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• 30 patients with Takotsubo syndrome underwent coronary angiography and invasive evaluation of microvascular function. • 83 % of the patients had at least one abnormal coronary microvascular function parameter. • Resistive Reserve Ratio (RRR) may be a sensitive parameter to assess microvascular function. • Longer time from first symptoms to angiography positively correlated with higher levels of coronary flow reserve. • A non-emotional trigger for Takotsubo was associated with a pathological index of microcirculatory resistance (IMR). The pathophysiology of Takotsubo syndrome (TTS) remains incompletely understood. While coronary microvascular dysfunction (CMD) is a potential pathophysiologic mechanism, evidence is limited. We sought to evaluate CMD in patients with TTS. Consecutive patients diagnosed with TTS were included and underwent coronary angiography with invasive microvascular function evaluation, including fractional flow reserve, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR), and Resistive Reserve Ratio (RRR). Patients had an echocardiography evaluation during their index admission and at approximately 6 weeks. Thirty patients were included (mean age 74 ±9, 90 % female). Twenty-five patients (83 %) had at least one abnormal coronary microvascular function parameter. Abnormal parameters included CFR<2.5 in 20 patients (67 %), IMR>25 in 18 patients (60 %), and RRR<3.5 in 25 (83 %). Longer time from symptoms to angiography correlated with a higher CFR (r = 0.51, P<0.01), and had an area under the receiver operating characteristic curve of 0.793 (95 % CI 0.60-0.98) for pathologic CFR. Patients with emotional trigger had a lower rate of pathologic IMR compared with non-emotional trigger (36 % vs 81 %, p = 0.01). Follow up echocardiography performed at a median of 1.5 months (IQR 1.15-6) showed an improvement in left ventricular ejection fraction for all patients (from mean of 40 % to 57 %). CMD was present in most patients with TTS. The role of microvascular function in TTS may vary according to the clinical presentation and RRR may be more sensitive for the diagnosis of CMD in TTS. [ABSTRACT FROM AUTHOR]

Background: Vibrio cholerae is a primary cause of severe dehydrating diarrhea and remains a serious public health problem in low- and middleincome countries (LMICs) with insufficient water, sanitation, and hygiene. Cholera remains a public health threat the worldwide, mainly in countries with poor access to safe water and sanitation facilities. According to estimates, there are 21,000-143,000 deaths and 1.3-4 million cases of cholera annual. Objective: This study aims to carry out an analysis of the available information on cholera outbreaks in Diyala province, 2022. Patients and Methods: A descriptive study conducted in the department of public health using the data of cases reported from eight sectors in province. The data was collected from the surveillance unit, communicable control division of the public health department in Diyala province, IRAQ in 2022. Results: The total number of confirmed cases of cholera was (n = 139), female (72) 52 % and male (67) 48%, death reported for two of these cases. According to the date of onset, the registration of cases began from July 19 to October 25, 2022. However, the case fatality ratio (CFR) was 1.4%, while the attack rate in the governorate is 7.6 per 100,000 populations during 2022, the highest attack rate in Khanaqin district was (77 cases) 46, while the lowest attack rate in Baldruze, Al-Mansuria, and Al-Khalis districts was (1 case) 0.3,0.6, and 0.8 respectively. The age mean of patients was (38.7 ± 17.14 years) and the occurrence of the disease is more incidence in the age group 30-44 and females more than males. Conclusion: Occurrence Cholera outbreak during year 2022 without confirmed cases recorded since 2015 and the occurrence of cholera cases in governorate is greater during the months of August and September and most of the cases were from Khanaqin district. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to meticulously analyse the trends and recurrent challenges that emerge from Warning Letters (WLs) issued by the United States Food and Drug Administration (USFDA), focusing on current Good Manufacturing Practices (cGMP) voilations. By investigating the organizational, procedural, and systemic factors that precipitate these non-compliances, the research provides a comprehensive overview of the obstacles to cGMP adherence. Methods: The framework for this study involved a detailed statistical analysis of WLs issued from 2019 to 2024, accessible through the USFDA database. Each letter was categorized and analysed according to violation type, frequency, and underlying causes. This approach facilitated a nuanced understanding of the major and minor compliance issues affecting the pharmaceutical industry. Results: The analysis of total 186 WLs reveals a predominance of violations related to cGMP standards and adulteration of drug products, pinpointing these areas as significant compliance. The study further categorizes and discusses minor violations to offer a holistic view of the compliance landscape in pharmaceutical insdustries. Conclusion: The findings from the WLs suggests a critical need for enhanced regulatory vigilance and quality assurance processes within pharmaceutical companies. The recurrent nature of certain violations highlights potential systemic flaws in how cGMP guidelines are implemented and adhered to across the industry. This research advocates for a proactive regulatory strategy by forecasting regulatory trends and identifying cGMP enforcement challenges, aiming to strengthen quality, streamline inspections, reduce compliance discrepancies, and improve public health outcomes. [ABSTRACT FROM AUTHOR]

Background: Vibrio cholerae is a primary cause of severe dehydrating diarrhea and remains a serious public health problem in low- and middle-income countries (LMICs) with insufficient water, sanitation, and hygiene. Cholera remains a public health threat the worldwide, mainly in countries with poor access to safe water and sanitation facilities. According to estimates, there are 21,000–143,000 deaths and 1.3–4 million cases of cholera annual. Objective: This study aims to carry out an analysis of the available information on cholera outbreaks in Diyala province, 2022. Patients and Methods: A descriptive study conducted in the department of public health using the data of cases reported from eight sectors in province. The data was collected from the surveillance unit, communicable control division of the public health department in Diyala province, IRAQ in 2022. Results: The total number of confirmed cases of cholera was (n = 139), female (72) 52 % and male (67) 48%, death reported for two of these cases. According to the date of onset, the registration of cases began from July 19 to October 25, 2022. However, the case fatality ratio (CFR) was 1.4%, while the attack rate in the governorate is 7.6 per 100,000 populations during 2022, the highest attack rate in Khanaqin district was (77 cases) 46, while the lowest attack rate in Baldruze, Al-Mansuria, and Al-Khalis districts was (1 case) 0.3,0.6, and 0.8 respectively. The age mean of patients was (38.7 ± 17.14 years) and the occurrence of the disease is more incidence in the age group 30-44 and females more than males. Conclusion: Occurrence Cholera outbreak during year 2022 without confirmed cases recorded since 2015 and the occurrence of cholera cases in governorate is greater during the months of August and September and most of the cases were from Khanaqin district.

