an Isolated Compound in Human Cancer Cells.

Plants of the genus Teucrium (Lamiaceae or Labiatae family) are known historically for their medicinal value. Here, we identify and characterize the anticancer potential of T. mascatense and its active compound, IM60, in human cancer cells. The anti-proliferative effect of a T. mascatense methanol extract and its various fractions were analyzed in MCF-7 and HeLa cells in a dose- and time dependent manner. The dichloromethane fraction (TMDF) was observed to be the most effective with cytotoxicity against a more expanded series of cell lines, including MDA-MB-231. A time and dose-dependent toxicity profile was also observed for IM60; it could induce rapid cell death (within 3 h) in MCF-7 cells. Activation of caspases and PARP, hallmarks of apoptotic cell death pathways, following treatment with TMDF was demonstrated using western blot analysis. Inversion of the phosphatidylserine phospholipid from the inner to the outer membrane was confirmed by annexin V staining that was inhibited by the classical apoptosis inhibitor, Z-VAK-FMK. Changes in cell rounding, shrinkage, and detachment from other cells following treatment with TMDF and IM60 also supported these findings. Finally, the potential of TMDF and IM60 to induce enzymatic activity of caspases was also demonstrated in MCF-7 cells. This study, thus, not only characterizes the anticancer potential of T. mascatense, but also identifies a lead terpenoid, IM60, with the potential to activate anticancer cell death pathways in human cancer cells.

Differential Cytotoxic Potential of Acridocarpus orientalis Leaf and Stem Extracts with the Ability to Induce Multiple Cell Death Pathways.

This study systematically analyzed the anticancer potential of Acridocarpus orientalis (AO), a traditional medicinal plant of the Arabian Peninsula/East Africa known for its anti-inflammatory and pain relief properties. Tests of serial organic fractions from methanolic extracts of its leaves and stems revealed that only some fractions showed anti-proliferative potential with the dichloromethane fraction from leaves (AOD (L)) showing the most cytotoxic effect against both breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cell lines. The n-butanol fraction from the stems (AOB (S)), on the other hand, was more effective against cervical cancer cells and did not harm the normal cells. Further characterization of the mode of cell killing revealed that AOD (L) depended more on non-apoptotic pathways for its cytotoxicity in breast cancer cells, while it could activate some apoptosis and necroptosis in HeLa cells. The AOB (S) fraction could primarily activate apoptosis and some necroptosis in HeLa cells. Both fractions perturbed autophagy, but in a dissimilar manner. Thus, different parts of A. orientalis revealed variable potential to induce cell death in cancer cells via apoptotic and non-apoptotic pathways, making A. orientalis a valuable plant for the exploration of anticancer bioactive reagents, some of which may be protective for normal cells.

The mitochondrial unfolded protein response: Signaling from the powerhouse.

Mitochondria are multifaceted and indispensable organelles required for cell performance. Accordingly, dysfunction to mitochondria can result in cellular decline and possibly the onset of disease. Cells use a variety of means to recover mitochondria and restore homeostasis, including the activation of retrograde pathways such as the mitochondrial unfolded protein response (UPRmt). In this Minireview, we will discuss how cells adapt to mitochondrial stress through UPRmt regulation. Furthermore, we will explore the current repertoire of biological functions that are associated with this essential stress-response pathway.

Diffusion-weighted imaging of the pericholecystic hepatic parenchyma for distinguishing acute and chronic cholecystitis.

