Tango-seq: overlaying transcriptomics on connectomics to identify neurons downstream of Drosophila clock neurons.

Knowing how neural circuits change with neuronal plasticity and differ between individuals is important to fully understand behavior. Connectomes are typically assembled using electron microscopy, but this is low throughput and impractical for analyzing plasticity or mutations. Here, we modified the trans-Tango genetic circuit-tracing technique to identify neurons synaptically downstream of Drosophila s-LNv clock neurons, which show 24hr plasticity rhythms. s-LNv target neurons were labeled specifically in adult flies using a nuclear reporter gene, which facilitated their purification and then single cell sequencing. We call this Tango-seq, and it allows transcriptomic data - and thus cell identity - to be overlayed on top of anatomical data. We found that s-LNvs preferentially make synaptic connections with a subset of the CNMa+ DN1p clock neurons, and that these are likely plastic connections. We also identified synaptic connections between s-LNvs and mushroom body Kenyon cells. Tango-seq should be a useful addition to the connectomics toolkit.

Perceived barriers and factors influencing uptake of breast cancer screening among women: a population-based cross-sectional study.

Breast cancer (BC) screening plays a major role in the prevention of BC through early detection and timely treatment. This study aims to determine the level of uptake of BC screening and associated factors. A community-based analytical cross-sectional study was conducted in Dodoma City, Tanzania from July to December 2020. The study included women aged 8 years and above without a known history of breast cancer. Multivariable logistic regression was used to determine the socio-demographic factors associated with BC screening. P value < 0.05 was considered significant. A total of 354 study participants were included in the present study. The mean age of participants was 31.0 ± 11.8 years. The majority of study participants (67.5%, n = 239) were aware of BC screening. However, only (35.3%, n = 125) reported to have ever practised BC screening. Breast self-examination was the most (16.4%, n = 58) frequently used method for BC screening among study participants. Lack of knowledge of all methods of BC screening was the barrier that was perceived by the vast majority (60.2%, n = 213) of the study participants. Having low family income was the only predictor of failure to practice BC screening. In this study, most of the women were aware of BC, however, few of them had undergone breast cancer (BC) screening at the time of the interview. The study also found that the main barrier to BC screening was the lack of knowledge about BC among the study participants. Immediate measures are necessary to increase women's awareness of BC. Such as community sensitization on the importance of screening, can help improve the uptake of BC screening and the early detection of BC.

Miyoshi myopathy associated with spine rigidity and multiple contractures: a case report.

BACKGROUND: Dysferlinopathy is a phenotypically heterogeneous group of hereditary diseases caused by mutations in the DYSF gene. Early contractures are considered rare, and rigid spine syndrome in dysferlinopathy has been previously reported only once. CASE PRESENTATION: We describe a 23-year-old patient with Miyoshi myopathy with a rigid spine and multiple contractures, a rare phenotypic variant. The disease first manifested when the patient was 13 years old, with fatigue of the gastrocnemius muscles and the development of pronounced contractures of the Achilles tendons, flexors of the fingers, and extensors of the toes, followed by the involvement of large joints and the spine. Magnetic resonance imaging revealed signs of connective tissue and fatty replacement of the posterior muscles of the thighs and lower legs. Edema was noted in the anterior and medial muscle groups of the thighs, lower legs, and the multifidus muscle of the back. Whole genome sequencing revealed previously described mutations in the DYSF gene in exon 39 (c.4282 C > T) and intron 51 (c.5785-824 C > T). An immunohistochemical analysis and Western blot showed the complete absence of dysferlin protein expression in the muscle fibers. CONCLUSIONS: This case expands the range of clinical and phenotypic correlations of dysferlinopathy and complements the diagnostic search for spine rigidity.

Intimate partner violence influences modern family planning use among married women in Tanzania: cross-sectional study.

