Understanding Visual Disorders through Correlation of Clinical and Radiologic Findings.

Patients presenting with visual disturbances often require a neuroimaging approach. The spectrum of visual disturbances includes three main categories: vision impairment, ocular motility dysfunction, and abnormal pupillary response. Decreased vision is usually due to an eye abnormality. However, it can also be related to other disorders affecting the visual pathway, from the retina to the occipital lobe. Ocular motility dysfunction may follow disorders of the cranial nerves responsible for eye movements (ie, oculomotor, trochlear, and abducens nerves); may be due to any abnormality that directly affects the extraocular muscles, such as tumor or inflammation; or may result from any orbital disease that can alter the anatomy or function of these muscles, leading to diplopia and strabismus. Given that pupillary response depends on the normal function of the sympathetic and parasympathetic pathways, an abnormality affecting these neuronal systems manifests, respectively, as pupillary miosis or mydriasis, with other related symptoms. In some cases, neuroimaging studies must complement the clinical ophthalmologic examination to better assess the anatomic and pathologic conditions that could explain the symptoms. US has a major role in the assessment of diseases of the eye and anterior orbit. CT is usually the first-line imaging modality because of its attainability, especially in trauma settings. MRI offers further information for inflammatory and tumoral cases. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Two-row, three-row or powered circular stapler, which to choose when performing colorectal anastomosis? A systematic review and meta-analysis.

PURPOSE: Three types of circular staplers can be used to perform a colorectal anastomosis: two-row (MCS), three-row (TRCS) and powered (PCS) devices. The objective of this meta-analysis has been to provide the existing evidence on which of these circular staplers would have a lower risk of presenting a leak (AL) and/or anastomotic bleeding (AB). METHODS: An in-depth search was carried out in the electronic bibliographic databases Embase, PubMed and SCOPUS. Observational studies were included, since randomized clinical trials comparing circular staplers were not found. RESULTS: In the case of AL, seven studies met the inclusion criteria in the PCS group and four in the TRCS group. In the case of AB, only four studies could be included in the analysis in the PCS group. The AL OR reported for PCS was 0.402 (95%-confidence interval (95%-CI): 0.266-0.608) and for AB: 0.2 (95% CI: 0.08-0.52). The OR obtained for AL in TRCS was 0.446 (95%-CI: 0.217 to 0.916). Risk difference for AL in PCS was - 0.06 (95% CI: - 0.07 to - 0.04) and in TRCS was - 0.04 (95%-CI: - 0.08 to - 0.01). Subgroup analysis did not report significant differences between groups. On the other hand, the AB OR obtained for PCS was 0.2 (95% CI: 0.08-0.52). In this case, no significant differences were observed in subgroup analysis. CONCLUSION: PCS presented a significantly lower risk of leakage and anastomotic bleeding while TRCS only demonstrated a risk reduction in AL. Risk difference of AL was superior in the PCS than in TRCS.

Outcomes of initially nonoperative management of diverticulitis with abscess formation in immunosuppressed patients. DIPLICAB study COLLABORATIVE group.

AIM: Management of diverticulitis with abscess formation in immunosuppressed patients (IMS) remains unclear. The main objective of the study was to assess short- and long-term outcomes between IMS and immunocompetent patients (IC). The secondary aim was to identify risk factors for emergency surgery. METHODS: A nationwide retrospective cohort study was performed at 29 Spanish referral centres between 2015-2019 including consecutive patients with first episode of diverticulitis classified as modified Hinchey Ib or II. IMS included immunosuppressive therapy, biologic therapy, malignant neoplasm with active chemotherapy and chronic steroid therapy. A multivariate analysis was performed to identify independent risk factors to emergency surgery in IMS. RESULTS: A total of 1395 patients were included; 118 IMS and 1277 IC. There were no significant differences in emergency surgery between IMS and IC (19.5% and 13.5%, p = 0.075) but IMS was associated with higher mortality (15.1% vs. 0.6%, p < 0.001). Similar recurrent episodes were found between IMS and IC (28% vs. 28.2%, p = 0.963). Following multivariate analysis, immunosuppressive treatment, p = 0.002; OR: 3.35 (1.57-7.15), free gas bubbles, p < 0.001; OR: 2.91 (2.01-4.21), Hinchey II, p = 0.002; OR: 1.88 (1.26-2.83), use of morphine, p < 0.001; OR: 3.08 (1.98-4.80), abscess size ≥5 cm, p = 0.001; OR: 1.97 (1.33-2.93) and leucocytosis at third day, p < 0.001; OR: 1.001 (1.001-1.002) were independently associated with emergency surgery in IMS. CONCLUSION: Nonoperative management in IMS has been shown to be safe with similar treatment failure than IC. IMS presented higher mortality in emergency surgery and similar rate of recurrent diverticulitis than IC. Identifying risk factors to emergency surgery may anticipate emergency surgery.