PURPOSE: The purpose of this study is to measure the performance of restricted diffusion of the pericholecystic hepatic parenchyma for distinguishing between acute and chronic cholecystitis. METHODS: The institutional review board approved this HIPAA-compliant retrospective study. Two hundred sixty-six patients presenting with acute right upper quadrant pain between 10/3/2010 and 11/28/2012 undergoing MR within 48 h of equivocal utility of ultrasound (US) were included. Diffusion-weighted imaging (DWI) sequences (b = 0, 600 s/mm2, apparent diffusion coefficient (ADC) maps) were reviewed and graded in a blinded fashion by two abdominal fellowship-trained radiologists for the presence of restricted diffusion in the pericholecystic hepatic parenchyma and the gallbladder wall. Sensitivity, specificity, and inter-observer agreement for individual imaging signs were calculated using surgical pathology as the reference standard for acute cholecystitis. RESULTS: Of the 266 patients, 113 were treated conservatively and 153 underwent cholecystectomy. Restricted diffusion of the pericholecystic hepatic parenchyma showed low sensitivity (reviewer 1, 40%; reviewer 2, 30%) and moderately high specificity (reviewer 1, 84%; reviewer 2, 75%) for distinguishing acute and chronic cholecystitis. Restricted diffusion in the gallbladder wall showed low sensitivity (reviewer 1, 30%; reviewer 2, 7%) and high specificity (reviewer 1, 93%; reviewer 2, 97%) for distinguishing acute and chronic cholecystitis. CONCLUSION: Diffusion-weighted imaging of the pericholecystic hepatic parenchyma shows moderately high specificity for distinguishing between acute and chronic cholecystitis.

A Presentation of Meige Syndrome With Associated Upper Motor Neuron Symptoms.

Meige syndrome (MS) is a cranial dystonia that involves blepharospasm and oromandibular dystonia. It can also evolve to include other adjacent muscle groups in the cervical region. It typically presents in middle-aged females, and while the disorder is relatively uncommon, its exact prevalence varies. Diagnosis is typically made with a thorough history and physical and workup to rule out other causes. Treatment options include medical management with gamma-aminobutyric acid (GABA) antagonists, dopamine antagonists, and anticholinergics for short-term management. Long-term treatment options are Botox and deep brain stimulation. This case report presents a 56-year-old female with a complex presentation of MS; the patient's symptoms progressed from isolated blepharospasms to involve orofacial and cervical musculature. A distinctive aspect of this case was the simultaneous presence of upper motor neuron (UMN) signs in the patient alongside acute to subacute compression fractures of the superior endplate of C7 and T3, as revealed by cervical spine imaging. Treatment with clonazepam led to significant symptomatic improvement, highlighting the importance of a multimodal approach in managing MS. This case underscores the need for careful clinical evaluation, collaboration with movement disorder specialists, and ongoing research efforts to enhance understanding and treatment of MS.

Multifaceted Impact of the Coronavirus Disease 2019 (COVID-19) Pandemic on ST-Elevation Myocardial Infarction (STEMI): A Literature Review of Incidence, Treatment Modalities, and Outcomes.

The global repercussions of coronavirus disease 2019 (COVID-19) include substantial worldwide mortality and have brought to light existing gaps in healthcare systems. Particularly, diseases requiring time-sensitive treatment, such as ST-elevation myocardial infarction (STEMI), have faced significant challenges due to the impact and revelations of the COVID-19 pandemic on healthcare infrastructure. This review addresses the impact of the pandemic on STEMI, exploring incidence, treatment modalities, and clinical outcomes. Through a critical examination of existing literature, the intricate relationship between the pandemic and cardiovascular health, specifically STEMI, is elucidated. The COVID-19 pandemic has had a significant impact on the management of STEMI, with changes in hospitalization rates, treatment strategies, and the presentation of the disease posing significant challenges. The contradictory results of COVID-19 and post-vaccine myocardial infarction, as well as gender differences in reported cases, highlight the need for further research to clarify these relationships.

Effect of acetylcholinesterase inhibition on immune cells in the murine intestinal mucosa.