ABSTRACT: Objectives: Staphylococcus epidermidis is a member of the human skin microbiome. However, in recent decades, multidrug-resistant and hospital-adapted S. epidermidis clones are increasingly involved in severe human infections associated with medical devices and in immunocompromised patients. In 2016, we reported that a linezolid- and methicillin-resistant S. epidermidis ST2 clone, bearing the G2576T mutation, was endemic in an Italian hospital since 2004. This study aimed to retrospectively analyse 34 linezolid- and methicillin-resistant S. epidermidis (LR-MRSE) strains collected from 2018 to 2021 from the same hospital. Methods: LR-MRSE were typed by Pulsed-Field Gel Electrophoresis and multilocus sequence typing and screened for transferable linezolid resistance genes. Representative LR-MRSE were subjected to whole-genome sequencing (WGS) and their resistomes, including the presence of ribosomal mechanisms of linezolid resistance and of rpoB gene mutations conferring rifampin resistance, were investigated. Results: ST2 lineage was still prevalent (19/34; 55.9%), but, over time, ST5 clone has been widespread too (15/34; 44.1%). Thirteen of the 34 isolates (38.2%) were positive for the cfr gene. Whole-genome sequencing analysis of relevant LR-MRSE displayed complex resistomes for the presence of several acquired antibiotic resistance genes, including the SCCmec type III (3A) and SCCmec type IV (2B) in ST2 and ST5 isolates, respectively. Bioinformatics and polymerase chain reaction (PCR) mapping also showed a plasmid-location of the cfr gene and the occurrence of previously undetected mutations in L3 (ST2 lineage) and L4 (ST3 lineage) ribosomal proteins and substitutions in the rpoB gene. Conclusion: The occurrence of LR-MRSE should be carefully monitored in order to prevent the spread of this difficult-to-treat pathogen and to preserve the efficacy of linezolid.

With the advent of COVID-19 health authorities of most Top high GDP countries dominated the economy. A policy response to COVID-19 pandemic, was the lockdown policy. I show that this discretionary biological health policy in a new shopping time model by dynamic programming technique, decrease the value of transaction time saved by holding additional money and increases the real balance of money during COVID-19. An optimal monetary policy rule during COVID-19 is a rule, based on that, the growth rate of banking discount rate equals the variation of case fatality risk (CFR). This rule is computed as an optimal monetary policy rule for each month of the top 15 GDP countries of the world in 2020. The results show that the rate of rapid and hasty reduction of the announced discount rates during the COVID-19 period were not optimal and would be one of the reasons for the occurrence of inflation and the failure of the inflation target policy in recent years. Therefore, I recommend a rule to determine an optimal monetary policy when our world experiences a biological shock. [ABSTRACT FROM AUTHOR]

Regadenoson as a selective A2A adenosine enables pharmacological stress when exercise stress techniques would be impossible or very difficult. We present two case reports demonstrating its advantages. In case 1, we initially attempted to induce stress using physical exercise in a 77-year-old male patient after coronary artery bypass graft. Due to inadequate heart rate increase, the stress was promptly converted to pharmacological stress using regadenoson in combination with a low level of exercise. Single-photon emission computed tomography (SPECT) showed extensive ischaemia of the lateral wall. Coronary angiography subsequently revealed vein graft occlusion at the left circumflex artery. Case 2 demonstrates recent advances in SPECT technology. Modern multidetector Cadmium Zinc Telluride (CZT) cameras enable dynamic acquisition and quantification of coronary flow reserve (CFR). It can be helpful in identifying multivessel disease or microvascular ischaemia. CFR is calculated as the ratio between myocardial blood flow during stress vasodilator hyperaemia and flow at rest. In a 50-year-old diabetic patient, a conventional cardiac SPECT showed normal post-stress left ventricular perfusion and function. Dynamic SPECT showed normal myocardial blood flow (MBF) and normal CFR ≥ 2. During 18 months of follow-up, no cardiac event was observed in this patient. [ABSTRACT FROM AUTHOR]

Aerobic granules are small, dense aggregates of microbial cells that form naturally in aerobic wastewater treatment systems. They are characterized by their spherical shape, strong structural integrity, and ability to rapidly settle. These granules are formed through a self-immobilization process where different microbial species coalesce to degrade organic and inorganic compounds in wastewater. This study summarizes the development of aerobic granulation technology in wastewater treatment and the mechanism of aerobic granules' formation, analyzes the characteristics and the factors affecting the aerobic granules' formation, and presents practical engineering examples of its application from pilot-scale to full-scale operation. [ABSTRACT FROM AUTHOR]

This paper investigates methods for noise-canceling channel estimation (NC-CE) to track rapid time-varying channels in IEEE 802.11p/orthogonal frequency division multiplexing (OFDM) systems. To this end, we introduce a novel three-step channel estimation technique based on the estimated length of the channel impulse response (CIR). This approach aims to surpass the performance of conventional designs that rely on constructed data pilots (CDPs). In the first step, we not only eliminate noise components but also estimate the channel frequency responses (CFRs) of virtual subcarriers for long preamble parts. Moving on to the second step, we incorporate a modified CDP method without a frequency-domain reliability test and interpolation, taking into account the CFRs of virtual subcarriers obtained at the previous OFDM symbol time. The final step can be implemented as the operation of the inverse fast Fourier transform (IFFT)/nulling/FFT to reduce noise components from the CFRs obtained in the second step and generate CFRs for virtual subcarriers to be used in the next symbol time. The results of our simulations validate the effectiveness of our proposed channel estimation schemes. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus haemolyticus is a clinically significant Coagulase Negative Staphylococci (CoNS) accountable for various infections and is often multi-drug resistant along with resistance to linezolid. Aim and Objectives: This study was carried out to detect the presence of cfr and optrA gene in clinical isolates of linezolid resistant S. haemolyticus in a tertiary care hospital. Material and Methods: A total of 227 clinical isolates of S. haemolyticus recovered from various clinical samples were tested to determine susceptibility to linezolid by phenotypic method. Further, the presence of cfr & optrA gene was looked for, in clinical isolates of S. haemolyticus. Results: S. haemolyticus was isolated predominantly from inpatient department mainly from blood culture (85%). Linezolid resistance was confirmed in 9.2% isolates of S. haemolyticus phenotypically and they were also methicillin resistant. On genotypic characterization, cfr gene could be detected in 7.04% the isolates. However, all the isolates were negative for optrA gene. Conclusion: Emergence of resistance to linezolid in S. haemolyticus was reported for the first time. The presence of cfr gene is the most common mechanism of resistance to linezolid. Correct identification of these isolates and adherence to strict infection control protocols will help in better clinical outcomes.