BACKGROUND: Married women who experience intimate partner violence (IPV) are less likely to negotiate with their partners on modern family planning (FP) use. This study aimed to determine the influence of intimate partner violence and sociodemographics on modern family planning use. METHODS: A community-based cross-sectional study was conducted in the Mara region, Tanzania from April to July 2020. A total of 366 married women were interviewed. Data were collected using a structured interviewer-administered questionnaire. Analysis was done using SPSS version 25, and a binary logistic regression model was used to determine the predictors of modern FP use. The significance level was set at a p-value less than 0.05. RESULTS: The overall prevalence of IPV was 73% with 54.1% physical, 36.3% psychological, and 25.4%, sexual violence. The prevalence of modern FP use was 62%, and the most (49.1%) common method practiced by married women was injection (Depo Provera). Physical violence (AOR = 0.32, p = 0.0056), and psychological violence (AOR = 0.22, p = 0.0022) had significantly reduced odds of modern FP use. Religion (AOR = 4.6, p = 0.0085), and availability of preferred modern FP methods (AOR = 9.27, p < 0.0001) had significantly increased odds of modern FP use. CONCLUSION: In this study, there is a positive association between the use of modern FP methods and IPV. To prevent IPV and its negative health consequences, it is crucial to involve community leaders and primary healthcare workers. They can help in identifying the best strategies to prevent IPV and promote the use of modern FP methods. It is equally important to involve male partners in reproductive health decisions, including the use of modern FP methods. This approach will help reduce reproductive coercion.

"We always felt psychologically unstable": A qualitative study of midwives' experiences in providing maternity care during the COVID-19 pandemic in Tanzania.

AIM: We explored midwives' experiences and challenges in providing maternity care during the period of the first surge of the COVID-19 pandemic in Dodoma. DESIGN: Phenomenological study design was used to explore midwives' experiences and challenges in providing maternity care during the COVID-19 pandemic in Tanzania. METHODS: We conducted interviews with a total of 23 midwives, using semi-structured interviews and an audio recorder. Five focus group discussions (FGDs) were conducted. To analyse the data, we used interpretive phenomenological thematic data analysis with NVivo software. To analyse templates, we followed a step-by-step process, starting with familiarizing ourselves with the data, followed by preliminary coding, organizing themes, developing an initial coding template, using the initial template, refining the template and finally applying it to the entire dataset. RESULTS: It was found that three themes and eight subthemes merged in the current study. The main themes were ① mental health distress, ② work environment challenges and ③ isolation of midwives by different groups. PUBLIC CONTRIBUTION: Reducing risk and protecting midwives from infectious diseases will improve the workforce, reduce the number of hospital stays, reduce the cost of hospital services, improve birth outcomes and indirectly improve family, community and national economies. CONCLUSION: Due to the system's failure to provide psychological support, protective environment and isolation rooms for confirmed or suspected cases put midwives at a higher risk of contracting the virus and had to work in a stressful environment. In addition to having the right tools, midwives must also receive emotional and psychological support in order to be at their best. The system must ensure that midwives are ready for uncertain times, such as pandemic infectious disease outbreaks, by providing protective work place environment such as personal protective equipment, psychological support and isolation room for confirmed COVID-19 cases.

Treatment of Metastatic Renal Cell Carcinoma with Checkpoint Inhibitors in Clinical Practice in the Volga-Ural Region of the Eurasian Continent.

INTRODUCTION: Renal cancer ranks 10th in the mortality structure of the Russian Federation. The introduction of checkpoint inhibitors has changed the paradigm of treatment of patients with malignant neoplasms. METHOD: Data from clinical trials have shown good progression-free median and median overall survival. Each cancer center has been accumulating its own experience in treating patients with renal cell cancer by applying modern target drugs and immunotherapy. RESULT: In routine clinical practice, oncologists do not get the results that have been demonstrated in clinical trials when evaluating the effectiveness of the therapy. CONCLUSION: In this single-center clinical study, we discuss the results of using nivolumab as mono-therapy and the combination of nivolumab with ipilimumab in metastatic renal parenchyma cancer patients.

Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch in C. elegans.

