Interactions between Helcococcus kunzii and Staphylococcus aureus: How a commensal bacterium modulates the virulence and metabolism of a pathogen in a chronic wound in vitro model.

BACKGROUND: Staphylococcus aureus is the predominant pathogen isolated in diabetic foot infections. Recently, the skin commensal bacterium, Helcococcus kunzii, was found to modulate the virulence of this pathogen in an in vivo model. This study aims to elucidate the molecular mechanisms underlying the interaction between these two bacterial species, using a proteomic approach. RESULTS: Our results reveal that H. kunzii can coexist and proliferate alongside S. aureus in a Chronic Wound Media (CWM), thereby mimicking an in vitro chronic wound environment. We noted that the secreted proteome of H. kunzii induced a transcriptional effect on S. aureus virulence, resulting in a decrease in the expression level of agrA, a gene involved in quorum sensing. The observed effect could be ascribed to specific proteins secreted by H. kunzii including polysaccharide deacetylase, peptidoglycan DD-metalloendopeptidase, glyceraldehyde-3-phosphate dehydrogenase, trypsin-like peptidase, and an extracellular solute-binding protein. These proteins potentially interact with the agr system, influencing S. aureus virulence. Additionally, the virulence of S. aureus was notably affected by modifications in iron-related pathways and components of cell wall architecture in the presence of H. kunzii. Furthermore, the overall metabolism of S. aureus was reduced when cocultured with H. kunzii. CONCLUSION: Future research will focus on elucidating the role of these excreted factors in modulating virulence.

Comparative genomics analysis of two Helcococcus kunzii strains co-isolated with Staphylococcus aureus from diabetic foot ulcers.

Helcococcus kunzii is a commensal Gram-positive bacterial species recovered from the human skin microbiota and considered as an opportunistic pathogen. Although little is known about its clinical significance, its increased abundance has been reported in infected wounds, particularly in foot ulcers in persons with diabetes. This species is usually detected in mixed cultures from human specimens and frequently isolated with Staphylococcus aureus. Modulation of staphylococci virulence by H. kunzii has been shown in an infection model of Caenorhabditis elegans. The aim of this study was to compare the genomes of two H. kunzii strains isolated from foot ulcers -isolate H13 and H10 showing high or low impact on S. aureus virulence, respectively- and the H. kunzii ATCC51366 strain. Whole genome analyses revealed some differences between the two strains: length (2.06 Mb (H13) and 2.05 Mb (H10) bp), GC content (29.3% (H13) and 29.5% (H10)) and gene content (1,884 (H13) and 1,786 (H10) predicted genes). The core-proteome phylogenies within the genus characterised H. kunzii H13 and H10 as genetically similar to their ancestor. The main differences between the strains were mainly in sugar-associated transporters and various hypothetical proteins. Five targets were identified as potentially involved in S. aureus virulence modulation in both genomes: the two-component iron export system and three autoinducer-like proteins. Moreover, H13 strain harbours a prophage inserted in 1,261,110-1,295,549 (attL-attR), which is absent in H10 strain. The prophage PhiCD38_2 was previously reported for its ability to modulate secretion profile, reinforcing the autoinducer-like hypothesis. In the future, transcriptomics or metaproteomics approaches could be performed to better characterize the H13 strain and possibly identify the underlying mechanism for S. aureus virulence modulation.

Insect pest scenario in Uttarakhand Himalayas, India, under changing climatic conditions.

The Himalayan mountains are early indicators of climate change, wherein slight changes in climate can lead to a drastic variation in faunal diversity, distribution, invasion of fauna into higher altitudes, rapid population growth, shortening of life cycle and increased number of overwintering species. The insects best represent the faunal diversity. In recent years, due to variation in pattern of rainfall and temperature regimes, several insect pests have moved northwards and are posing great threat to hill agriculture. Few among them are greenhouse whiteflies, thrips and mites in protected cultivation system; blister beetles on flowers of cereals, pulses and oilseeds; invasive insect pests like fall armyworm of maize and tomato pin worm and sporadic pests like grasshoppers that are reaching a status of major key pest in various crops. Keeping in mind the phenomenon of climate change and associated changes in pest population, the present article focuses on emerging insect pest problems in cereals, millets, pulses, oilseeds and vegetables of Indian Himalayas, along with their changing population density with respect to different climatic parameters, the per cent increase in the pest damage over the years and their potential of gaining the status of major pests in near future and causing huge economic losses to hill agriculture.

Revisiting the plant growth-promoting rhizobacteria: lessons from the past and objectives for the future.