Purpose: To investigate the effects of various intervention approaches on cancer-related fatigue (CRF) in patients with breast cancer. Method: Computer searches were conducted on PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang databases from their establishment to June 2023. Selection was made using inclusion and exclusion criteria, and 77 articles were included to compare the effects of 12 interventions on patients with breast cancer. Results: Seventy-seven studies with 12 various interventions were examined. The network findings indicated that cognitive behavioral therapy (CBT) (SMD, -1.56; 95%CI, -3.08~-0.04), Chinese traditional exercises (CTE) (SMD, -0.85; 95%CI, -1.34~-0.36), aerobic exercise (AE) (SMD, -0.77; 95%CI, -1.09~-0.45), multimodal exercise (ME) (SMD, -0.75; 95%CI, -1.26~-0.25), music interventions (MI) (SMD, -0.74; 95%CI, -1.45~-0.03), and yoga (YG) (SMD, -0.44; 95%CI, -0.83 to -0.06) can reduce CRF more than the control group (CG). For relaxation exercises (RE) (MD, -6.69; 95%CI, -9.81~-3.57), MI (MD, -5.45; 95%CI, -7.98~-2.92), AE (MD, -4.34; 95%CI, -5.90~-2.78), ME (MD, -3.47; 95%CI, -4.95~-1.99), YG (MD, -2.07; 95%CI, -3.56~-0.57), and mindfulness training (MD, -1.68; 95%CI, -2.91~-0.46), PSQI improvement was superior to CG. In addition, for CTE (MD, 11.39; 95%CI, 4.11-18.66), YG (MD, 11.28; 95%CI, 1.63-20.93), and AE (MD, 9.34; 95%CI, 0.26~18.42), Functional Assessment of Cancer Therapy-Breast improvement was superior to CG. Conclusion: Cognitive behavioral therapy (CBT) is the most effective measure for alleviating CRF in patients with breast cancer and Relaxation exercises (RE) is the most effective measure for improving sleep quality. In addition, Chinese traditional exercises (CTE) is the best measure for enhancing quality of life. Additional randomized controlled trials (RCTs) are expected to further investigate the efficacy and mechanisms of these interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Florfenicol is a synthetic analog of chloramphenicol, which is used mostly in livestock animals. Its potential as an alternative agent in companion animals is strong because of its beneficial properties, such as its extensive wide spectrum and relatively increased, compared to chloramphenicol, safety during administration. However, the emergence of resistant strains can overcome this potential. The distribution of florfenicol-resistant bacteria was investigated among multidrug-resistant (MDR) Enterobacterales isolated from diagnostic samples of companion animals in Greece, which were collected throughout the country. Data regarding sample origin, type of infection, bacterial species, and resistance profiles were assembled and compared. The presence of specific florfenicol-associated antibiotic resistance genes (ARGs) was examined, and the results were interpreted in comparison with those of antibiotic susceptibility testing (AST). The results of this study indicate that the distribution of florfenicol-resistant MDR Enterobacterales in pets throughout the country is considerable (17.9%) and mainly attributed to the plasmid-mediated floR gene. Thus, there is an increased risk of co-acquisition of florfenicol-specific ARGs through horizontal transfer, along with several other resistance genes. Even though the potential of florfenicol to constitute an alternative antibiotic in companion animals seems high, continuous monitoring of antibiotic resistance profiles is needed. Florfenicol is a promising antibiotic for use in companion animals, especially as an alternative agent for infections caused by MDR bacteria. However, the emergence of resistant strains could hinder this potential. In this study, florfenicol resistance was investigated in a total of 246 MDR Enterobacterales obtained from canine and feline clinical samples in Greece over a two-year period (October 2020 to December 2022); a total of 44 (17,9%) florfenicol-resistant strains were recognized and further investigated. Most of these isolates originated from urine (41.9%) and soft tissue (37.2%) samples; E. coli (n = 14) and Enterobacter cloacae (n = 12) were the predominant species. The strains were examined for the presence of specific florfenicol-related resistance genes floR and cfr. In the majority of the isolates (31/44, 70.5%), the floR gene was detected, whereas none carried cfr. This finding creates concerns of co-acquisition of plasmid-mediated florfenicol-specific ARGs through horizontal transfer, along with several other resistance genes. The florfenicol resistance rates in MDR isolates seem relatively low but considerable for a second-line antibiotic; thus, in order to evaluate the potential of florfenicol to constitute an alternative antibiotic in companion animals, continuous monitoring of antibiotic resistance profiles is needed in order to investigate the distribution of florfenicol resistance under pressure of administration of commonly used agents. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus haemolyticus is a clinically significant Coagulase Negative Staphylococci (CoNS) accountable for various infections and is often multi-drug resistant along with resistance to linezolid. Aim and Objectives: This study was carried out to detect the presence of cfr and optrA gene in clinical isolates of linezolid resistant S. haemolyticus in a tertiary care hospital. Material and Methods: A total of 227 clinical isolates of S. haemolyticus recovered from various clinical samples were tested to determine susceptibility to linezolid by phenotypic method. Further, the presence of cfr & optrA gene was looked for, in clinical isolates of S. haemolyticus. Results: S. haemolyticus was isolated predominantly from inpatient department mainly from blood culture (85%). Linezolid resistance was confirmed in 9.2% isolates of S. haemolyticus phenotypically and they were also methicillin resistant. On genotypic characterization, cfr gene could be detected in 7.04% the isolates. However, all the isolates were negative for optrA gene. Conclusion: Emergence of resistance to linezolid in S. haemolyticus was reported for the first time. The presence of cfr gene is the most common mechanism of resistance to linezolid. Correct identification of these isolates and adherence to strict infection control protocols will help in better clinical outcomes. [ABSTRACT FROM AUTHOR]

Power Amplifiers (PAs) play a vital role in mobile communication. However, their inherent nonlinearity can lead to issues such as unwanted radiation, interference with neighboring channels, and distortion within the desired frequency range. To address these problems, PAs are typically operated at a lower power level than their saturation point, sacrificing power efficiency to improve Error Vector Magnitude (EVM) performance. Consequently, more than 70-80% of the DC power is wasted as heat. This inefficiency necessitates the exploration of techniques to enhance PA efficiency while maintaining acceptable linearity and performance. Digital Pre-Distortion (DPD) is a useful technique to linearize PAs. DPD allows affordable nonlinear PAs to function with minimal distortion in their nonlinear operating regions. This results in amplified signals with increased power output and improved power efficiency. Using nonlinear functions, the output signal of the PA can be linearized, mitigate distortions, and be effectively optimized. When using various operating channels and varying time, temperature, and PA nonlinearity, the DPD must adjust. In order to increase the power efficiency of 5G systems, DPD-enabled systems are inculcating with adaptive DFT-s-OFDM employed 5G physical layer along with the Crest Factor Reduction (CFR) algorithm. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objectives: In contrast to increasing reports of the emergence of linezolid-resistant enterococci (LRE) emanating from many countries in Europe, Asia, and North America, data on its status and dissemination from the African continent remain scarce, with the information available limited to countries in North Africa. This study investigated the carriage of LRE and the genetic mechanism of resistance among Enterococcus faecium and Enterococcus faecalis strains recovered from humans and animals in Makurdi, Nigeria. Methods: We conducted a cross-sectional study between June 2020 and July 2021 during which 630 non-duplicate human and animal faecal samples were collected and processed for the recovery of LRE. The genetic mechanisms for resistance were investigated using polymerase chain reaction (PCR) and Sanger sequencing. Results: Linezolid-resistant enterococci were recovered from 5.87% (37/630; 95% CI: 4.17–8.00) of the samples, with the prevalence in animals and humans being 6.22% [(28/450); 95% CI: 4.17–8.87] and 5.00% [(9/180); 95% CI: 2.31–9.28], respectively. All isolates remained susceptible to vancomycin. No known point mutation mediating linezolid resistance was detected in the 23S rRNA and ribosomal protein genes; however, acquisition of one or more potentially transferable genes (cfr, optrA, and poxtA) was observed in 26 of the 37 LRE isolates. Co-existence of all three transferable genes in a single isolate was found in four E. faecium strains of animal origin. Conclusion: This study provides baseline evidence for the emergence and active circulation of LRE driven majorly by the acquisition of the optrA gene in Nigeria. To the best of our knowledge, our study is the first to report a co-carriage of all three transferable linezolid resistance determinants in E. faecium. Active LRE surveillance is urgently required to understand the extent of LRE spread across sub-Saharan Africa and to develop tailored mitigation strategies.