Identifying ribosome heterogeneity using ribosome profiling.

Recent studies have revealed multiple mechanisms that can lead to heterogeneity in ribosomal composition. This heterogeneity can lead to preferential translation of specific panels of mRNAs, and is defined in large part by the ribosomal protein (RP) content, amongst other things. However, it is currently unknown to what extent ribosomal composition is heterogeneous across tissues, which is compounded by a lack of tools available to study it. Here we present dripARF, a method for detecting differential RP incorporation into the ribosome using Ribosome Profiling (Ribo-seq) data. We combine the 'waste' rRNA fragment data generated in Ribo-seq with the known 3D structure of the human ribosome to predict differences in the composition of ribosomes in the material being studied. We have validated this approach using publicly available data, and have revealed a potential role for eS25/RPS25 in development. Our results indicate that ribosome heterogeneity can be detected in Ribo-seq data, providing a new method to study this phenomenon. Furthermore, with dripARF, previously published Ribo-seq data provides a wealth of new information, allowing the identification of RPs of interest in many disease and normal contexts. dripARF is available as part of the ARF R package and can be accessed through https://github.com/fallerlab/ARF.

An Unusual Case of an Intradiploic Arachnoid Cyst of the Orbit.

This study reported a case of an arachnoid cyst of the sphenoid bone causing orbital signs and symptoms in a 58-year-old man with progressive proptosis and nonspecific discomfort in the OS. Orbital MRI showed a 3-cm homogeneous cyst within the left greater wing of the sphenoid bone. To the best of our knowledge, this is the first report of an intradiploic arachnoid cyst in the sphenoid bone with atypical radiological features, causing clinical symptoms, and managed through an eyelid approach, achieving a complete resolution with no complications.

Incidence of anastomotic leakage using powered circular staplers versus manual circular staplers for left colorectal anastomosis: a cost-effectiveness analysis.

BACKGROUND: Colorectal anastomotic leakage causes severe consequences for patients and healthcare system as it will lead to increased consumption of hospital resources and costs. Technological improvements in anastomotic devices could reduce the incidence of leakage and its economic impact. The aim of the present study was to assess if the use of a new powered circular stapler is cost-effective. METHOD: This observational study included patients undergoing left-sided circular stapled colorectal anastomosis between January 2018 and December 2021. Propensity score matching was carried out to create two comparable groups depending on whether the anastomosis was performed using a manual or powered circular device. The rate of anastomotic leakage, its severity, the consumption of hospital resources, and its cost were the main outcome measures. A cost-effectiveness analysis comparing the powered circular stapler versus manual circular staplers was performed. RESULTS: A total of 330 patients were included in the study, 165 in each group. Anastomotic leakage rates were significantly different (p = 0.012): 22 patients (13.3%) in the manual group versus 8 patients (4.8%) in the powered group. The effectiveness of the powered stapler and manual stapler was 98.27% and 93.69%, respectively. The average cost per patient in the powered group was €6238.38, compared with €9700.12 in the manual group. The incremental cost-effectiveness ratio was - €74,915.28 per patient without anastomotic complications. CONCLUSION: The incremental cost of powered circular stapler compared with manual devices was offset by the savings from lowered incidence and cost of management of anastomotic leaks.

Mitochondrial DNA and Electron Transport Chain Protein Levels Are Altered in Peripheral Nerve Tissues from Donors with HIV Sensory Neuropathy: A Pilot Study.

