Renal Transplantation Enhances the Sildenafil Citrate Effectiveness in Patients with Erectile Dysfunction. A Single-Center Perspective.

OBJECTIVE: To assess the efficacy and safety of Sildenafil citrate in the treatment of ED in (HD) compared to post-RT patients. PATIENTS AND METHODS: A concurrent cohort prospective study to evaluate the efficacy of Sildenafil in the treatment of ED in 24 HD patients (Group A) and 13 patients with persistent ED one-year post-RT (Group B). The initial dose of Sildenafil was 25 mg, increased to 50 mg if there is an adequate response. An Arabic-translated International Index of Erectile Function (IIEF) questionnaire was completed one week before and after Sildenafil treatment. An IIEF erectile function score of 26 or an improvement of at least 10 points for the total IIEF score was considered a favorable response to Sildenafil. RESULTS: Group A included 22 patients with a mean age of 47.32 ± 7.013 years, whereas Group B included 13 patients with a mean age of 56.87 ± 9.612 years. The overall efficacy rate of Sildenafil was 40.9% and 76.9% in groups A and B, respectively. The post-treatment IIEF5-15 score increased from 11.1 ± 5.99 to 12.5 ± 6.41 (p = .458) and from 11.82 ± 7.534 to 21.91 ± 5.700 (p = .002) in groups A and B, respectively. In both groups, the duration of HD had no impact on ED improvement except in the post-RT non-responder subgroup. Hypertension, gastrointestinal symptoms, and flushing were both groups' most common side effects. CONCLUSION: RT could enhance the response to sildenafil in treating patients with ED. The outcome is better in younger post-RT patients with moderate and severe erectile dysfunction and shorter dialysis duration.

Attitudes toward colorectal cancer and colonoscopy in Palestine: a questionnaire-based study.

Colorectal cancer (CRC) is a frequent cause of cancer-related mortality in the Palestinian population. This cross-sectional study was conducted from July 2019 to March 2020 and examined attitudes toward CRC and colonoscopy, as well as the interplay between both. Participants were recruited using convenience sampling from public spaces, governmental hospitals, and primary healthcare centers across 11 governorates in Palestine. Displaying a positive attitude was defined as agreeing on at least the median number of questions related to CRC (5 of 11 questions) or colonoscopy (6 of 10 questions). A total of 4623 participants were included. Most participants agreed that 'early detection of CRC increases the possibility of more effective treatment' (n = 4161, 89.7%). Similarly, the majority of participants agreed on 'preferring a physician with a gender similar to the participants to perform the colonoscopy' (n = 3738, 80.9%) and 'willingness to have colonoscopy even if the participant had to pay for it' (n = 3727, 80.6%). Furthermore, 3115 participants (67.4%) demonstrated positive attitudes toward CRC, while 2540 participants (55.0%) displayed similar attitudes toward colonoscopy. Participants from the West Bank and Jerusalem were more likely than those from the Gaza Strip to display positive attitudes toward colonoscopy (59.2% vs. 48.9%). Participants with positive attitudes toward CRC were more likely to also display positive attitudes toward colonoscopy and vice versa. About two thirds of study participants exhibited positive attitudes toward CRC, and 55.0% displayed positive attitudes toward colonoscopy. There was a reciprocal relationship between having positive attitudes toward CRC and colonoscopy.

Knowledge, Attitudes, and Practices Related to Colorectal Cancer's Prevention and Early Detection Among Older Adults in Kuwait: A Cross-Sectional Study.

BACKGROUND: Worldwide, colorectal cancer is one of the significant public health concerns that imposes a substantial risk of morbidity and mortality. Early detection and management of colorectal cancer are necessary to improve the patient's prognosis and outcomes. Hence, several guidelines recommend screening patients at risk of colorectal cancer periodically. Patients' knowledge and attitudes toward screening measures influence their compliance with the guidelines. This study aimed to determine knowledge, attitudes, and practices related to prevention and early detection among older adults in Kuwait. METHODS: A cross-sectional study was conducted among Kuwaiti adults aged between 45 and 75 years attending the outpatient department in Kuwait's seven major hospitals. A convenience sampling technique was used to recruit the participants. A self-administered questionnaire consisted of four parts: sociodemographic and baseline characteristics, knowledge of colorectal cancer screening, attitudes toward colorectal cancer screening, and practices toward colorectal cancer screening. RESULTS: A total of 570 Kuwaiti patients were included, and half of them were males (n = 285). Most patients were aged between 45 and 50 years (53.8%), had a secondary school certificate (n = 357, 62.6%), and were unmarried (n = 419, 73.5%). Low levels of knowledge (<50%) and practices (<30%) toward colorectal cancer screening were seen among the participants. Statistically significant correlations were found between patients' knowledge about colorectal cancer screening and their attitudes (r = 0.317, P < 0.001) and practices (r = 0.330, P < 0.001). In addition, a moderately significant association was found between patients' attitudes and practices toward colorectal cancer screening. CONCLUSION: The study found that despite positive attitudes, Kuwaiti patients have low levels of knowledge and practice regarding colorectal cancer screening. This suggests a need for targeted, culturally sensitive educational programs and national campaigns to improve screening rates and address knowledge gaps.