The gastrointestinal tract (GI) is the largest immune organ whose function is controlled by a complex network of neurons from the enteric nervous system (ENS) as well as the sympathetic and parasympathetic system. Evolving evidence indicates that cross-communication between gut-innervating neurons and immune cells regulates many essential physiological functions including protection against mucosal infections. We previously demonstrated that following paraoxon treatment, 70 % of the mice were able to survive an oral infection with S. typhimurium, a virulent strain of Salmonella enterica serovar Typhimurium. The present study aims to investigate the effect that rivastigmine, a reversible AChE inhibitor used for the treatment of neurodegenerative diseases, has on the murine immune defenses of the intestinal mucosa. Our findings show that, similar to what is observed with paraoxon, administration of rivastigmine promoted the release of secretory granules from goblet and Paneth cells, resulting in increased mucin layer. Surprisingly, however, and unlike paraoxon, rivastigmine treatment did not affect overall mortality of infected mice. In order to investigate the mechanistic basis for the differential effects observed between paraoxon and rivastigmine, we used multi-color flowcytometric analysis to characterize the immune cell landscape in the intraepithelial (IE) and lamina propria (LP) compartments of intestinal mucosa. Our data indicate that treatment with paraoxon, but not rivastigmine, led to an increase of resident CD3+CD8+ T lymphocytes in the ileal mucosa (epithelium and lamina propria) and CD11b- CD11c+ dendritic cells in the LP. Our findings indicate the requirement for persistent cholinergic pathway engagement to effect a change in the cellular landscape of the mucosal tissue that is necessary for protection against lethal bacterial infections. Moreover, optimal protection requires a collaboration between innate and adaptive mucosal immune responses in the intestine.

Biocompatibility of calcined mesoporous silica particles with ventricular myocyte structure and function.

In vivo and in vitro systems were employed to investigate the biocompatibility of two forms of calcined mesoporous silica microparticles, MCM41-cal and SBA15-cal, with ventricular myocytes. These particles have potential clinical use in delivering bioactive compounds to the heart. Ventricular myocytes were isolated from 6 to 8 week male Wistar rats. The distribution of the particles in ventricular myocytes was investigated by transmission electron microscopy and scanning electron microscopy. The distribution of particles was also examined in cardiac muscle 10 min after intravenous injection of 2.0 mg/mL MCM41-cal. Myocyte shortening and the Ca(2+) transient were determined following exposure to 200 µg/mL MCM41-cal or SBA15-cal for 10 min. Within 10 min of incubation at 25 °C, both MCM41-cal and SBA15-cal were found attached to the plasma membrane, and some particles were observed inside ventricular myocytes. MCM41-cal was more abundant inside the myocytes than SBA15-cal. The particles had a notable affinity to mitochondrial membranes, where they eventually settled. Within 10 min of intravenous injection (2.0 mg/mL), MCM41-cal traversed the perivascular space, and some particles entered ventricular myocytes and localized around the mitochondrial membranes. The amplitude of shortening was slightly reduced in myocytes superperfused with MCM41-cal or SBA15-cal. The amplitude of the Ca(2+) transient was significantly reduced in myocytes superperfused with MCM41-cal but was only slightly reduced with SBA15-cal. Overall, the results show reasonable bioavailability and biocompatibility of MCM41-cal and SBA15-cal with ventricular myocytes.

Five Things to Know About Incremental Peritoneal Dialysis.

Incremental peritoneal dialysis (PD) offers patients newly starting dialysis less than the standard "full dose" of PD, reducing treatment burden and intrusiveness while minimizing symptoms of renal failure. Incremental PD is a cost-effective approach that has been associated with slower rates of decline in residual kidney function. This approach also produces less waste and in turn reduces environmental footprint compared to standard PD prescriptions. It also aligns with the International Society of Peritoneal Dialysis (ISPD) Practice Recommendations for high-quality, goal-oriented therapy. Awareness of incremental PD along with its advantages and limitations provides practitioners with the tools to provide more patient-centered dialysis prescriptions in appropriate populations.