A growing body of evidence suggests that cell division and basement membrane invasion are mutually exclusive cellular behaviors. How cells switch between proliferative and invasive states is not well understood. Here, we investigated this dichotomy in vivo by examining two cell types in the developing Caenorhabditis elegans somatic gonad that derive from equipotent progenitors, but exhibit distinct cell behaviors: the post-mitotic, invasive anchor cell and the neighboring proliferative, non-invasive ventral uterine (VU) cells. We show that the fates of these cells post-specification are more plastic than previously appreciated and that levels of NHR-67 are important for discriminating between invasive and proliferative behavior. Transcription of NHR-67 is downregulated following post-translational degradation of its direct upstream regulator, HLH-2 (E/Daughterless) in VU cells. In the nuclei of VU cells, residual NHR-67 protein is compartmentalized into discrete punctae that are dynamic over the cell cycle and exhibit liquid-like properties. By screening for proteins that colocalize with NHR-67 punctae, we identified new regulators of uterine cell fate maintenance: homologs of the transcriptional co-repressor Groucho (UNC-37 and LSY-22), as well as the TCF/LEF homolog POP-1. We propose a model in which the association of NHR-67 with the Groucho/TCF complex suppresses the default invasive state in non-invasive cells, which complements transcriptional regulation to add robustness to the proliferative-invasive cellular switch in vivo.

Determinants of knowledge, attitude, and practice among patients with type 2 diabetes mellitus: A cross-sectional multicenter study in Tanzania.

Improvement of primary care for patients with type 2 diabetes mellitus (T2DM) through the promotion of good knowledge, attitude, and practice is of paramount importance for preventing its related complications. This study aimed to assess the levels of knowledge, attitude, and practice and associated factors among patients with T2DM. This was a cross-sectional multicenter hospital-based study that included 979 patients from 8 health facilities in Tanzania. A standardized semi-structured interviewer-administered questionnaire was used to extract the required data. Factor analysis was used to determine the level of knowledge, attitude, and practice. Multivariable analysis under binary logistic regression analysis was used to determine the predictors of knowledge, attitude, and practice. P<0.05 was considered significant. The levels of adequate knowledge, positive attitude, and appropriate practice were 62.1%, 54%, and 30.9%, respectively. Being self-employed (AOR = 1.74, 95% CI = 0.28-0.91, p = 0.040) predicted adequate knowledge. Being male (AOR = 1.46, 95% CI = 1.06-2.01, p = 0.021 and visiting regional hospitals (AOR = 2.17, 95% CI = 1.33-2.51, p = 0.013) were predictors of positive attitude. Residing in rural areas and not having adequate knowledge of diabetes were less likely associated with appropriate practice. This study has shown a significantly low level of appropriate practice among patients with T2DM towards general issues on diabetes, risk factors, and related complications. Therefore, emphasis should be placed on improving good practices that can help prevent related complications.

Coccidioides spp. exposure among military working dogs in endemic regions of the United States.

Coccidioidomycosis is a fungal disease in arid regions of the United States that is predicted to expand with climate change. Cases in military personnel and military working dogs (MWDs) impact personnel readiness and result in healthcare costs. To examine Coccidioides exposure among MWDs, 276 banked serum samples were retrieved from dogs housed in California, Texas, Arizona, New Mexico, Nevada, and Utah. Using gel immunodiffusion, six (2.1%) specimens were IgG-positive and three (1.1%) were equivocally IgM-positive. The IgG-positive samples were from Arizona (2 [prevalence 8.0%]) and California (4 [3.7%]). These data will guide future efforts to study MWDs as sentinels for human coccidioidomycosis.

This study aimed to determine the prevalence of exposure to coccidioidomycosis, the cause of Valley Fever in both humans and animals, among military working dogs (MWDs)located in endemic regions of the United States. The data will be used to guide efforts to study MWDs as sentinels for human disease.

The effect of low-fidelity simulation training on breastfeeding knowledge, practice, and self-efficacy among young lactating mothers in Tanzania: A quasi-experimental study.