Unleashing the biomimetic targeting potential of platelet-derived nanocarriers on atherosclerosis.

Atherosclerosis, the primary mechanism underlying the development of many cardiovascular illnesses, continues to be one of the leading causes of mortality worldwide. Platelet (PLT), which are essential for maintaining body homeostasis, have been strongly linked to the onset of atherosclerosis at various stages due to their inherent tendency to bind to atherosclerotic lesions and show an affinity for plaques. Therefore, mimicking PLT's innate adhesive features may be necessary to effectively target plaques. PLT-derived nanocarriers have emerged as a promising biomimetic targeting strategy for treating atherosclerosis due to their numerous advantages. These advantages include excellent biocompatibility, minimal macrophage phagocytosis, prolonged circulation time, targeting capability for impaired vascular sites, and suitability as carriers for anti-atherosclerotic drugs. Herein, we discuss the role of PLT in atherogenesis and propose the design of nanocarriers based on PLT-membrane coating and PLT-derived vesicles. These nanocarriers can target multiple biological elements relevant to plaque development. The review also emphasizes the current challenges and future research directions for the effective utilization of PLT-derived nanocarriers in treating atherosclerosis.

Differences in colorectal cancer awareness between screening eligible vs. ineligible Palestinians: a national cross-sectional study.

BACKGROUND: This study aimed to compare colorectal cancer (CRC) awareness between screening-eligible and ineligible individuals in Palestine. METHODS: Convenience sampling was utilized to recruit Palestinian adults from diverse settings, including hospitals, primary healthcare centers and public spaces across 11 governorates. The evaluation of CRC awareness in terms of signs/symptoms, risk factors and causation myths was conducted using Arabic-translated, modified versions of the validated instruments, the Bowel Cancer Awareness Measure and the Cancer Awareness Measure-Mythical Causes Scale. RESULTS: The final analysis included 2698 participants, with 2158 (80.9%) eligible for CRC screening and 540 (19.1%) ineligible for it. The most recognized CRC sign/symptom was 'lump in the abdomen' in both screening-eligible (n = 386, 71.5%) and ineligible (n = 1582, 73.3%) groups. 'Lack of physical activity' was the most recognized risk factor in both groups (eligible: n = 451, 83.5%; ineligible: n = 1766, 81.8%). The most reported causation myth in both groups was 'having a physical trauma' (eligible: n = 340, 63.0%; ineligible: n = 1353, 62.7%). In the screening-eligible group, only 210 participants (38.9%) demonstrated high awareness of CRC signs/symptoms, 213 participants (39.4%) showed high awareness of CRC risk factors and only 46 participants (8.5%) displayed high awareness of CRC causation myths. There were no significant associations between being eligible for screening colonoscopy and the awareness levels of CRC signs/symptoms, risk factors and causation myths. CONCLUSION: Overall, awareness levels of CRC signs/symptoms, risk factors and causation myths were notably low among screening-eligible participants. There were no differences in awareness levels between individuals eligible for colonoscopy and those who were not.

Functional and biochemical characterisation of remote homologues of type IV pili proteins PilN and PilO in Helicobacter pylori.

Helicobacter pylori encodes homologues of PilM, PilN and PilO from bacteria with Type IV pili, where these proteins form a pilus alignment complex. Inactivation of pilO changes H. pylori motility in semi-solid media, suggesting a link to the chemosensory pathways or flagellar motor. Here, we showed that mutation of the pilO or pilN gene in H. pylori strain SS1 reduced the mean linear swimming speed in liquid media, implicating PilO and PilN in the function, or regulation of, the flagellar motor. We also demonstrated that the soluble variants of H. pylori PilN and PilO share common biochemical properties with their Type IV pili counterparts which suggests their adapted function in the bacterial flagellar motor may be similar to that in the Type IV pili.