La dialyse péritonéale (DP) incrémentale propose un traitement à une dose moindre que la « dose complète ¼ habituelle aux patients qui amorcent la dialyse; ce qui contribue à réduire le fardeau du traitement et à en limiter le caractère intrusif, tout en minimisant les symptômes de l'insuffisance rénale. La DP incrémentale est une approche qui présente un bon rapport coût/efficacité, en plus d'avoir été associée à un ralentissement du déclin de la fonction rénale résiduelle. Elle produit également moins de déchets que la DP standard, ce qui, par conséquent, réduit l'empreinte environnementale du traitement. Enfin, la DP incrémentale est conforme aux recommandations de pratique de l'International Society of Peritoneal Dialysis (ISPD) pour une thérapie de haute qualité axée sur les objectifs. La sensibilisation à la DP incrémentale, ainsi qu'à ses avantages et à ses limites, fournit aux praticiens les outils nécessaires pour prescrire une modalité de dialyse davantage centrée sur le patient dans les populations appropriées.

Supporting the Delivery of Infection Prevention and Control Training to Healthcare Workers: Insights from the Sector.

Infection prevention and control (IPC) cannot be implemented without healthcare workers (HCWs) being properly trained and competent. The provision of training is essential, yet there is a gap in our understanding of the factors impacting the implementation of IPC training. This paper reports the results from in-depth interviews that explored the current landscape around IPC training delivered across low-, middle-, and high-income countries. Semi-structured interviews were conducted with the key stakeholders involved in policymaking or IPC implementation in Saudi Arabia, Pakistan, India, Indonesia, the Philippines, and Australia. Although the training was mandated for many HCWs, participants indicated that only some training elements were mandatory. Participants spoke about covering various topics, but those in low-resource settings spoke about the challenges of delivering training. Classroom-based training dominated, but online delivery modes were also used in some locations. Whilst HCW's training was postulated to have improved during the COVID-19 pandemic, the capacity to deliver training did not improve in some settings. More research is needed to establish the essential elements that could underpin the development of training packages.

On the offense and defense: mitochondrial recovery programs amidst targeted pathogenic assault.

Bacterial pathogens employ a variety of tactics to persist in their host and promote infection. Pathogens often target host organelles in order to benefit their survival, either through manipulation or subversion of their function. Mitochondria are regularly targeted by bacterial pathogens owing to their diverse cellular roles, including energy production and regulation of programmed cell death. However, disruption of normal mitochondrial function during infection can be detrimental to cell viability because of their essential nature. In response, cells use multiple quality control programs to mitigate mitochondrial dysfunction and promote recovery. In this review, we will provide an overview of mitochondrial recovery programs including mitochondrial dynamics, the mitochondrial unfolded protein response (UPRmt ), and mitophagy. We will then discuss the various approaches used by bacterial pathogens to target mitochondria, which result in mitochondrial dysfunction. Lastly, we will discuss how cells leverage mitochondrial recovery programs beyond their role in organelle repair, to promote host defense against pathogen infection.

A Case of Transient Global Amnesia: A Rare Diagnosis.

Transient global amnesia (TGA) is a syndrome characterized by a loss of anterograde memory with a less prominent loss in retrograde episodic memory that resolves within 24 hours or less. In this report, we present a rare case of a 62-year-old male who presented to the emergency department with sudden onset confusion and memory loss. Prior to this, the patient had no significant medical or psychiatric history. Magnetic resonance imaging (MRI) and computerized tomography (CT) showed a normal presentation, and a neurology consultation ruled out any organic brain abnormalities. After ruling out all other potential causes, diagnosis of transient global amnesia was made. We present this case highlighting the importance of ruling out other acutely morbid conditions when addressing TGA, guidance on timing of imaging, as well as offering insight on other etiologies of this condition.

Intestinal permeability studies of sulpiride incorporated into self-microemulsifying drug delivery system (SMEDDS).