Distal sensory polyneuropathy (DSP) and distal neuropathic pain (DNP) remain significant challenges for older people with HIV (PWH), necessitating enhanced clinical attention. HIV and certain antiretroviral therapies (ARTs) can compromise mitochondrial function and impact mitochondrial DNA (mtDNA) replication, which is linked to DSP in ART-treated PWH. This study investigated mtDNA, mitochondrial fission and fusion proteins, and mitochondrial electron transport chain protein changes in the dorsal root ganglions (DRGs) and sural nerves (SuNs) of 11 autopsied PWH. In antemortem standardized assessments, six had no or one sign of DSP, while five exhibited two or more DSP signs. Digital droplet polymerase chain reaction was used to measure mtDNA quantity and the common deletions in isolated DNA. We found lower mtDNA copy numbers in DSP+ donors. SuNs exhibited a higher proportion of mtDNA common deletion than DRGs in both groups. Mitochondrial electron transport chain (ETC) proteins were altered in the DRGs of DSP+ compared to DSP- donors, particularly Complex I. These findings suggest that reduced mtDNA quantity and increased common deletion abundance may contribute to DSP in PWH, indicating diminished mitochondrial activity in the sensory neurons. Accumulated ETC proteins in the DRG imply impaired mitochondrial transport to the sensory neuron's distal portion. Identifying molecules to safeguard mitochondrial integrity could aid in treating or preventing HIV-associated peripheral neuropathy.

MicroRNA Expression Profiles in Human Samples and Cell Lines Revealed Nine miRNAs Associated with Cisplatin Resistance in High-Grade Serous Ovarian Cancer.

Metastasis and drug resistance are major contributors to cancer-related fatalities worldwide. In ovarian cancer (OC), a staggering 70% develop resistance to the front-line therapy, cisplatin. Despite proposed mechanisms, the molecular events driving cisplatin resistance remain unclear. Dysregulated microRNAs (miRNAs) play a role in OC initiation, progression, and chemoresistance, yet few studies have compared miRNA expression in OC samples and cell lines. This study aimed to identify key miRNAs involved in the cisplatin resistance of high-grade-serous-ovarian-cancer (HGSOC), the most common gynecological malignancy. MiRNA expression profiles were conducted on RNA isolated from formalin-fixed-paraffin-embedded human ovarian tumor samples and HGSOC cell lines. Nine miRNAs were identified in both sample types. Targeting these with oligonucleotide miRNA inhibitors (OMIs) reduced proliferation by more than 50% for miR-203a, miR-96-5p, miR-10a-5p, miR-141-3p, miR-200c-3p, miR-182-5p, miR-183-5p, and miR-1206. OMIs significantly reduced migration for miR-183-5p, miR-203a, miR-296-5p, and miR-1206. Molecular pathway analysis revealed that the nine miRNAs regulate pathways associated with proliferation, invasion, and chemoresistance through PTEN, ZEB1, FOXO1, and SNAI2. High expression of miR-1206, miR-10a-5p, miR-141-3p, and miR-96-5p correlated with poor prognosis in OC patients according to the KM plotter database. These nine miRNAs could be used as targets for therapy and as markers of cisplatin response.

Factors associated with venous thromboembolic disease due to failed thromboprophylaxis.

INTRODUCTION: Available evidence to identify factors independently associated with failed thromboprophylaxis (FT) in medical patients is insufficient. The present study seeks to evaluate in hospitalized patients, which clinical factors are associated with the development of FT. MATERIALS AND METHODS: A case-control study nested to a historical cohort, comparing patients who developed failed thromboprophylaxis (cases) with those who did not (controls). Univariate and multivariate regression analysis was performed to define the factors associated with FT. RESULTS: We selected 204 cases and 408 controls (52.4% men, median age 63 years). Medical patients were 78.4%. The most frequent thromboprophylaxis scheme was enoxaparin. In the failed thromboprophylaxis group, most of the embolic events corresponded to pulmonary embolism (53.4%). Among cases, BMI was higher (26.3 vs. 25 kg/m2, p < 0.001), as was the proportion of patients with leukocytosis > 13,000 (27% vs. 18.9%, p:0.22), and patients who required intensive care management (48% vs. 24.8%, p < 0.001). Factors independently associated with FT were BMI (OR1.04;95%CI 1.00-1.09, p:0.39), active cancer (OR:1.63;95%IC 1.03-2.57, p:0.04), leukocytosis (OR:1.64;95%CI 1.05-2.57, p:0.03) and ICU requirement (OR:3.67;95%CI 2.31-5.83, p < 0.001). CONCLUSION: Our study suggests that the failed thromboprophylaxis is associated with high BMI, active cancer, leukocytosis, and ICU requirement. Future studies should evaluate whether there is benefit in adjusting the thromboprophylaxis scheme in patients with one or more of these factors.