Alteration of antibiotic binding sites through modification of ribosomal RNA (rRNA) is a common form of resistance to ribosome-targeting antibiotics. The rRNA-modifying enzyme Cfr methylates an adenosine nucleotide within the peptidyl transferase center, resulting in the C-8 methylation of A2503 (m8A2503). Acquisition of cfr results in resistance to eight classes of ribosome-targeting antibiotics. Despite the prevalence of this resistance mechanism, it is poorly understood whether and how bacteria modulate Cfr methylation to adapt to antibiotic pressure. Moreover, direct evidence for how m8A2503 alters antibiotic binding sites within the ribosome is lacking. In this study, we performed directed evolution of Cfr under antibiotic selection to generate Cfr variants that confer increased resistance by enhancing methylation of A2503 in cells. Increased rRNA methylation is achieved by improved expression and stability of Cfr through transcriptional and post-transcriptional mechanisms, which may be exploited by pathogens under antibiotic stress as suggested by natural isolates. Using a variant that achieves near-stoichiometric methylation of rRNA, we determined a 2.2 Å cryo-electron microscopy structure of the Cfr-modified ribosome. Our structure reveals the molecular basis for broad resistance to antibiotics and will inform the design of new antibiotics that overcome resistance mediated by Cfr.

[Display omitted] [ABSTRACT FROM AUTHOR]

ABSTRACTMethylation of the ribosome is a prevalent strategy conferring resistance to antibiotics that inhibit protein synthesis. Methylation is catalyzed by several distinct enzymes, many encoded on mobile genetic elements widespread in bacteria. One enzyme that is increasingly common in Gram-positive pathogens is Cfr. This radical S-adenosyl-L-methionine rRNA methylase confers resistance to the antibiotics phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A (PhLOPSA) via methylation of A2503 of the 23S rRNA of the large ribosomal subunit. One strategy to safeguard the utility of these antibiotics is to identify inhibitors of Cfr-dependent methylation that may rescue antibiotic activity. We screened our in-house library of microbial natural product extracts against Cfr+Escherichia coli and identified an extract from Streptomyces WAC01849 that potentiated the PhLOPSA antibiotic linezolid in a Cfr-dependent manner. We isolated the active angucyclinones 8-O-methyltetrangomycin (MTN) and 8-O-methyltetrangulol (MTL) from this extract. Both compounds selectively potentiated representatives of the PhLOPSA antibiotics in Escherichia coli and methicillin-resistant Staphylococcus aureus in a Cfr-dependent manner. Finally, we observed inhibition of Cfr-mediated ribosome methylation in cells treated with MTN and MTL. Our findings suggest that MTN and MTL interfere with Cfr-dependent methylation to protect the efficacy of the PhLOPSA antibiotics and offer a unique chemical scaffold that may be applied in developing clinically useful Cfr inhibitors.IMPORTANCECfr is an antibiotic resistance enzyme that inhibits five clinically important antibiotic classes, is genetically mobile, and has a minimal fitness cost, making Cfr a serious threat to antibiotic efficacy. The significance of our work is in discovering molecules that inhibit Cfr-dependent methylation of the ribosome, thus protecting the efficacy of the PhLOPSA antibiotics. These molecules are the first reported inhibitors of Cfr-mediated ribosome methylation and, as such, will guide the further discovery of chemical scaffolds against Cfr-mediated antibiotic resistance. Our work acts as a foundation for further development of molecules that safeguard the PhLOPSA antibiotics from Cfr.

Coronary flow reserve (CFR) and microvascular resistance reserve (MRR) can, in principle, be derived by any method assessing coronary flow. The aim of this study was to compare CFR and MRR as derived by continuous (CFR cont and MRR cont) and bolus thermodilution (CFR bolus and MRR bolus). A total of 175 patients with chest pain and nonobstructive coronary artery disease were studied. Bolus and continuous thermodilution measurements were performed in the left anterior descending coronary artery. MRR was calculated as the ratio of CFR to fractional flow reserve and corrected for changes in systemic pressure. In 102 patients, bolus and continuous thermodilution measurements were performed in duplicate to assess test-retest reliability. Mean CFR bolus was higher than CFR cont (3.47 ± 1.42 and 2.67 ± 0.81 [ P < 0.001], mean difference 0.80, upper limit of agreement 3.92, lower limit of agreement −2.32). Mean MRR bolus was also higher than MRR cont (4.40 ± 1.99 and 3.22 ± 1.02 [ P < 0.001], mean difference 1.2, upper limit of agreement 5.08, lower limit of agreement −2.71). The correlation between CFR and MRR values obtained using both methods was significant but weak (CFR, r = 0.28 [95% CI: 0.14-0.41]; MRR, r = 0.26 [95% CI: 0.16-0.39]; P < 0.001 for both). The precision of both CFR and MRR was higher when assessed using continuous thermodilution compared with bolus thermodilution (repeatability coefficients of 0.89 and 2.79 for CFR cont and CFR bolus , respectively, and 1.01 and 3.05 for MRR cont and MRR bolus , respectively). Compared with bolus thermodilution, continuous thermodilution yields lower values of CFR and MRR accompanied by an almost 3-fold reduction of the variability in the measured results. [Display omitted] [ABSTRACT FROM AUTHOR]