Plant beneficial rhizobacteria (PBR) is a group of naturally occurring rhizospheric microbes that enhance nutrient availability and induce biotic and abiotic stress tolerance through a wide array of mechanisms to enhance agricultural sustainability. Application of PBR has the potential to reduce worldwide requirement of agricultural chemicals and improve agro-ecological sustainability. The PBR exert their beneficial effects in three major ways; (1) fix atmospheric nitrogen and synthesize specific compounds to promote plant growth, (2) solubilize essential mineral nutrients in soils for plant uptake, and (3) produce antimicrobial substances and induce systemic resistance in host plants to protect them from biotic and abiotic stresses. Application of PBR as suitable inoculants appears to be a viable alternative technology to synthetic fertilizers and pesticides. Furthermore, PBR enhance nutrient and water use efficiency, influence dynamics of mineral recycling, and tolerance of plants to other environmental stresses by improving health of soils. This report provides comprehensive reviews and discusses beneficial effects of PBR on plant and soil health. Considering their multitude of functions to improve plant and soil health, we propose to call the plant growth-promoting bacteria (PGPR) as PBR.

Bio-efficacy of chitinolytic Bacillus thuringiensis isolates native to northwestern Indian Himalayas and their synergistic toxicity with selected insecticides.

Pesticidal properties of Bacillus thuringiensis and its associated toxic proteins is an ever-growing science with potential implications in biological pest management. In the present study 80 Bacillus thuringiensis isolates native to Uttarakhand Himalayas were evaluated for chitinolytic activity and potent ones (11 isolates) were further subjected to multiphasic characterization for their antifungal, insecticidal and synergistic properties with selected chemical insecticides. Although all the 11 potent isolates were biologically active, only three isolates (VLBt27, VLBt109 and VLBt238) showed >90% inhibition in radial growth of 3 out of 4 tested plant pathogenic fungi (Rhizoctonia solani, Fusarium oxysporum, Alternaria pori and Pyricularia oryzae). The key antagonism was manifested in the form of disruptions in growing tips and uneven mycelial thickenings. In insect bioassays (against Helicoverpa armigera, Mythimna separata and Thysanoplusia orichalcea), no considerable direct mortality was observed. However, the larval weight reduction was prominent in four isolates (VLBt27, VLBt38, VLBt109 and VLBt135) which accounts to >75% in first instar larvae of H. armigera. Joint action of these four isolates with chemical insecticides showed an overall additive interaction against Brevicoryne brassicae and synergism against H. armigera. All the isolates were compatible with tested insecticides at their field recommended doses except for chlorpyriphos with around 130 kDa protein as chitinase. The study identified VLBt27 and VLBt109, two native isolates of B. thuringiensis with potential antagonistic activity and synergism as well. These isolates have possible implications as single strategy against two diverse pest problems (pathogenic fungi and phytophagous insect) of agriculture with a view of reduced pesticide application.

Mass production of Isaria fumosorosea pfu5 for community approach management of rugose spiraling whitefly in oil palm.

The management of an alien Rugose spiraling whitefly (RSW) on oil palm using a native entomopathogenic fungus, Isaria fumosorosea pfu5 necessitated community approach for pest management. Moreover, coverage of huge leaf biomass warrants massive multiplication of biocontrol agent. In this communication, a two-step strategy, first including pure culture production and the second including ready-to-use culture production of the biocontrol agent is disclosed. The production costs and success of this technology in RSW management of oil palm are also discussed.

Growth of Ba2CoWO6single crystals and their magnetic, thermodynamic and electronic properties.

This study explores the bulk crystal growth, structural characterization, and physical property measurements of the cubic double perovskite Ba2CoWO6(BCWO). In BCWO, Co2+ions form a face-centred cubic lattice with non-distorted cobalt octahedra. The compound exhibits long-range antiferromagnetic order belowTN= 14 K. Magnetization data indicated a slight anisotropy along with a spin-flop transition at 10 kOe, a saturation field of 310 kOe and an ordered moment of 2.17µB atT= 1.6 K. Heat capacity measurements indicate an effectivej= 1/2 ground state configuration, resulting from the combined effects of the crystal electric field and spin-orbit interaction. Surface photovoltage analysis reveals two optical gaps in the UV-Visible region, suggesting potential applications in photocatalysis and photovoltaics. The magnetic and optical properties highlight the significant role of orbital contributions within BCWO, indicating various other potential applications.

Efficacy evaluation of Mongolian medical warm acupuncture for sciatica caused by lumbar disc herniation: a randomized, controlled, single-blind clinical trial.