The Prevalence of Risk Factors for Cardiovascular Diseases in Najran Region, Saudi Arabia.

The primary goal of this study was to investigate the knowledge, prevalence, and risk factors of cardiovascular diseases among individuals in the Najran region of Saudi Arabia. In the Najran region of Saudi Arabia, an online cross-sectional survey was conducted. Between September and October 2023, a self-administered questionnaire was distributed to a random sample of the general population aged 18 and up. The survey instrument asked about history and exposure, physician-diagnosed illnesses, cardiovascular diseases (CVDs), medication use, and other risk factors. This research had a total of 2046 individuals. Around one-fifth of the study participants reported that they or a family member suffered from CVD, and arrhythmia was the most commonly reported; blood tests, cardiac catheterization, and ECG were the most commonly reported tests performed for CVD patients, around one-tenth of CVD patients reported that they do not have any chronic diseases other than CVD, and the vast majority of the patients confirmed their regular medical appointments. This is one of the first studies to investigate the knowledge, prevalence, and use of CVD drugs among individuals in the Najran region of Saudi Arabia. The study participants' lack of knowledge about CVD could lead to ineffective preventive measures and poor patient outcomes. The study's findings underscore the crucial need for more extensive and efficient educational initiatives that consider the targeted population's talents, attitudes, and perceptions.

Chitosan-Based Nanocarriers for Pulmonary and Intranasal Drug Delivery Systems: A Comprehensive Overview of their Applications.

The optimization of respiratory health is important, and one avenue for achieving this is through the application of both Pulmonary Drug Delivery System (PDDS) and Intranasal Delivery (IND). PDDS offers immediate delivery of medication to the respiratory system, providing advantages, such as sustained regional drug concentration, tunable drug release, extended duration of action, and enhanced patient compliance. IND, renowned for its non-invasive nature and swift onset of action, presents a promising path for advancement. Modern PDDS and IND utilize various polymers, among which Chitosan (CS) stands out. CS is a biocompatible and biodegradable polysaccharide with unique physicochemical properties, making it well-suited for medical and pharmaceutical applications. The multiple positively charged amino groups present in CS facilitate its interaction with negatively charged mucous membranes, allowing CS to adsorb easily onto the mucosal surface. In addition, CS-based nanocarriers have been an important topic of research. Polymeric Nanoparticles (NPs), liposomes, dendrimers, microspheres, nanoemulsions, Solid Lipid Nanoparticles (SLNs), carbon nanotubes, and modified effective targeting systems compete as important ways of increasing pulmonary drug delivery with chitosan. This review covers the latest findings on CS-based nanocarriers and their applications.

CLU (clusterin) and PPARGC1A/PGC1α coordinately control mitophagy and mitochondrial biogenesis for oral cancer cell survival.

Mitophagy involves the selective elimination of defective mitochondria during chemotherapeutic stress to maintain mitochondrial homeostasis and sustain cancer growth. Here, we showed that CLU (clusterin) is localized to mitochondria to induce mitophagy controlling mitochondrial damage in oral cancer cells. Moreover, overexpression and knockdown of CLU establish its mitophagy-specific role, where CLU acts as an adaptor protein that coordinately interacts with BAX and LC3 recruiting autophagic machinery around damaged mitochondria in response to cisplatin treatment. Interestingly, CLU triggers class III phosphatidylinositol 3-kinase (PtdIns3K) activity around damaged mitochondria, and inhibition of mitophagic flux causes the accumulation of excessive mitophagosomes resulting in reactive oxygen species (ROS)-dependent apoptosis during cisplatin treatment in oral cancer cells. In parallel, we determined that PPARGC1A/PGC1α (PPARG coactivator 1 alpha) activates mitochondrial biogenesis during CLU-induced mitophagy to maintain the mitochondrial pool. Intriguingly, PPARGC1A inhibition through small interfering RNA (siPPARGC1A) and pharmacological inhibitor (SR-18292) treatment counteracts CLU-dependent cytoprotection leading to mitophagy-associated cell death. Furthermore, co-treatment of SR-18292 with cisplatin synergistically suppresses tumor growth in oral cancer xenograft models. In conclusion, CLU and PPARGC1A are essential for sustained cancer cell growth by activating mitophagy and mitochondrial biogenesis, respectively, and their inhibition could provide better therapeutic benefits against oral cancer.