BACKGROUND: Exclusive breastfeeding (EBF) is of paramount importance for the survival, growth, and development of neonates. Lack of EBF puts mothers and their babies at high risk of many complications. Mothers may end up having breast engorgement, cracked nipple, mastitis, breast pain, and backache. Babies may acquire postnatal HIV transmission, reduce weight, stunting, poor cognitive and motor development, and increase the risk of diarrhea disease and respiratory infection. Breastfeeding training has been provided immediately after a women's birth. However, young mothers are still staggering with breastfeeding. RESEARCH AIM: We aim to assess the effect of low-fidelity simulation training on breastfeeding knowledge, practice, and self-efficacy among young lactating mothers and we will also assess the impact of simulation on infants' weight in Tanzania. METHODS: The study will be a health facility-based quasi-experimental design. The study will have four phases: baseline survey, intervention, immediate assessment, and two-month end-line follow-up. The assessment will focus on participants' breastfeeding knowledge, practice, and self-efficacy. Furthermore, infant weight will also be assessed during baseline and end-line. A total of 261 young lactating mothers who have first baby with their infants aged 0 to 2 months will be included, whereby 87 young lactating mothers will be in an interventional group and 174 will be in the control group. The intervention will have four packages: 1) group lecture education and interactive on the importance of breastfeeding 2) videos, 3) pictures, and 4) simulation in the umbrella LVPS using the wearable Lactation Simulation Model (LSM) and newborn manikins (Global Health Media and Laerdal baby). At the end of the study, all groups will be given education brochures which will be in the Swahili language for easy understanding. Data will be analyzed using SPSS version 23. An independent T-test and repeated measures ANOVA will be used in this study to compare the difference between the mean of the 2 groups. DISCUSSION: This study aims to generate evidence of the effect of simulation on improving breastfeeding knowledge, practice, and self-efficacy. We expect the study findings to inform the stakeholders and policymakers on formulating breastfeeding education and simulation training that will improve women's breastfeeding knowledge, practice, and self-efficacy and improve infant health.

Contribution of Health Care Practitioner and Maternity Services Factors to Racial Disparities in Alabama: A Qualitative Study.

OBJECTIVE: Black patients are three times more likely to die of pregnancy-related causes than White patients in the United States, and Alabama has the third worst maternal mortality rate in the nation. We sought to identify health care practitioner and maternity service factors contributing to disparities in Alabama, as well as potential strategies to address these contributors. METHODS: We conducted key informant interviews with obstetricians, nurses, doulas, lactation counselors, health system administrators, and representatives of professional organizations who deliver maternity care to racially and ethnically diverse patients in Alabama. The interview guide was developed using Howell's conceptual framework on racial and ethnic disparities in severe maternal morbidity and mortality. Adopting a thematic analysis approach, we coded and analyzed transcripts using NVivo 12 software. Open coding and selective coding were conducted to identify themes related to health care practitioner- and maternity services-level determinants. RESULTS: Overall, 20 health care practitioners or administrators were interviewed. Primary themes related to health care practitioners included implicit bias and explicit racism, lack of communication and lack of positive patient-health care practitioner relationships, lack of cultural sensitivity, and variation in clinical knowledge and experience. Primary themes related to maternity services included lack of accessibility, inadequate quality and content of care, lack of continuity of care, discriminatory facility policies, and workforce shortages and lack of diversity. Strategies suggested by participants to address these factors included bias trainings for health care practitioners, improvements in racial and interdisciplinary diversity in the maternity workforce, and evidence-based interventions such as group prenatal care, disparities dashboards, simulation trainings, early warning signs criteria, and coordinated care. CONCLUSION: We gained diverse perspectives from health care practitioners and administrators on how maternity health care practitioner and maternity health services factors contribute to inequities in maternal health in Alabama. Strategies to address these contributing factors were multifaceted.

Community and Systems Contributors and Strategies to Reduce Racial Inequities in Maternal Health in the Deep South: Provider Perspectives.

Purpose: Black pregnant individuals in Alabama are disproportionately affected by severe maternal morbidity and mortality (SMM). To understand why racial disparities in maternal health outcomes persist and identify potential strategies to reduce these inequities, we sought perspectives from obstetric health care providers, health administrators, and members of local organizations who provide pregnancy, delivery, and postpartum care services in Alabama. Methods: We conducted qualitative in-depth interviews with stakeholders (n=20), purposively recruited from community-based organizations, clinical settings, government organizations, and academic institutions. Interview guides were based on Howell's conceptual model of pathways to racial disparities in maternal mortality. Data were coded using a modified framework theory approach and analyzed thematically. Results: Racism, unjust laws and policies, and poverty/lack of infrastructure in communities emerged as major themes contributing to racial disparities in maternal health at the community and systems levels. Inadequate health insurance coverage was described as a strong driver of the disparities. Service providers suggested strategies for Alabama should be community focused, evidence based, and culturally sensitive. These should include Medicaid expansion, expanded parental leave, and removal of laws restricting choice. Community- and systems-level interventions should include community infrastructure improvements, choice in maternity services, and provision of digital communication options. Conclusions: Providers shared perspectives on community and structural areas of intervention to reduce racial inequities in SMM. These results can inform discussions with health system and community partners about Alabama and other Deep South initiatives to improve maternal health outcomes in black communities.