The ecology and diversity of resistome in coagulase-negative staphylococci (CoNS) from healthy pigs and pig farmers are rarely available as most studies focused on the livestock-associated methicillin-resistant S. aureus. This study aims to characterize the antimicrobial resistance (AMR) mechanisms, intra-host species diversity (more than one species in a host), and intra-species AMR diversity (same species with more than one AMR profile) in CoNS recovered from the nasal cavities of healthy pigs and pig farmers. One-hundred-and-one CoNS strains previously recovered from 40 pigs and 10 pig farmers from four Spanish pig farms were tested to determine their AMR profiles. Non-repetitive strains were selected (n = 75) and their AMR genes, SCCmec types, and genetic lineages were analyzed by PCR/sequencing. Of the non-repetitive strains, 92% showed a multidrug resistance (MDR) phenotype, and 52% were mecA-positive, which were associated with SCCmec types V (46.2%), IVb (20.5%), and IVc (5.1%). A total of 28% of the pigs and pig farmers had intra-host species diversity, while 26% had intra-species AMR diversity. High repertoires of AMR genes were detected, including unusual ones such as tetO, ermT, erm43, and cfr. Most important was the detection of cfr (in S. saprophyticus and S. epidermidis-ST16) in pigs and pig farmers; whereas MDR-S. borealis strains were identified in pig farmers. Pig-to-pig transmission of CoNS with similar AMR genes and SCCmec types was detected in 42.5% of pigs. The high level of multidrug, within-host, and intra-species resistome diversity in the nasal CoNS highlights their ability to be AMR gene reservoirs in healthy pigs and pig farmers. The detection of MDR-S. borealis and linezolid-resistant strains underscore the need for comprehensive and continuous surveillance of MDR-CoNS at the pig farm level. [ABSTRACT FROM AUTHOR]

IntroductionCoronavirus disease 2019 (COVID-19) has caused more than 690 million deaths worldwide. Different results concerning the death rates of the Delta and Omicron variants have been recorded. We aimed to assess the secular trend of case fatality rate (CFR), identify risk factors associated with mortality following COVID-19 diagnosis, and investigate the risks of mortality and hospitalization during Delta and Omicron waves in the United States.MethodsThis study assessed 2,857,925 individuals diagnosed with COVID-19 in the United States from January 2020, to June 2022. The inclusion criterion was the presence of COVID-19 diagnostic codes in electronic medical record or a positive laboratory test of the SARS-CoV-2. Statistical analysis was bifurcated into two components, longitudinal analysis and comparative analysis. To assess the discrepancies in hospitalization and mortality rates for COVID-19, we identified the prevailing periods for the Delta and Omicron variants.ResultsLongitudinal analysis demonstrated four sharp surges in the number of deaths and CFR. The CFR was persistently higher in males and older age. The CFR of Black and White remained higher than Asians since January 2022. In comparative analysis, the adjusted hazard ratios for all-cause mortality and hospitalization were higher in Delta wave compared to the Omicron wave. Risk of all-cause mortality was found to be greater 14–30 days after a COVID-19 diagnosis, while the likelihood of hospitalization was higher in the first 14 days following a COVID-19 diagnosis in Delta wave compared with Omicron wave. Kaplan–Meier analysis revealed the cumulative probability of mortality was approximately 2-fold on day 30 in Delta than in Omicron cases (log-rank p

Linezolid resistance mediated by the cfr gene in MRSA represents a global concern. We investigated relevant phenotype differences between cfr-positive and -negative MRSA that contribute to pathogenesis, and the efficacy of linezolid-based combination therapies in murine models of bacteremia and skin and skin structure infection (SSSI). As a group, cfr-positive MRSA exhibited significantly reduced susceptibilities to the host defense peptides tPMPs, human neutrophil peptide-1 (hNP-1), and cathelicidin LL-37 (P < 0.01). In addition, increased binding to fibronectin (FN) and endothelial cells paralleled robust biofilm formation in cfr-positive vs. -negative MRSA. In vitro phenotypes of cfr-positive MRSA translated into poor outcomes of linezolid monotherapy in vivo in murine bacteremia and SSSI models. Importantly, rifampicin showed synergistic activity as a combinatorial partner with linezolid, and the EC50 of linezolid decreased 6-fold in the presence of rifampicin. Furthermore, this combination therapy displayed efficacy against cfr-positive MRSA at clinically relevant doses. Altogether, these data suggest that the use of linezolid in combination with rifampicin poses a viable therapeutic alternative for bacteremia and SSSI caused by cfr-positive multidrug resistant MRSA.

Background: Linezolid (Oxazolidinones) is commonly used against a variety of Gram-positive infections, especially methicillin-resistant Staphylococcus aureus (MRSA). The emerging resistance to linezolid curtail the treatment of infections caused by MRSA and other Gram-positive bacteria. Presence of cfr gene plays a crucial role in Linezolid resistance. Objective: Present study was aimed to detect cfr gene among clinical MRSA isolates. Materials and methods: The suspected Staphylococcus aureus isolates were processed through Kirby Bauer disc diffusion methods for the confirmation of MRSA strains. Phenotypic Linezolid resistance was determined through broth micro-dilution method. The plasmid and DNA of Linezolid resistant isolates were subjected to molecular characterization for the presence of cfr gene. Results: Among 100 Staphylococcus aureus isolates, 85 of them were confirmed as MRSA isolates. Categorically, 65% MRSA isolates were sensitive to linezolid with MIC lower than 8 µg/ml, whereas, 35% of them were resistant to linezolid having MIC greater than 8 µg/ml. MIC level of 128 µg/ml was observed among 3.5% of the resistant isolates. Similarly, MIC level of 64 µg/ml, 32 µg/ml, 16 µg/ml and 8 µg/ml were noted for 3.5%, 4.7%, 8.2% and 15.3% isolates respectively. Linezolid resistance cfr gene was detected only in 9.4% of the resistant isolates. Conclusion: Multi drug resistance among MRSA isolates is keenly attributed to the presence of cfr gene as evident in the present study, and horizontal dissemination of cfr gene among MRSA strains is accredited to cfr-carrying transposons and plasmids.