High-pressure Synthesis of Cobalt Polynitrides: Unveiling Intriguing Crystal Structures and Nitridation Behavior.

In this study, we conduct extensive high-pressure experiments to investigate phase stability in the cobalt-nitrogen system. Through a combination of synthesis in a laser-heated diamond anvil cell, first-principles calculations, Raman spectroscopy, and single-crystal X-ray diffraction, we establish the stability fields of known high-pressure phases, hexagonal NiAs-type CoN, and marcasite-type CoN2 within the pressure range of 50-90 GPa. We synthesize and characterize previously unknown nitrides, Co3N2, Pnma-CoN and two polynitrides, CoN3 and CoN5, within the pressure range of 90-120 GPa. Both polynitrides exhibit novel types of polymeric nitrogen chains and networks. CoN3 feature branched-type nitrogen trimers (N3) and CoN5 show π-bonded nitrogen chain. As the nitrogen content in the cobalt nitride increases, the CoN6 polyhedral frameworks transit from face-sharing (in CoN) to edge-sharing (in CoN2 and CoN3), and finally to isolated (in CoN5). Our study provides insights into the intricate interplay between structure evolution, bonding arrangements, and high-pressure synthesis in polynitrides, expanding the knowledge for the development of advanced energy materials.

The dicot homolog of maize PPR103 carries a C-terminal DYW domain and may have a role in C-to-U editing of some chloroplast RNA transcripts.

In plants, cytidine-to-uridine (C-to-U) editing is a crucial step in processing mitochondria- and chloroplast-encoded transcripts. This editing requires nuclear-encoded proteins including members of the pentatricopeptide (PPR) family, especially PLS-type proteins carrying the DYW domain. IPI1/emb175/PPR103 is a nuclear gene encoding a PLS-type PPR protein essential for survival in Arabidopsis thaliana and maize. Arabidopsis IPI1 was identified as likely interacting with ISE2, a chloroplast-localized RNA helicase associated with C-to-U RNA editing in Arabidopsis and maize. Notably, while the Arabidopsis and Nicotiana IPI1 orthologs possess complete DYW motifs at their C-termini, the maize homolog, ZmPPR103, lacks this triplet of residues which are essential for editing. In this study we examined the function of IPI1 in chloroplast RNA processing in N. benthamiana to gain insight into the importance of the DYW domain to the function of the EMB175/PPR103/ IPI1 proteins. Structural predictions suggest that evolutionary loss of residues identified as critical for catalyzing C-to-U editing in other members of this class of proteins, were likely to lead to reduced or absent editing activity in the Nicotiana and Arabidopsis IPI1 orthologs. Virus-induced gene silencing of NbIPI1 led to defects in chloroplast ribosomal RNA processing and changes to stability of rpl16 transcripts, revealing conserved function with its maize ortholog. NbIPI1-silenced plants also had defective C-to-U RNA editing in several chloroplast transcripts, a contrast from the finding that maize PPR103 had no role in editing. The results indicate that in addition to its role in transcript stability, NbIPI1 may contribute to C-to-U editing in N. benthamiana chloroplasts.

Distinct functional neutrophil phenotypes in sepsis patients correlate with disease severity.

Purpose: Sepsis is a clinical syndrome defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis is a highly heterogeneous syndrome with distinct phenotypes that impact immune function and response to infection. To develop targeted therapeutics, immunophenotyping is needed to identify distinct functional phenotypes of immune cells. In this study, we utilized our Organ-on-Chip assay to categorize sepsis patients into distinct phenotypes using patient data, neutrophil functional analysis, and proteomics. Methods: Following informed consent, neutrophils and plasma were isolated from sepsis patients in the Temple University Hospital ICU (n=45) and healthy control donors (n=7). Human lung microvascular endothelial cells (HLMVEC) were cultured in the Organ-on-Chip and treated with buffer or cytomix ((TNF/IL-1ß/IFNγ). Neutrophil adhesion and migration across HLMVEC in the Organ-on-Chip were used to categorize functional neutrophil phenotypes. Quantitative label-free global proteomics was performed on neutrophils to identify differentially expressed proteins. Plasma levels of sepsis biomarkers and neutrophil extracellular traps (NETs) were determined by ELISA. Results: We identified three functional phenotypes in critically ill ICU sepsis patients based on ex vivo neutrophil adhesion and migration patterns. The phenotypes were classified as: Hyperimmune characterized by enhanced neutrophil adhesion and migration, Hypoimmune that was unresponsive to stimulation, and Hybrid with increased adhesion but blunted migration. These functional phenotypes were associated with distinct proteomic signatures and differentiated sepsis patients by important clinical parameters related to disease severity. The Hyperimmune group demonstrated higher oxygen requirements, increased mechanical ventilation, and longer ICU length of stay compared to the Hypoimmune and Hybrid groups. Patients with the Hyperimmune neutrophil phenotype had significantly increased circulating neutrophils and elevated plasma levels NETs. Conclusion: Neutrophils and NETs play a critical role in vascular barrier dysfunction in sepsis and elevated NETs may be a key biomarker identifying the Hyperimmune group. Our results establish significant associations between specific neutrophil functional phenotypes and disease severity and identify important functional parameters in sepsis pathophysiology that may provide a new approach to classify sepsis patients for specific therapeutic interventions.