Synthesis of Charge-Compensated nido-Carboranyl Derivatives of Sulfur-Containing Amino Acids and Biotin.

A new group of charge-compensated nido-carboranyl derivatives of sulfur-containing amino acids and biotin has been synthesized in which the boron atom in position 9 or 10 of carborane is attached to a positively charged sulfur atom. The possibilities of obtaining symmetrical B(10)-substituted and asymmetric B(9)-substituted nido-carboranes were studied. Using the example of (S)-methionine and D-biotin derivatives, water-soluble S-substituted charge-compensated nido-carboranes with free functional groups were prepared. The results obtained open up prospects for the development of potential boron delivery agents for BNCT as well as new bioactive compounds containing a negatively charged nido-carboranyl fragment bearing a positive charge on the sulfur atom associated with the boron cluster.

Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Causing Nosocomial Meningitis in the Neurological Intensive Care Unit.

Acinetobacter baumannii is one of the significant healthcare-associated meningitis agents characterized by multidrug resistance and a high mortality risk. Thirty-seven A. baumannii strains were isolated from thirty-seven patients of Moscow neuro-ICU with meningitis in 2013-2020. The death rate was 37.8%. Strain susceptibility to antimicrobials was determined on the Vitek-2 instrument. Whole-genome sequencing was conducted using Illumina technology; the sequence types (ST), capsular types (KL), lipooligosaccharide outer core locus (OCL), antimicrobial resistance genes, and virulence genes were identified. The prevalent ST was ST2, belonging to the international clone IC2, and rarer, ST1, ST19, ST45, ST78, ST106, and ST400, with prevalence of KL9 and OCL1. Twenty-nine strains belonged to multidrug-resistant (MDR) and eight extensively drug-resistant (XDR) categories. Genes conferring resistance to beta-lactams (blaPER, blaGES, blaADC, blaCARB, blaCTX-M, blaTEM, and blaOXA-types), aminoglycosides (aac, aad, ant, aph, and arm), tetracyclines (tet), macrolides (msr and mph), phenicols (cml, cat, and flo), sulfonamides (dfr and sul), rifampin (arr), and antiseptics (qac) were identified. Virulence genes of nine groups (Adherence, Biofilm formation, Enzymes, Immune evasion, Iron uptake, Regulation, Serum resistance, Stress adaptation, and Antiphagocytosis) were detected. The study highlights the heterogeneity in genetic clones, antimicrobial resistance, and virulence genes variability among the agents of A. baumannii meningitis, with the prevalence of the dominant international clone IC2.

Intrapartum violence during facility-based childbirth and its determinants: A cross-sectional study among postnatal women in Tanzania.