The objective of the present study was to determine the intestinal absorption of sulpiride incorporated into SMEDDS by means of single-pass intestinal perfusion method (SPIP) in rat and to compare the effective permeability coefficient obtained with that of drug solution and micellar solution. The prepared SMEDDS and micelles formulations were investigated for droplets size. SPIP experiment was performed using the three formulations in three of the secluded regions of the small intestine (duodenum, jejunum, and ileum). The amount of the drug in the samples was estimated by HPLC and the effective permeability coefficients in rats were calculated. The human intestinal permeability was predicted based on rat effective permeability coefficient value. The dilution stability of the formulations was also determined. The average droplet size of SMEDDS and micelles was 9.27 nm and 7.20 nm respectively. The effective permeability coefficient of sulpiride was appreciably lower in the ileum weighed against jejunum and duodenum when administered as a solution (P<0.05). The estimated human absorption of sulpiride for the SMEDDS dilutions was superior to that from solution (P<0.05) and similar to micellar solution. The micellar dilutions were unstable whereas the SMEDDS dilutions were stable. Based on the above results, SMEDDS can be a potential candidate for improving the peroral absorption of the sulpiride.

Prevalence and Sociodemographic Covariates of Cervical Cancer and Its Association With Menstrual Irregularities: Findings From the 2017 National Inpatient Sample Database.

Background and objective Menstrual irregularities and sociodemographic factors such as increasing age, Hispanic race, low socioeconomic strata, and low income status are known risk factors for cervical cancer. This study aimed to examine the prevalence of cervical cancer and its association with menstrual irregularities and other known risk factors based on a large nationwide inpatient sample database. Methods We used the Nationwide Inpatient Sample (NIS) database for the year 2017 and identified cases where cervical cancer and menstrual irregularities are the primary and co-occurring diagnoses using the International Classification of Diseases, Tenth Revision (ICD-10) codes. Pearson's chi-square test, independent-sample t-test, and multiple logistic regression were used to generate the analysis. Results A total of 15,800 (0.19%) female weighted admissions between the age group of 18-55 years reported a diagnosis of cervical cancer. Patients with a diagnosis of menstrual irregularity had a statistically significant higher odds of association [odds ratio (OR): 1.582] for being diagnosed with cervical cancer. The odds of association were also high for the Hispanic race [OR: 1.280, 95% confidence interval (CI): 1.128-1.453]. The odds of a diagnosis of cervical cancer increased with age, with the highest odds being reported for the age group of 46-55 years (95% CI: 12.107-21.171) and the population with lower median household income, with the highest odds being observed for the lowest interquartile range (95% CI: 1.418-1.892). Conclusion Based on our findings, a diagnosis of menstrual irregularity, the Hispanic race, increasing age, and lower household income are factors that significantly increased the odds of being diagnosed with cervical cancer.

A nematode-derived, mitochondrial stress signaling-regulated peptide exhibits broad antibacterial activity.

A dramatic rise of infections with antibiotic-resistant bacterial pathogens continues to challenge the healthcare field due to the lack of effective treatment regimes. As such, there is an urgent need to develop new antimicrobial agents that can combat these multidrug-resistant superbugs. Mitochondria are central regulators of metabolism and other cellular functions, including the regulation of innate immunity pathways involved in the defense against infection. The mitochondrial unfolded protein response (UPRmt) is a stress-activated pathway that mitigates mitochondrial dysfunction through the regulation of genes that promote recovery of the organelle. In the model organism Caenorhabditis elegans, the UPRmt also mediates an antibacterial defense program that combats pathogen infection, which promotes host survival. We sought to identify and characterize antimicrobial effectors that are regulated during the UPRmt. From our search, we discovered that the antimicrobial peptide CNC-4 is upregulated during this stress response. CNC-4 belongs to the caenacin family of antimicrobial peptides, which are predominantly found in nematodes and are known to have anti-fungal properties. Here, we find that CNC-4 also possesses potent antimicrobial activity against a spectrum of bacterial species and report on its characterization.