OBJECTIVE: This study aimed to evaluate the short-term and long-term efficacy of Mongolian medical warm acupuncture for sciatica caused by lumbar disc herniation (LDH). PATIENTS AND METHODS: The patients diagnosed with sciatica caused by LDH were randomly divided into the warm acupuncture of the Mongolian medicine group (n = 42, warm acupuncture treatment), the sham acupuncture group (n = 38, sham acupuncture using blunt-tipped needles) and the conventional drug group (n = 40, ibuprofen sustained release capsule). All patients were treated for 4 weeks and followed up for 8 weeks. The visual analog scale for leg pain (VAS-LP), Mongolian medicine indicators (efficacy indicators), VAS for waist pain (VAS-WP) and the Mos 36-item short form health survey (SF-36) score were analyzed at baseline, after two-week treatment, after four-week treatment, at four-week follow-up and at eight-week follow-up. RESULTS: Warm acupuncture treatment significantly decreased the VAS-LP and VAS-WP scores of patients at treatment and follow-up (p < 0.05), and pain was improved compared to the conventional drug group and sham acupuncture group. The total effective rate was markedly higher in the warm acupuncture of the Mongolian medicine group compared with the conventional drug group at 8-week follow-up (p < 0.05), but sham acupuncture treatment resulted in no evident improvement in the Mongolian medicine indicators. Additionally, at treatment and follow-up, warm acupuncture of the Mongolian medicine group showed a significant increase in the physical function, physical role, body pain, and emotional and mental health role scores of the SF-36 survey compared with the sham acupuncture groups. CONCLUSIONS: Mongolian medical warm acupuncture effectively relieves leg and waist pain and improves the total therapeutic effect and the quality of daily life for patients with sciatica caused by LDH, with significant long-term efficacy. Our study provides a basis for warm acupuncture in the treatment of sciatica caused by LDH. Chinese Clinical Trial Registry ID: ChiCTR- INR-15007413.

INVESTIGATING TRIBUTYLTIN'S TOXIC EFFECTS: INTESTINAL BARRIER AND NEUROENTERIC DISRUPTION IN RAT'S JEJUNUM.

The expansion of economic activities in coastal areas has significantly increased chemical contamination, leading to major environmental challenges. Contaminants enter the human body through the food chain, particularly via seafood and water consumption, triggering biomagnification and bioaccumulation processes. The gastrointestinal tract (GIT) acts as a selective barrier, protecting against chemical pollutants and maintaining homeostasis through a complex network of cells and immune responses. This study assessed impact of tributyltin (TBT), a highly toxic organometallic compound used in antifouling coatings for ships, on the GIT and myenteric neural plasticity in young rats. TBT exposure leads to histopathological changes, including epithelial detachment and inflammatory foci, especially at lower environmental doses. The study found that TBT causes significant reductions in villi height, increases in goblet cells and intraepithelial lymphocytes, and disrupts the myenteric plexus, with higher densities of extraganglionic neurons in exposed animals.

First report of a small supernumerary der(8;14) marker chromosome.

Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes, generally equal in size or smaller than a chromosome 20 of the same metaphase spread. Most of them are unexpectedly detected in routine karyotype analyses, and it is usually not easy to correlate them with a specific clinical picture. A small group of sSMCs is derived from more than one chromosome, called complex sSMCs. Here, we report on a patient with a de novo complex sSMC, derived from chromosomes 8 and 14. Banding karyotype analysis, multiplex ligation-dependent probe amplification (MLPA), single nucleotide polymorphism (SNP)-based array, and fluorescence in situ hybridization (FISH) were performed to investigate its origin. Array and FISH analyses revealed a der(14)t(8;14)(p23.2;q22.1)dn. The propositus presents some clinical features commonly found in patients with partial duplication or triplication of 8p and 14q. This is the first report describing a patient with a congenital der(14)t(8;14)(p23.2;q22.1)dn sSMC.

The perspective of pharmacist on pharmacovigilance and adverse drug reaction reporting in Asir region, Saudi Arabia.

OBJECTIVE: Adverse drug reactions (ADRs) are widespread worldwide, and their intervention is critical to patient safety and healthcare quality. Pharmacists are essential in monitoring and reporting ADRs, directly influencing patient care. This study aimed to examine the prevalence of ADRs among pharmacists and their knowledge regarding ADRs, including the factors affecting ADR reporting. SUBJECTS AND METHODS: From September 2021 to November 2021, a cross-sectional survey among pharmacists in the Asir area of Saudi Arabia was planned. This study involved contacting 97 pharmacists using a cluster sampling method. The study's goals were met using a 25-item self-administered questionnaire. Data analysis was done using SPSS version 25 (IBM Corp., Armonk, NY, USA). RESULTS: Ninety-seven pharmacists (male 53.6% and female 46.4%) completed the survey. More than three-fourths of the participants (78.4%) know the ADR reporting system. The survey was completed by 97 pharmacists (male 53.6% and female 46.4%). More than three-quarters of the participants (78.4%) were aware of the ADR reporting system, and the majority (70.8%) were aware that it is done using an online system. Still, only 56.7% knew that the Saudi FDA is the regulatory agency collecting ADR data in Saudi Arabia. Furthermore, 73.2% cited stress in the workplace as a critical deterrent to reporting. Most respondents (76.3%) had an unfavorable attitude about reporting ADRs. CONCLUSIONS: Pharmacists understand ADR reporting, but most lack the mentality to report the incidents. As a result, comprehensive and ongoing training for pharmacists is required to raise awareness of the need for ADR reporting.