BACKGROUND: Violence during childbirth indirectly contributes to maternal and neonatal morbidity and mortality. It also causes intrapartum health consequences such as prolonged labor, postpartum hemorrhage, and postpartum psychological problems, including postpartum depression, post-traumatic stress disorder, and other negative feelings that lead to a decreased desire for facility delivery and increase the events of home deliveries which reduce the quality of life. In Tanzania, several efforts have been made to promote respectful maternity care. However, violence during childbirth continues to create a critical barrier for facility-based delivery and is in need of considerable attention throughout the health system. OBJECTIVES: This study aimed to assess types of intrapartum violence and its determinants among postnatal women in the Dodoma Region, Tanzania. DESIGN: A cross-sectional study using a questionnaire to interview postnatal women at the exit point after being discharged from the health facility to assess intrapartum violence and its determinants. METHODS: This study was conducted in Dodoma Region involving 307 postnatal women from April to June 2022. A simple random method was used to select respondents. The Chi-square and Fisher's exact tests were used to assess the association between the categorical variables. The predictors of intrapartum violence were determined using binary logistic regression analysis. Statistical analysis was performed using Statistical Package for Social Science version 25.0. P < 0.05 was considered to be significant. RESULTS: Overall, 307 postnatal women participated in the study. Among them, 158 (51.5%) postnatal women experienced at least one form of intrapartum violence. The most common forms of intrapartum violence included breach of confidentiality 205 (66.8%), undignified care/verbal abuse 178 (58%), physical abuse 139 (45.3%), and denial or neglected care by midwives 113 (36.8%). Husband employment, urban residence, and being referred from primary hospitals were significant determinants associated with intrapartum violence (adjusted odds ratio = 0.233, 95% confidence interval = 0.057-0.952, p = 0.043, adjusted odds ratio = 2.67, 95% confidence interval = 1.13-10.93, p = 0.026 and adjusted odds ratio = 3.673, 95% confidence interval = 1.131-11.934, p = 0.030, respectively). CONCLUSION: Violence during childbirth was highly prevalent in this study. Understanding the prevalence and types of intrapartum violence is important in order to promote changes in all levels of the health system. This study reveals the need for key interventions to effect change at many levels; including an interventional study to educate women and birth partners on client rights, and strengthening the health system to meet the needs of women during labor and childbirth. Policies and systems that support respectful maternity care are urgently needed in this setting, including universal training of health professionals in respectful maternity care.

Assessing Essential New-Born Care Knowledge, Skills and Associated Factors among Nurses/Midwives in Zanzibar: A Cross-Sectional Study.

Background: Essential newborn care (ENC) is one of the significant strategies for neonatal survival, especially immediately after delivery. Nurses and midwives are the key healthcare providers who care for neonates immediately after birth, their knowledge and skills on ENC are very important for the preventable causes of neonatal deaths. Therefore, this study aimed to assess essential newborn care knowledge and skills among nurses/midwives in Zanzibar. Methods: A hospital-based analytical cross-sectional study that included 246 nurses-midwives was conducted in Zanzibar from January to February 2021. The purposive sampling method was used to select district and regional hospitals. Simple random sampling was used to select primary health facilities. A systematic random sampling technique was used to select study participants. A standard structured self-administered questionnaire was used. Predictors of knowledge and skills of ENC were determined using Binary Logistic regression under multivariate analysis using SPSS version 23.0. P<.05 was considered to be significant. Result: Among the total (246) participants, 89 (36.2%) and 66 (26.8%) had adequate knowledge and appropriate skills of ENC, respectively. Having a BSc in Nursing (AOR = 8.83, 95%CI = 2.00-38.96) and the presence of guidelines (AOR = 3.52, 95%CI = 1.59 -7.80) were significantly associated with knowledge of ENC. Residing in Pemba (AOR = 0.30, 95%CI = 0.11-0.80), availability of staff (AOR = 0.80, 95%CI = 0.02-0.32), adequate knowledge (AOR = 2.80, 95%CI = 1.15-6.84) were factors significantly associated with ENC skills. Conclusion: Generally, nurses-midwives had suboptimal knowledge and skills on essential newborn care. Nurses-midwives are in urgent need of positive supportive supervision and low-dose- high-frequency skills training in ENC for the prevention of neonatal morbidity and mortality. Also, policymakers should be aware of this gap and should plan necessary interventions to close the gap to resecure newborns' survival.

Complete Genome Sequence of Klebsiella pneumoniae Bacteriophage KpS110, Encoding Five Tail-Associated Proteins with Putative Polysaccharide Depolymerase Domains.

We report the genome sequence of bacteriophage KpS110, which infects Klebsiella pneumoniae, a multidrug-resistant encapsulated bacterium that causes severe community-acquired and hospital-acquired infections. The phage genome is 156,801 bp, with 201 open reading frames. KpS110 is most closely related to phages of the family Ackermannviridae at the genome and proteome levels.

Action of 2,6-Dichloro-1,4-benzoquinone on the O2-Evolving Activity of Photosystem II in Chlamydomonas reinhardtii Cells with and without Cell Wall: Inhibitory Effect of Its Oxidized Form.