Triclosan-coated barbed sutures in elective laparoscopic colorectal cancer surgery: a propensity score matched cohort study.

BACKGROUND: Most of the studies published to date which assess the role of antibacterial sutures in surgical site infection (SSI) prevention include heterogeneous groups of patients, and it is therefore difficult to draw conclusions. The objective of the present study was to investigate whether the use of Triclosan-coated barbed sutures (TCBS) was associated with a lower incidence of incisional SSI and lower duration of hospital stay compared to standard sutures, in elective laparoscopic colorectal cancer surgery. METHOD: Observational including patients who underwent elective colorectal cancer laparoscopic surgery between January 2015 and December 2020. The patients were divided into two groups according to the suture used for fascial closure of the extraction incision, TCBS vs conventional non-coated sutures (CNCS), and the rate of SSI was analysed. The TCBS cases were matched to CNCS cases by propensity score matching to obtain comparable groups of patients. RESULTS: 488 patients met the inclusion criteria. After adjusting the patients with the propensity score, two new groups of patients were generated: 143 TCBS cases versus 143 CNCS cases. Overall incisional SSI appeared in 16 (5.6%) of the patients with a significant difference between groups depending on the type of suture used, 9.8% in the group of CNCS and 1.4% in the group of TCBS (OR 0.239 (CI 95%: 0.065-0.880)). Hospital stay was significantly shorter in TCBS group than in CNCS, 5 vs 6 days (p < 0.001). CONCLUSION: TCBS was associated with a lower incidence of incisional SSI compared to standard sutures in a cohort of patients undergoing elective laparoscopic colorectal cancer surgery.

Does month of birth influence colorectal cancer prognosis?

PURPOSE: The main aim of this study was to identify a possible association between month of birth of colorectal cancer (CRC) patients and overall survival (OS) or disease-free survival (DFS). METHODS: This observational study included all consecutive adult patients diagnosed with CRC undergoing oncological surgery from January 2005 to December 2019 with a minimum follow-up of 10 years. The outcome variables were locoregional recurrence, death due to cancer progression, OS and DFS. Non-supervised learning techniques (K-means) were conducted to identify groups of months with similar oncologic outcomes. Finally, OS and DFS were analysed using Kaplan-Meier and Cox regression tests. The model was calibrated with resampling techniques and subsequently a cross-validation was performed. RESULTS: A total of 2520 patients were included. Three birth month groups with different oncologic outcomes were obtained. Survival analysis showed between-group differences in OS (p < 0.001) and DFS (p = 0.03). The multivariable Cox proportional hazards model identified the clusters obtained as independent prognostic factors for OS (p < 0.001) and DFS (p = 0.031). CONCLUSION: There is an association between month of birth and oncologic outcomes of CRC. Patients born in the months of January, February, June, July, October and December had better OS and DFS than those born in different months of the year.

The Role of B Cell and T Cell Glycosylation in Systemic Lupus Erythematosus.

Glycosylation is a post-translational modification that affects the stability, structure, antigenicity and charge of proteins. In the immune system, glycosylation is involved in the regulation of ligand-receptor interactions, such as in B-cell and T-cell activating receptors. Alterations in glycosylation have been described in several autoimmune diseases, such as systemic lupus erythematosus (SLE), in which alterations have been found mainly in the glycosylation of B lymphocytes, T lymphocytes and immunoglobulins. In immunoglobulin G of lupus patients, a decrease in galactosylation, sialylation, and nucleotide fucose, as well as an increase in the N-acetylglucosamine bisector, are observed. These changes in glycoisolation affect the interactions of immunoglobulins with Fc receptors and are associated with pericarditis, proteinuria, nephritis, and the presence of antinuclear antibodies. In T cells, alterations have been described in the glycosylation of receptors involved in activation, such as the T cell receptor; these changes affect the affinity with their ligands and modulate the binding to endogenous lectins such as galectins. In T cells from lupus patients, a decrease in galectin 1 binding is observed, which could favor activation and reduce apoptosis. Furthermore, these alterations in glycosylation correlate with disease activity and clinical manifestations, and thus have potential use as biomarkers. In this review, we summarize findings on glycosylation alterations in SLE and how they relate to immune system defects and their clinical manifestations.