Recurrent ATP1A1 variant Gly903Arg causes developmental delay, intellectual disability, and autism.

ATP1A1 encodes a sodium-potassium ATPase that has been linked to several neurological diseases. Using exome and genome sequencing, we identified the heterozygous ATP1A1 variant NM_000701.8: c.2707G>A;p.(Gly903Arg) in two unrelated children presenting with delayed motor and speech development and autism. While absent in controls, the variant occurred de novo in one proband and co-segregated in two affected half-siblings, with mosaicism in the healthy mother. Using a specific ouabain resistance assay in mutant transfected HEK cells, we found significantly reduced cell viability. Demonstrating loss of ATPase function, we conclude that this novel variant is pathogenic, expanding the phenotype spectrum of ATP1A1.

Evaluation of Olfactory Dysfunction Among COVID-19 Patients in Baghdad, Iraq.

Background SARS­CoV­2 (COVID-19) causes olfactory dysfunction which is characterized by anosmia or hyposmia. Characterization of olfactory dysfunction has added value to the diagnosis and prognosis of the disease. Nevertheless, scarce information exists about COVID-19 patients suffering from olfactory dysfunction in Iraq. This study aimed to identify olfactory dysfunction (anosmia or hyposmia) in Iraqi COVID-19 patients and examine their response to smell exercise at Baghdad Medical City Complex, Baghdad, Iraq. Methodology This case series prospective study involving 300 patients (160 males and 140 females) with COVID-19 infection was conducted from June 1, 2020, to October 1, 2021. We recorded signs and symptoms of COVID-19 among patients by examining olfactory dysfunction, n-butanol olfaction test, and smell test exercise. Results Anosmia and hyposmia were found in 69.3% and 30.7% of the patients, respectively; of these, 65.7% were of sudden onset. The association between olfactory dysfunction and smoking was not significant. The most frequent signs and symptoms of COVID-19 were fatigue, fever, loss of taste, myalgia, headache, sore throat, cough, depressed appetite, dyspnea, nausea, abdominal pain, and diarrhea. The highest frequencies of occurrence of anosmia (30.7%) and hyposmia (13.3%) were in the age group of 31-40 years. The majority (47.7%) of patients with olfactory dysfunction recovered within one month of COVID-19 onset. The rest of the patients recovered within one month to 16 months. The most commonly encountered ear, nose, and throat symptoms were nasal obstruction, rhinorrhea, and facial/ear pain. The percentages of patients with anosmia and hyposmia recovering with smell exercise were significant at 64.7% and 25.3%, respectively. Conclusions The prognosis of olfactory dysfunction in COVID-19 patients was good as most cases recovered within a short period with concomitant smell exercise. Olfactory dysfunction in the majority of COVID-19 patients was self-limiting in young age groups, albeit in association with the non-severity of the disease. Being an important public health issue, examining olfactory dysfunction aspects should be considered in the diagnosis, prognosis, and treatment protocols of COVID-19 patients. In-depth exploration is needed to examine olfactory and gustatory dysfunction in patients suffering from severe COVID-19.

Screening Perspectives: The Role of Colorectal Cancer Awareness in Shaping Attitudes Toward Colonoscopy in Palestine.