Chlamydomonas reinhardtii is a widely used object in studies on green algae concerning both photosynthesis aspects and possible biotechnological approaches. The measurement of the maximum O2 evolution by photosystem II (PSII) in living algal cells in the presence of artificial acceptors is one of the commonly used methods for determining the photosynthetic apparatus state or its change as compared to a control, parent strain, etc., because PSII is the most sensitive component of the thylakoid membrane. The present study shows the need to use low concentrations of 2,6-dichloro-1,4-benzoquinone (DCBQ) paired with potassium ferricyanide (FeCy) for achieving the maximum O2 evolution rate, while a DCBQ concentration above certain threshold results in strong suppression of O2 evolution. The required DCBQ concentration depends on the presence of the cell wall and should be exactly ~0.1 mM or in the range of 0.2-0.4 mM for cells with and without a cell wall, respectively. The inhibition effect is caused, probably, by a higher content of DCBQ in the oxidized form inside cells; this depends on the presence of the cell wall, which influences the efficiency of DCBQ diffusion into and out of the cell, where it is maintained by FeCy in the oxidized state. The possible mechanism of DCBQ inhibition action is discussed.

High-Molecular-Weight Plasmids Carrying Carbapenemase Genes blaNDM-1, blaKPC-2, and blaOXA-48 Coexisting in Clinical Klebsiella pneumoniae Strains of ST39.

BACKGROUND: Klebsiella pneumoniae, a member of the ESKAPE group of bacterial pathogens, has developed multi-antimicrobial resistance (AMR), including resistance to carbapenems, which has increased alarmingly due to the acquisition of carbapenemase genes located on specific plasmids. METHODS: Four clinical K. pneumoniae isolates were collected from four patients of a neuro-intensive care unit in Moscow, Russia, during the point prevalence survey. The AMR phenotype was estimated using the Vitec-2 instrument, and whole genome sequencing (WGS) was done using Illumina and Nanopore technologies. RESULTS: All strains were resistant to beta-lactams, nitrofurans, fluoroquinolones, sulfonamides, aminoglycosides, and tetracyclines. WGS analysis revealed that all strains were closely related to K. pneumoniae ST39, capsular type K-23, with 99.99% chromosome identity. The novelty of the study is the description of the strains carrying simultaneously three large plasmids of the IncHI1B, IncC, and IncFIB groups carrying the carbapenemase genes of three types, blaOXA-48, blaNDM-1, and blaKPC-2, respectively. The first of them, highly identical in all strains, was a hybrid plasmid that combined two regions of the resistance genes (blaOXA-48 and blaTEM-1 + blaCTX-M-15 + blaOXA-1 + catB + qnrS1 + int1) and a region of the virulence genes (iucABCD, iutA, terC, and rmpA2::IS110). CONCLUSION: The spread of K. pneumoniae strains carrying multiple plasmids conferring resistance even to last-resort antibiotics is of great clinical concern.

The Role of Different Types of microRNA in the Pathogenesis of Breast and Prostate Cancer.

Micro ribonucleic acids (microRNAs or miRNAs) form a distinct subtype of non-coding RNA and are widely recognized as one of the most significant gene expression regulators in mammalian cells. Mechanistically, the regulation occurs through microRNA binding with its response elements in the 3'-untranslated region of target messenger RNAs (mRNAs), resulting in the post-transcriptional silencing of genes, expressing target mRNAs. Compared to small interfering RNAs, microRNAs have more complex regulatory patterns, making them suitable for fine-tuning gene expressions in different tissues. Dysregulation of microRNAs is well known as one of the causative factors in malignant cell growth. Today, there are numerous data points regarding microRNAs in different cancer transcriptomes, the specificity of microRNA expression changes in various tissues, and the predictive value of specific microRNAs as cancer biomarkers. Breast cancer (BCa) is the most common cancer in women worldwide and seriously impairs patients' physical health. Its incidence has been predicted to rise further. Mounting evidence indicates that microRNAs play key roles in tumorigenesis and development. Prostate cancer (PCa) is one of the most commonly diagnosed cancers in men. Different microRNAs play an important role in PCa. Early diagnosis of BCa and PCa using microRNAs is very useful for improving individual outcomes in the framework of predictive, preventive, and personalized (3P) medicine, thereby reducing the economic burden. This article reviews the roles of different types of microRNA in BCa and PCa progression.