Objectives: Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS). Method: An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated. Results: The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215−4.916) for moderate selenium-deficient counties and 16.002 (14.706−17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061−1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00–8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14–50.16). Conclusion: Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

The cfr genes encode for a 23S rRNA methyltransferase, conferring a multiresistance phenotype to phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A antibiotics. These genes have been described in staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA). In this study, we retrospectively performed an in-depth genomic characterisation of three cfr-positive, multidrug-resistant (MDR) livestock-associated (LA) MRSA clonal complexes (CCs) 1 and 398 detected in different Italian pig holdings (2008–2011) during population studies on Italian livestock (2008–2014). We used a combined Illumina and Oxford Nanopore Technologies (ONT) whole genome sequencing (WGS) approach on two isolates (the 2008 CC1 and the 2010 CC398 isolates, but not the 2011 CC1 isolate). Interestingly, the three isolates presented different cfr variants, with only one displaying a linezolid-resistant phenotype. In isolate 2008 CC1, the cfr gene was identified within a Tn558 composite transposon-like structure flanked by IS elements located on a novel 44,826 bp plasmid. This represents the first report of CC1 LA-MRSA harbouring the cfr gene in its functional variant. Differently, cfr was chromosomally located in isolate 2010 CC398. Our findings have significant public health implications, confirm the need for the continuous genomic surveillance of cfr-positive zoonotic LA-MRSA, and backdate cfr presence in LA-MRSA from Italian pigs to at least 2008. [ABSTRACT FROM AUTHOR]

BackgroundSymptoms suggestive of myocardial ischemia are frequently encountered in patients with atrial fibrillation (AF) even in the absence of obstructive coronary artery disease. Nevertheless, an in-depth characterisation of coronary physiology in patients with AF is currently lacking.ObjectivesWe aim to provide an insight into the characteristics of coronary physiology in AF, by performing simultaneous invasive measurements of coronary flow- and pressure- indices in a real-life population of patients with AF and indication of coronary angiography.MethodsThis is a prospective open label study including patients with permanent or persistent AF and indication of coronary angiography showing intermediate coronary stenosis requiring routine physiological assessment (n = 18 vessels from 14 patients). We measured FFR (fractional flow reserve), and Doppler-derived coronary flow indices, including CFR (coronary flow reserve) and HMR (hyperaemic microvascular resistance).ResultsFrom the analysed vessels, 18/18 vessels (100%) presented a pathological CFR (

Objects: Variants of Severe-Acute-Respiratory-Syndrome Coronavirus-2 (SARS-CoV-2) has caused tremendous impact globally. It has been widely reported that the Omicron (B.1.1.529) variant is less deadly than the Delta (B.1.617.2) variant, presumably due to immunity from vaccination and previous infection. When measuring the severity of a variant, Case-Fatality-Rate (CFR) is often estimated. The purpose of this work is to calculate the change in CFR of different variants over time from a large number of countries/regions since the start of the pandemic in 2020. Study design: A Cross-sectional study. Methods: We extend the comparison to all previous VOCs in 58 counties/regions. We use reported death divided by reported cases in 30-day sliding window with a two-week shift between reported death and reported cases. Results: The drop from Delta variant to Omicron variant is substantial and the difference between subvariants of Omicron is not evident. Conclusion: We showed that the CFR dropped over time, presumably due to vaccine-induced immune and infection induced immune. Population age structure and prevalence of comorbidity influence CFR.

Linezolid resistance mediated by the cfr gene in MRSA represents a global concern. We investigated relevant phenotype differences between cfr-positive and -negative MRSA that contribute to pathogenesis, and the efficacy of linezolid-based combination therapies in murine models of bacteremia and skin and skin structure infection (SSSI). As a group, cfr-positive MRSA exhibited significantly reduced susceptibilities to the host defense peptides tPMPs, human neutrophil peptide-1 (hNP-1), and cathelicidin LL-37 (P < 0.01). In addition, increased binding to fibronectin (FN) and endothelial cells paralleled robust biofilm formation in cfr-positive vs. -negative MRSA. In vitro phenotypes of cfr-positive MRSA translated into poor outcomes of linezolid monotherapy in vivo in murine bacteremia and SSSI models. Importantly, rifampicin showed synergistic activity as a combinatorial partner with linezolid, and the EC50 of linezolid decreased 6-fold in the presence of rifampicin. Furthermore, this combination therapy displayed efficacy against cfr-positive MRSA at clinically relevant doses. Altogether, these data suggest that the use of linezolid in combination with rifampicin poses a viable therapeutic alternative for bacteremia and SSSI caused by cfr-positive multidrug resistant MRSA.

Escherichia coli is a Gram-negative Bacilli belonging to the Enterobacteriaceae family. It has a rod-shaped coliform . A number of neuropsychiatric conditions, likeanxiety, schizophrenia, autism, bipolar disorder, and depressive disorder, Have been reported to be associated with the microbiome. Autism spectrum disorder (ASD), is a neurodevelopmental disturbance. A sample of fifteen E.coli bacteria were isolated E. coliisolates From ASD children's stools.ASD children. The isolates were identified by phenotypic identification using API 20 E. The molecular analysis was processed for Integron I,II,I, cfr, procfr genes.These resultsshowed Integron II less prevalence Than in IntegronIand III. I,III while pro-cfr, more prevalence than cfrgene.Multidrug-resistant in E. coli has widespread.

Positron Emission Tomography (PET) Myocardial Perfusion Imaging (MPI) is a robust diagnostic and prognostic test in patients with suspected or known coronary artery disease (CAD). We aimed to assess the incremental prognostic value of myocardial flow reserve (MFR) using the latest generation of digital PET scanners. Consecutive patients with clinically indicated PET MPI for suspected or known CAD were included. Myocardial blood flow (MBF) in ml/min/g was obtained from dynamic images at rest and peak hyperemia, and the myocardial flow reserve (MFR) was calculated as the ratio of stress to rest MBF. Patients were followed from the date of PET imaging for the occurrence of the primary outcome (composite of all-cause death, myocardial infarction, and Percutaneous Coronary Intervention or Coronary Artery Bypass Graft occurring >90 days after imaging). Nested multivariable Cox regression models were used to assess the incremental prognostic role of MFR over traditional risk factors and PET relative perfusion parameters. The final cohort consisted of 3534 patients (mean age 67 ± 12 years, 48% female, 67% Caucasian, 53% obese, 55% hypertension, 32% diabetes, 42% dyslipidemia). During a median follow-up of 8.5 (3.0–15.4) months, 229 patients (6.5%, 6.4 per 1000 person-years) experienced the primary outcome. In nested multivariable Cox models, impaired MFR (MFR < 2) was significantly associated with the primary outcome (HR 2.9, 95% CI 2.0–4.1, p < 0.001) and significantly improved discrimination (Harrell's C 0.77, p = 0.002). MFR derived from digital PET scanners has an independent and incremental prognostic role in patients with suspected or known CAD. • PET MPI is a robust diagnostic and prognostic test for managing patients with suspected or established CAD. • Digital PET MPI has higher sensitivity at a lower radiotracer dose, radiation exposure (below 1milisilvert), and cost. • We aimed to assess the incremental prognostic value of MFR using the latest generation of digital PET scanners. • We found digital PET MFR has an independent and incremental prognostic role in patients with suspected or known CAD. [ABSTRACT FROM AUTHOR]