An unusual case of proctalgia: kerosene rectal injury.

Kerosene has been described as an uncommon burn injury agent(1). We report a case of a 47-year-old male who presented to the Emergency Department with proctalgia after self-administration of an unknown enema in the context of cocaine intoxication. Physical examination revealed severe perianal inflammation (Figure 1.A) without suppuration and computerized tomography (CT) scan showed free air in mesorectum and retroperitoneum without intraperitoneal free air or fluid (Figure 1.B and 1.C). Rigid rectoscopy demostrated erythematous rectal mucosa without perforation. Subsequently, perineal drainage and debridement were performed. On the fifth postoperative day, the patient reported worsening proctalgia. Examination under anesthesia revealed the presence of new-onsetanal ulcers (Figure 1.D), rigid rectoscopy identified deep ulcers limited to the rectal mucosa and colonoscopy ruled out colon involvement. During reevaluation, the patient disclosed the use of sailboat engine lubrican as the enema, with kerosene being one of its components. These findings were consistent with rectal burn injuries resulting from exposure to kerosene. A laparoscopic end-loop colostomy was performed without any postoperative complications. Follow-up examinations with rigid rectoscopy showed improvement of rectal ulcers (Figure 1.E and 1.F). To our knowledge, this is the first case of rectal burn injuries after kerosene exposure(2,3). Aggressive washout, early colostomy and serial follow-up scopes are key components in the management of these rare injuries.

A diagnostic challenge: chronic cutaneous ulcers as an isolated clinical finding in metastatic Crohn's disease.

Metastasic Crohn disease (MCD) is the most uncommon cutaneous manifestation of Crohn disease. The actual incidence is not clear. There are fewer than 200 cases described in the literature. We report a case of 21 years-old girl that came to our emergency care with large exudative ulcers in the inguinal folds, the vulva, the perianal region and the popliteal fossae. Histopathological examination of the ulcers revealed a non-caseating granulomatous inflammation with abundant multinucleated giant cells and intense lymphocytic infiltrate. Colonoscopy, contrast study of the small bowel and video capsule endoscopy were carried out without evidence of digestive disease. High potency topical steroids (betamethasone 0,5mg/gr twice daily) and 300mg intravenous Infliximab were initiated as the initial line therapy and the ulcers began to heal. We report this case to highlight the presence of cutaneous ulcers without intestinal disease in a young non-pediatric woman as the unique manifestation of the disease.

Sigmoid volvulus: outcomes of treatment and predictors of morbidity and mortality.

PURPOSE: To analyze the treatment outcomes for sigmoid volvulus (SV) and identify risk factors of complications and mortality. METHODS: Observational study of all consecutive adult patients diagnosed with SV who were admitted from January 2000 to December 2020 in a tertiary university institution for conservative management, urgent or elective surgery. Primary outcomes were 30-day postoperative morbidity, mortality and 2-year overall survival (OS), including analysis of risk factors for postoperative morbidity or mortality and prognostic factors for 2-year OS. RESULTS: A total of 92 patients were included. Conservative management was performed in 43 cases (46.7%), 27 patients (29.4%) underwent emergent surgery and 22 (23.9%) were scheduled for elective surgery. Successful decompression was achieved in 87.8% of cases, but the recurrence rate was 47.2%. Mortality rates following episodes were higher for conservative treatment than for urgent or elective surgery (37.2%, 22.2%, 9.1%, respectively; p = 0.044). ASA score > III was an independent risk factor for complications (OR = 5.570, 95% CI = 1.740-17.829, p < 0.001) and mortality (OR = 6.139, 95% CI = 2.629-14.335, p < 0.001) in the 30 days after admission. Patients who underwent elective surgery showed higher 2-year OS than those with conservative treatment (p = 0.011). Elective surgery (HR = 2.604, 95% CI = 1.185-5.714, p = 0.017) and ASA score > III (HR = 0.351, 95% CI = 0.192-0.641, p = 0.001) were independent prognostic factors for 2-year OS. CONCLUSION: Successful endoscopic decompression can be achieved in most SV patients, but with the drawbacks of high recurrence, morbidity and mortality rates. Concurrent severe comorbidities and conservative treatment were independent prognostic factors for morbidity and survival in SV.