PURPOSE: To assess colorectal cancer (CRC) awareness and its influence on attitudes toward colonoscopy in Palestine. MATERIALS AND METHODS: Convenience sampling was used to recruit Palestinian adults from hospitals, primary health care centers, and public spaces across 11 governorates. To evaluate the awareness of CRC signs/symptoms, risk factors, and mythical causes, the Bowel Cancer Awareness Measure and Cancer Awareness Measure-Mythical Causes Scale were used after translation into Arabic. For each correctly recognized item, one point was given. The total awareness score of each domain was calculated and categorized into tertiles; the top tertile was considered high awareness, and the other two tertiles were considered low awareness. RESULTS: A total of 4,623 questionnaires were included. Only 1,849 participants (40.0%) exhibited high awareness of CRC signs/symptoms. High awareness of CRC symptoms was associated with higher likelihood of showing positive attitudes toward colonoscopy (odds ratio [OR], 1.21 [95% CI, 1.07 to 1.37]). A total of 1,840 participants (38.9%) demonstrated high awareness of CRC risk factors. Participants with high awareness of CRC risk factors were more likely to display positive attitudes toward colonoscopy (OR, 1.20 [95% CI, 1.07 to 1.37]). Only 219 participants (4.7%) demonstrated high awareness of CRC causation myths. There was no association between awareness of CRC causation myths and positive attitudes toward colonoscopy. CONCLUSION: Awareness of CRC was poor with less than half of the study participants demonstrating high awareness of CRC signs/symptoms and risk factors, and a minority (<5%) displaying high awareness of CRC causation myths. High awareness of CRC signs/symptoms and risk factors was associated with greater likelihood of demonstrating positive attitudes toward colonoscopy. Educational initiatives are needed to address knowledge gaps and dispel misconceptions surrounding CRC.

Differences in Colorectal Cancer Awareness Between Vegetarians and Nonvegetarians: A National Cross-Sectional Study From Palestine.

PURPOSE: To compare colorectal cancer (CRC) awareness between vegetarians and nonvegetarians in Palestine. MATERIALS AND METHODS: The validated Bowel Cancer Awareness Measure and Cancer Awareness Measure-Mythical Causes Scale were translated into Arabic and used to assess awareness of CRC signs/symptoms, risk factors, and mythical causes. The total awareness score of each domain was calculated and categorized into tertiles; the top tertile was considered as good awareness. Multivariable logistic regression analysis was used to examine the association between being a vegetarian and displaying good awareness in each domain. RESULTS: This study included 4,623 participants: 560 vegetarians (12.1%) and 4,063 nonvegetarians (87.9%). Lump in the abdomen was the most recognized CRC sign/symptom among both nonvegetarians (n = 2,969, 73.1%) and vegetarians (n = 452, 80.7%). Vegetarians were less likely than nonvegetarians to display good awareness of CRC signs/symptoms (odds ratio, 0.59 [95% CI, 0.48 to 0.72]). Lack of physical activity was the most identified modifiable CRC risk factor in both nonvegetarians (n = 3,368, 82.9%) and vegetarians (n = 478, 85.4%). Similarly, having a bowel disease was the most identified nonmodifiable risk factor among both nonvegetarians (n = 2,889, 71.1%) and vegetarians (n = 431, 77.0%). There were no associated differences between both groups in the awareness levels of CRC risk factors. The most recognized food-related CRC causation myth in nonvegetarians was drinking from plastic bottles (n = 1,023, 25.2%), whereas it was eating burnt food in vegetarians (n = 176, 31.4%). Having a physical trauma was the most recognized food-unrelated myth in both nonvegetarians (n = 2,356, 58.0%) and vegetarians (n = 396, 70.7%). There were no associated differences in the awareness of CRC causation myths between both groups. CONCLUSION: Awareness of CRC was notably low in both Palestinian vegetarians and nonvegetarians. Particularly, vegetarians demonstrated lower awareness of CRC signs and symptoms.

Molecular identification and whole genome sequence analyses of methicillin-resistant and mastitis-associated Staphylococcus aureus sequence types 6 and 2454 isolated from dairy cows.