Objectives: Coronary flow reserve (CFR) is a strong predictor of cardiovascular events and prognosis in patients with coronary artery disease. This study aimed to evaluate preoperative factors associated with the unsuccessful restoration of CFR after coronary artery bypass grafting (CABG). Methods : Included in this study were the 65 patients who presented with functionally significant left anterior descending artery (LAD) lesions confirmed by both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR), and who underwent successful CABG at our hospital within the study period. After CABG, graft patency was confirmed by coronary computed tomography angiography, and CFR in the LAD artery was measured by echocardiography. We defined postoperative CFR <2.5 as impaired CFR, and CFR ≥2.5 as preserved CFR. Results: Of the 65 patients, 14 patients (22%) showed impaired CFR, while 51 patients had preserved CFR. Patients with impaired CFR had significantly higher HbA1c (6.7% vs. 6.0%, P < 0.01), greater use of insulin (43% vs. 4%, P < 0.01), longer lesion length (33 mm vs. 25 mm, P = 0.044), and lower iFR (0.69 vs 0.81, P = 0.01) than those with preserved CFR, although both groups had comparable FFR (0.65 vs 0.64, P = 0.46). In receiver operating characteristic curve analysis, iFR had a significantly larger area under the curve than FFR in terms of the prediction of impaired CFR (0.74 vs 0.42, P = 0.01). Conclusions: Poorly-controlled preoperative diabetes, greater reliance on insulin, longer lesion length and lower iFR were associated with postoperative impaired CFR, suggesting the involvement of microvascular dysfunction. [Display omitted] • Coronary flow reserve (CFR) has been proposed as a powerful prognostic predictor. • CABG is basically an established treatment to improve CFR and prognosis. • There has been the cases of continued impairment of CFR after successful CABG. • Diabetes and longer lesion are the risk factors for continued impairment of CFR. • iFR was more predictive of postoperative CFR than FFR. [ABSTRACT FROM AUTHOR]

The ecology and diversity of resistome in coagulase-negative staphylococci (CoNS) from healthy pigs and pig farmers are rarely available as most studies focused on the livestock-associated methicillin-resistant S. aureus. This study aims to characterize the antimicrobial resistance (AMR) mechanisms, intra-host species diversity (more than one species in a host), and intra-species AMR diversity (same species with more than one AMR profile) in CoNS recovered from the nasal cavities of healthy pigs and pig farmers. One-hundred-and-one CoNS strains previously recovered from 40 pigs and 10 pig farmers from four Spanish pig farms were tested to determine their AMR profiles. Non-repetitive strains were selected (n = 75) and their AMR genes, SCCmec types, and genetic lineages were analyzed by PCR/sequencing. Of the non-repetitive strains, 92% showed a multidrug resistance (MDR) phenotype, and 52% were mecA-positive, which were associated with SCCmec types V (46.2%), IVb (20.5%), and IVc (5.1%). A total of 28% of the pigs and pig farmers had intra-host species diversity, while 26% had intra-species AMR diversity. High repertoires of AMR genes were detected, including unusual ones such as tetO, ermT, erm43, and cfr. Most important was the detection of cfr (in S. saprophyticus and S. epidermidis-ST16) in pigs and pig farmers; whereas MDR-S. borealis strains were identified in pig farmers. Pig-to-pig transmission of CoNS with similar AMR genes and SCCmec types was detected in 42.5% of pigs. The high level of multidrug, within-host, and intra-species resistome diversity in the nasal CoNS highlights their ability to be AMR gene reservoirs in healthy pigs and pig farmers. The detection of MDR-S. borealis and linezolid-resistant strains underscore the need for comprehensive and continuous surveillance of MDR-CoNS at the pig farm level.

ABSTRACT The multidrug resistance gene cfr mediates resistance to multiple antimicrobial agents, including linezolid. Plasmids are the preferred vector for the dissemination of cfr. However, the presence and transmission of cfr-carrying plasmids among staphylococci from humans and animals have rarely been studied. Here, we investigated the presence of the cfr gene in 2,250 staphylococci of human clinical origin collected in Zhejiang, China, in 1998 to 2021 and in 3,329 porcine staphylococci preserved in our laboratories. The cfr gene was detected in 38 human isolates; its presence in Staphylococcus haemolyticus and Staphylococcus cohnii in 2003 was earlier than that identified in 2005, and Staphylococcus capitis (n = 30) was the predominant species. The cfr-carrying fragment in 38 isolates exhibited >99% nucleotide sequence similarity to plasmid pLRSA417 (39,504 bp), which was identified in 2015 and originated from a human clinical methicillin-resistant Staphylococcus aureus isolate from Zhejiang, China. The cfr-carrying plasmids in 18 MinION-sequenced staphylococci ranged in size from 32,697 bp to 43,457 bp. Fifteen plasmids were identical to pLRSA417, except for the inversion of an 8.4-kb segment comprising IS256-aacA/aphD-ISEnfa4_1-cfr-ISEnfa4_2, while the remaining 3 plasmids exhibited slightly different structures. Among the 114 cfr-positive staphylococci from pigs, pLRSA417-like plasmids were detected in 3 isolates. Intraspecies and interspecies conjugation occurred in human-derived pLRSA417-like plasmids. The presence of pLRSA417-like plasmids in staphylococci from multiple geographic regions and different hosts implied the possible transmission of the respective isolates between humans and animals. IMPORTANCE The therapeutic efficacy of the oxazolidinone antimicrobial linezolid is reduced by the emergence and dissemination of the multidrug resistance gene cfr. The cfr-carrying plasmid pLRSA417 was first identified in a clinical methicillin-resistant Staphylococcus aureus isolate, but its presence in staphylococci of human and animal origin has not been reported previously. This study showed that conjugative plasmids similar to pLRSA417 were detected mainly in Staphylococcus capitis and existed in different staphylococci in 2003 to 2021 in various clinical departments in the same hospital. pLRSA417-like plasmids were also present in staphylococci of food animal sources from different geographic regions, which suggested possible transmission among humans and animals.

Linezolid (Oxazolidinones) is commonly used against a variety of Gram-positive infections, especially methicillin-resistant Staphylococcus aureus (MRSA). The emerging resistance to linezolid curtail the treatment of infections caused by MRSA and other Gram-positive bacteria. Presence of cfr gene plays a crucial role in Linezolid resistance. Present study was aimed to detect cfr gene among clinical MRSA isolates. The suspected Staphylococcus aureus isolates were processed through Kirby Bauer disc diffusion methods for the confirmation of MRSA strains. Phenotypic Linezolid resistance was determined through broth micro-dilution method. The plasmid and DNA of Linezolid resistant isolates were subjected to molecular characterization for the presence of cfr gene. Among 100 Staphylococcus aureus isolates, 85 of them were confirmed as MRSA isolates. Categorically, 65% MRSA isolates were sensitive to linezolid with MIC lower than 8 µg/ml, whereas, 35% of them were resistant to linezolid having MIC greater than 8 µg/ml. MIC level of 128 µg/ml was observed among 3.5% of the resistant isolates. Similarly, MIC level of 64 µg/ml, 32 µg/ml, 16 µg/ml and 8 µg/ml were noted for 3.5%, 4.7%, 8.2% and 15.3% isolates respectively. Linezolid resistance cfr gene was detected only in 9.4% of the resistant isolates. Multi drug resistance among MRSA isolates is keenly attributed to the presence of cfr gene as evident in the present study, and horizontal dissemination of cfr gene among MRSA strains is accredited to cfr -carrying transposons and plasmids. [ABSTRACT FROM AUTHOR]