Short-term outcomes of colorectal cancer surgery in older patients: a novel nomogram predicting postoperative morbi-mortality.

PURPOSE: To analyze short-term outcomes of curative-intent cancer surgery in all adult patients diagnosed with colorectal cancer undergoing surgery from January 2010 to December 2019 and determine risk factors for postoperative complications and mortality. METHODS: Retrospective study conducted at a single tertiary university institution. Patients were stratified by age into two groups: < 75 years and ≥ 75 years. Primary outcome was the influence of age on 30-day complications and mortality. Independent risk factors for postoperative adverse events or mortality were analyzed, and two novel nomograms were constructed. RESULTS: Of the 1486 patients included, 580 were older (≥ 75 years). Older subjects presented more comorbidities and tumors were located mainly in right colon (45.7%). After matching, no between-group differences in surgical postoperative complications were observed. The 30-day mortality rate was 5.3% for the older and 0.8% for the non-older group (p < 0.001). In multivariable analysis, the independent risk factors for postoperative complications were peripheral vascular disease, chronic pulmonary disease, severe liver disease, postoperative transfusion, and surgical approach. Independent risk factors for 30-day mortality were age ≥ 80 years, cerebrovascular disease, severe liver disease, and postoperative transfusion. The model was internally and externally validated, showing high accuracy. CONCLUSION: Patients aged ≥ 75 years had similar postoperative complications but higher 30-day mortality than their younger counterparts. Patients with peripheral vascular disease, chronic pulmonary disease, or severe liver disease should be informed of higher postoperative complications. But patients aged ≥ 80 suffering cerebrovascular disease, severe liver disease, or needing postoperative transfusion should be warned of significantly increased risk of postoperative mortality.

Short-Chain Fatty Acids Modulate Healthy Gut Microbiota Composition and Functional Potential.

Many studies have focused on the metabolic capacity of human gut microbiota to produce short-chain fatty acids and subsequent effects on host physiology. Given scarce data on how SCFAs produced by gut bacteria participate in cross-feeding to influence community structure and function, we evaluated the potential of SCFAs to modulate human gut microbiota in vitro. We employed anaerobic fecal cultivation in chemically defined medium supplemented with one of nine SCFAs to determine effects on both gut microbial community structure via 16S rRNA sequencing and function via genome reconstruction analysis. Each SCFA displayed significant and unique modulatory potential with respect to the relative abundance of bacterial taxa. Analysis of SCFA-supplemented communities revealed that alterations of individual closely related phylotypes displayed coherent changes, although exceptions were also observed which suggest strain-dependent differences in SCFA-induced changes. We used genome reconstruction to evaluate the functional implications of SCFA-mediated restructuring of fecal communities. We note that some SCFA-supplemented cultures displayed a reduction in the predicted abundance of SCFA producers, which suggests a possible undefined negative feedback mechanism. We conclude that SCFAs are not simply end-products of metabolism but also serve to modulate the gut microbiota through cross-feeding that alters the fitness of specified taxa. These results are important in the identification of prebiotics that elevate specific SCFAs for therapeutic benefit and highlight SCFA consumers as a salient part of the overall metabolic flux pertaining to bacterial fermentative processes.

Upregulation of the Long Noncoding RNA CASC10 Promotes Cisplatin Resistance in High-Grade Serous Ovarian Cancer.