The emergence of antimicrobial-resistant and mastitis-associated Staphylococcus aureus is of great concern due to the huge economic losses worldwide. Here, we report draft genome sequences of two Staphylococcus aureus strains which were isolated from raw milk samples obtained from mastitis-infected cows in Bangladesh. The strains were isolated and identified using conventional microbiological and molecular polymerase chain reaction (PCR) methods. Antibiotic susceptibility testing was performed. Genomic DNA of the two strains was extracted and the strains were sequenced using the Illumina NextSeq 550 platform. The assembled contigs were analyzed for virulence determinants, antimicrobial resistance genes, extra-chromosomal plasmids, and multi-locus sequence type (MLST). The genomes of the two strains were compared with other publicly available genome sequences of Staphylococcus aureus strains. The raw read sequences were downloaded and all sequence files were analyzed identically to generate core genome phylogenetic trees. The genome of BR-MHR281strain did not harbour any antibiotic resistance determinants, however BR-MHR220 strain harbored mecA and blaZ genes. Analysis of BR-MHR220 strain revealed that it was assigned to sequence type (ST-6), clonal complex (CC) 5 and spa type t304, while BR-MHR281 strain belonged to ST-2454, CC8, and harbored the spa type t7867. The findings of the present study and the genome sequences of BR-MHR220 and BR-MHR281 strains will provide data on the detection and genomic analysis and characterization of mastitis-associated Staphylococcus aureus in Bangladesh. In addition, the findings of the present study will serve as reference genomes for future molecular epidemiological studies and will provide significant data which help understand the prevalence, pathogenesis and antimicrobial resistance of mastitis-associated Staphylococcus aureus.

Folliculin gene-negative Birt-Hogg-Dube syndrome: a case report.

Introduction and importance: Birt-Hogg-Dube (BHD) is a rare genetic disorder that results from a mutation in the folliculin (FLCN) gene. Manifestations include pulmonary cysts, fibrofolliculomas, renal tumors, and pneumothoraces. Genetic testing can be used to confirm the diagnosis when suspected. BHD syndrome is diagnosed in patients with negative FLCN gene results using diagnostic criteria. Case presentation: A male in his 20s presented with recurrent pneumothoraces. A physical examination revealed bumps on his face and upper body. A chest computed tomography scan revealed cystic lesions. Blood tests, ESR, and CRP levels were unremarkable. Punch skin biopsy revealed fibrofolliculomas. Genetic testing for the FLCN mutation returned negative. His history, physical exam, imaging, and histopathology suggested BHD syndrome despite having a negative family history and genetic analysis. Eventually, the patient was diagnosed with FLCN gene-negative BHD syndrome. Clinical discussion: More than a hundred families have been identified to have BHD worldwide. There are a few cases in the literature describing patients phenotypically presenting with BHD despite having a negative genetic analysis. One study in Japan found 16 out of 157 individuals having a clinical presentation of BHD with no mutations. Also, decreased expression of the FLCN mRNA may lead to BHD. Conclusion: BHD syndrome can present with a negative FLCN gene mutation; however, patients must meet the known diagnostic criteria such as criteria made by Menko et al., Gupta et al., and Schmidt et al. in order to have a diagnosis of BHD syndrome. Also, a qualitative decrease of FLCN with the absence of mutations may also lead to BHD.

ADAMTSL2 mutations determine the phenotypic severity in geleophysic dysplasia.

Geleophysic dysplasia-1 (GD1) is an autosomal recessive disorder caused by ADAMTS-like 2 (ADAMTSL2) variants. It is characterized by distinctive facial features, limited joint mobility, short stature, brachydactyly, and life-threatening cardiorespiratory complications. The clinical spectrum spans from perinatal lethality to milder adult phenotypes. We developed and characterized cellular and mouse models, to replicate the genetic profile of a patient who is compound heterozygous for 2 ADAMTSL2 variants, namely p.R61H and p.A165T. The impairment of ADAMTSL2 secretion was observed in both variants, but p.A165T exhibited a more severe impact. Mice carrying different allelic combinations revealed a spectrum of phenotypic severity, from lethality in knockout homozygotes to mild growth impairment observed in adult p.R61H homozygotes. Homozygous and hemizygous p.A165T mice survived but displayed severe respiratory and cardiac dysfunction. The respiratory dysfunction mainly affected the expiration phase, and some of these animals had microscopic post-obstructive pneumonia. Echocardiograms and MRI studies revealed a significant systolic dysfunction, accompanied by a reduction of the aortic root size. Histology verified the presence of hypertrophic cardiomyopathy with myocyte hypertrophy, chondroid metaplasia, and mild interstitial fibrosis. This study revealed a substantial correlation between the degree of impaired ADAMTSL2 secretion and the severity of the observed phenotype in GD1.

Retraction: Isolated Polycystic Liver Disease: A Rare Genetic Disorder.

[This retracts the article DOI: 10.7759/cureus.18560.].