Objectives: To determine the case-fatality rate (CFR) of coronavirus disease 2019 (Covid-19) and its associated determinants in order to understand the true magnitude of the problem during the ongoing conflict in Yemen. Methods: The CFR among the confirmed Covid-19 cases in Yemen was calculated. The data was retrieved from national Covid-19 surveillance between April 10, when the first COVID-19 case reported, and May 31, 2020. Results: A total of 419 confirmed Covid-19 cases were reported. There were 14.1% and 5.7% of cases who required intensive care and mechanical ventilators, respectively. Out of the total cases, 95 deaths were reported, giving a CFR of 22.6% which is much higher compared to other countries. CFR was significantly higher among elderly people compared to young adults and varied between governorates. Mortality was associated with pre-existing hypertension (OR: 2.30; 95% CI: 1.58, 3.54) and diabetes (OR: 1.68; 95% CI: 1.08, 2.61). Conclusions: The elderly and those with comorbidities, in particular hypertension and diabetes, have higher risk for poor outcomes and therefore should receive more attention in the clinical setting. Preventive measures should also be prioritized to protect those groups in order to reduce the severe cases and deaths-associated COVID-19 in armed-conflict. [ABSTRACT FROM AUTHOR]

Background: Ischemia and no obstructive coronary artery disease (INOCA) patients who presented coronary microvascular dysfunction (CMD) demonstrate a poor prognosis, yet the risk factors for CMD remain unclear. Subtle changes in thyroid hormone levels within the normal range, especially the free thyroxine (FT4)/free triiodothyronine (FT3) ratio, have been shown to regulate the cardiovascular system. This prospective study investigated the correlation between FT4/FT3 ratio and CMD in euthyroid patients with INOCA. Methods: This prospective study (www.chictr.org.cn/, ChiCTR2000037112) recruited patients with myocardial ischemia symptoms who underwent both coronary angiography (CAG) and myocardial perfusion imaging (MPI) with dynamic single-photon emission computed tomography (D-SPECT). INOCA was defined as coronary stenosis< 50% and CMD was defined as coronary flow reserve (CFR)<2.5. All patients were excluded from abnormal thyroid function and thyroid disease history. Results: Among 71 INOCA patients (15 [21.1%] CMD), FT4 and FT4/FT3 ratio in CMD group were significantly higher and both showed significantly moderate correlation with CFR (r=-0.25, p=0.03; r=-0.34, p=0.003, respectively). The ROC curve revealed that FT4/FT3 ratio had the highest efficacy for predicting CMD with an optimized cutoff value>3.39 (AUC 0.78, p<0.001, sensitivity, 80.0%; specificity, 71.4%). Multivariate logistic regression showed that FT4/ FT3 ratio was an independent predictor of CMD (OR 7.62, 95% CI 1.12-51.89, p=0.038, P for trend=0.006). Conclusion: In euthyroid INOCA patients, increased FT4/FT3 ratio levels are associated with the occurrence of CMD, presenting a novel biomarker for improving the risk stratification. [ABSTRACT FROM AUTHOR]

The plasmid-borne cfr gene, mediating multiple drug resistance (MDR), has been observed in many Gram-positive bacteria. The prevalence of cfr and its co-occurrence with additional antimicrobial resistance (AMR) determinants in Escherichia coli is an ongoing issue. Additionally, the prevalence and transfer mechanism of the cfr gene remain partially investigated. Here, eight cfrpositive E. coli strains were screened using PCR from an extensive collection of E. coli (n = 2,165) strains isolated from pigs and chickens in 2021 in China, with a prevalence rate of 0.37%. All of them were MDR and resistant to florfenicol and tetracycline. These strains can transfer the cfr gene to E. coli J53 by conjugation (1.05 × 10-1 - 1.01 × 10-6). Moreover, the IncX4 plasmid p727A3-62 K-cfr (62,717 bp) harboring cfr in strain EC727A3 was confirmed using Oxford Nanopore Technology. The unknown type plasmid p737A1-27Kcfr (27,742 bp) harboring cfr in strain EC737A1 was also identified. Notably, it was verified by PCR that three of the eight E. coli strains were able to form the cfr-IS26 circular intermediate. It was 2,365 bp in length in strains EC727A3 and ECJHZ21-173, and 2,022 bp in length in EC737A1. Collectively, this study demonstrated that IS26 plays a vital role in transmitting the MDR gene cfr in E. coli via conjugation and provided updated knowledge regarding cfr in E. coli in Eastern China. [ABSTRACT FROM AUTHOR]

• There is a higher incidence of severe fever with thrombocytopenia syndrome (SFTS) in selenium-deficient areas. • Mortality of SFTS is higher in severe selenium-deficient areas. • Insufficient serum selenium in humans is associated with poor prognosis in SFTS. Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS). An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated. The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215−4.916) for moderate selenium-deficient counties and 16.002 (14.706−17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061−1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00–8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14–50.16). Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes. This is special type of abstract that is so short and could be inserted after main abstract of article, as a blurb or inserted as annotations into a Table of contents [Display omitted] [ABSTRACT FROM AUTHOR]

Using eight cross-section econometric models applied to a sample of 31 countries, we find that, although the Case Fatality Ratio (CFR) of COVID-19 is explained by 'structural' variables that were given prior to the pandemic (healthcare infrastructure, comorbidities, poverty and the HDI), the 'response' variables to the crisis (fiscal support, health policy, and, above all, government narrative) have been determinant in the evolution of the pandemic. We show that the dummy variable representing populist countries is significant, demonstrating that, as Shiller (2017) stated, narrative plays a major role in shaping behavior and economic outcomes. [ABSTRACT FROM AUTHOR]

A lot of people with coronary artery disease do not have specific symptoms, and myocardial infarction or death are the first manifestation of the disease. New accurate, non-invasive and safe screening methods are required that can assess the prognosis of patients during routine examinations performed on millions of people. The aim of this review was to discuss the current literature regarding the utility of non-invasive ultrasound imaging of the coronary artery in assessing a patient's prognosis in daily practice. Assessment of coronary artery flow during common stress echocardiography or echocardiography can provide additive incremental prognostic information without the burden of radiation. Exercise or pharmacologic stress echocardiography tests combined with coronary flow velocity reserve assessment has advantages over stress tests based only on regional wall motion abnormalities. Scanning of main coronary arteries as an addition to routine echocardiography can reveal patients at high risk of adverse cardiac events in the near future. [ABSTRACT FROM AUTHOR]