Despite initial responses to first-line treatment with platinum and taxane-based combination chemotherapy, most high-grade serous ovarian carcinoma (HGSOC) patients will relapse and eventually develop a cisplatin-resistant fatal disease. Due to the lethality of this disease, there is an urgent need to develop improved targeted therapies against HGSOC. Herein, we identified CASC10, a long noncoding RNA upregulated in cisplatin-resistant ovarian cancer cells and ovarian cancer patients. We performed RNA sequencing (RNA-seq) in total RNA isolated from the HGSOC cell lines OVCAR3 and OV-90 and their cisplatin-resistant counterparts. Thousands of RNA transcripts were differentially abundant in cisplatin-sensitive vs. cisplatin-resistant HGSOC cells. Further data filtering unveiled CASC10 as one of the top RNA transcripts significantly increased in cisplatin-resistant compared with cisplatin-sensitive cells. Thus, we focused our studies on CASC10, a gene not previously studied in ovarian cancer. SiRNA-mediated CASC10 knockdown significantly reduced cell proliferation and invasion; and sensitized cells to cisplatin treatment. SiRNA-mediated CASC10 knockdown also induced apoptosis, cell cycle arrest, and altered the expression of several CASC10 downstream effectors. Multiple injections of liposomal CASC10-siRNA reduced tumor growth and metastasis in an ovarian cancer mouse model. Our results demonstrated that CASC10 levels mediate the susceptibility of HGSOC cells to cisplatin treatment. Thus, combining siRNA-mediated CASC10 knockdown with cisplatin may represent a plausible therapeutic strategy against HGSOC.

Analysis of SARS-CoV-2 mutations in Mexico, Belize, and isolated regions of Guatemala and its implication in the diagnosis.

The genomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide are publicly available and are derived from studies due to the increase in the number of cases. The importance of study of mutations is related to the possible virulence and diagnosis of SARS-CoV-2. To identify circulating mutations present in SARS-CoV-2 genomic sequences in Mexico, Belize, and Guatemala to find out if the same strain spread to the south, and analyze the specificity of the primers used for diagnosis in these samples. Twenty three complete SARS-CoV-2 genomic sequences, available in the GISAID database from May 8 to September 11, 2020 were analyzed and aligned versus the genomic sequence reported in Wuhan, China (NC_045512.2), using Clustal Omega. Open reading frames were translated using the ExPASy Translate Tool and UCSF Chimera (v.1.12) for amino acid substitutions analysis. Finally, the sequences were aligned versus primers used in the diagnosis of COVID-19. One hundred and eighty seven distinct variants were identified, of which 102 are missense, 66 synonymous and 19 noncoding. P4715L and P5828L substitutions in replicase polyprotein were found, as well as D614G in spike protein and L84S in ORF8 in Mexico, Belize, and Guatemala. The primers design by CDC of United States showed a positive E value. The genomic sequences of SARS-CoV-2 in Mexico, Belize, and Guatemala present similar mutations related to a virulent strain of greater infectivity, which could mean a greater capacity for inclusion in the host genome and be related to an increased spread of the virus in these countries, furthermore, its diagnosis would be affected.

Gut microbiota dysbiosis is associated with worse emotional states in HIV infection.

The biological mechanisms underlying emotional distress in HIV infection are likely to be complex but remain understudied. We investigated whether dysbiotic signatures in the gut microbiome of persons living with HIV (PLWH) are associated with their emotional status. We retrospectively examined the gut microbiome and clinical evaluation of 129 adults (94 PLWH and 35 HIV-) enrolled at UC San Diego's HIV Neurobehavioral Research Program. A subset of participants (32 PLWH vs. 13 HIV-) underwent an emotional assessment using the NIH Toolbox Emotion Battery summarized by three composite scores (negative affect, social satisfaction, and psychological well-being). We then sequenced the 16S rDNA V3-V4 regions from stool and performed taxonomic assignment using CLC Microbial Genomics Module. The gut microbiota profiles were evaluated in relation to participants' emotional assessment. All analyses were done in R statistical software. We found that the relative abundance of aerotolerant bacteria was significantly higher in PLWH (p < 0.01) and was associated with a lifetime major depression diagnosis independently of HIV status (p = 0.05). Moreover, PLWH experienced significantly worse psychological well-being (p = 0.02), less social satisfaction (p = 0.03), and more negative affect (p = 0.02). Higher levels of aerotolerant bacteria were associated with worse psychological well-being (rho = -0.35, p = 0.02), less social satisfaction (r = - 0.42, p < 0.01), and more negative affect (rho = 0.46, p < 0.01). The association of aerotolerant bacteria with social satisfaction and negative affect was independent of HIV status (p < 0.05, for both). The over-representation of aerotolerant bacteria in the gut may reflect worse oxidative stress and barrier defects and may contribute to emotional distress during HIV infection.