Proteomic insights into Helcococcus kunzii in a diabetic foot ulcer-like environment.

PURPOSE: Helcococcus kunzii is a skin commensal, Gram-positive bacterium, mostly isolated from infected chronic wounds. This opportunistic pathogen is usually co-isolated with Staphylococcus aureus. The present dataset explores the production and secretion of H. kunzii bacterial virulence interacting proteins in a growth medium mimicking chronic wounds in exponential and stationary growth phases. EXPERIMENTAL DESIGN: The H. kunzii cellular proteome and exoproteome were assessed by analyzing three biological replicates per condition tested. Samples were analyzed using a Q-Exactive HF mass spectrometer. Comparative and functional analyses were performed to profile the identified protein set. RESULTS: The H. kunzii's cellular proteome encompassed 969 proteins, among which 64 and 53 were specifically identified in the exponential and stationary phase of growth, respectively. Its exoproteome comprised 58 proteins, among which 16 and 14 were characteristic of each growth stage. Metabolic differences between the two phases of growth are discussed. Besides, the production of previously shortlisted and novel putative H. kunzii targets involved in modulating the virulence of S. aureus is investigated. CONCLUSION AND CLINICAL RELEVANCE: This work, pioneering the study of H. kunzii physiology in a chronic wound-like environment, should assist future research on this opportunistic pathogen and the search for innovative approaches for wound management.

Utilization of direct oral anticoagulants in a Saudi tertiary hospital: a retrospective cohort study.

OBJECTIVE: This study aimed to assess the appropriateness of direct oral anticoagulants (DOACs) utilization in a Saudi tertiary hospital. PATIENTS AND METHODS: Adult inpatients and outpatients diagnosed with atrial fibrillation, deep vein thrombosis, or pulmonary embolism were included in a retrospective cohort study. Patients received at least one month of apixaban, rivaroxaban, or dabigatran. The duration of the study at the Armed Forces Hospital Southern Region in Khamis Mushait, Saudi Arabia, was from January 1, 2019, to December 31, 2021. The study assessed the appropriateness of DOACs dosing, initial and follow-up monitoring, the presence of clinically significant interactions, and treatment duration adherence. RESULTS: 778 patients were included in the analysis (mean age 71.34 ± 15.98 years, equal male and female representation). Rivaroxaban was administered to 40.8% of the patients, while apixaban and dabigatran were administered to 31.02% and 28.18% of the patients, respectively. The most prevalent indication for DOACs was atrial fibrillation (72.84%), followed by deep vein thrombosis and pulmonary embolism (27.16%). The most prevalent category of medication errors was inappropriate maintenance dose (41.7%), followed by inappropriate initial dose (37.97%) and lack of laboratory parameter monitoring (36.42%). 31.5 percent of the study sample lacked baseline renal functions, while 24.5% of patients lacked baseline liver functions. 115 patients (14.8%) had potential clinically significant interactions. Regarding treatment duration, 232 patients (29.8%) were improperly prescribed DOACs based on their indications. CONCLUSIONS: In a significant proportion of DOAC patients, the prescribed rational DOAC utilization parameters were not implemented. The results of the study provide specific improvement areas and objectives for Anticoagulation stewardship programs.

Wide clinical variability in cat eye syndrome patients: four non-related patients and three patients from the same family.

A small supernumerary marker chromosome (sSMC) derived from chromosome 22 is a relatively common cytogenetic finding. This sSMC typically results in tetrasomy for a chromosomal region that spans the chromosome 22p arm and the proximal 2 Mb of 22q11.21. Using classical cytogenetics, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and array techniques, 7 patients with sSMCs derived from chromosome 22 were studied: 4 non-related and 3 from the same family (mother, daughter, and son). The sSMCs in all patients were dicentric and bisatellited chromosomes with breakpoints in the chromosome 22 low-copy repeat A region, resulting in cat eye syndrome (CES) due to chromosome 22 partial tetrasomy 22pter→q11.2 including the cat eye chromosome region. Although all subjects presented the same chromosomal abnormality, they showed a wide range of phenotypic differences, even in the 3 patients from the same family. There are no previous reports of CES occurring within 3 patients in the same family. Thus, the clinical and follow-up data presented here contribute to a better delineation of the phenotypes and outcomes of CES patients and will be useful for genetic counseling.

Bacterial Interactions in the Context of Chronic Wound Biofilm: A Review.

Chronic wounds, defined by their resistance to care after four weeks, are a major concern, affecting millions of patients every year. They can be divided into three types of lesions: diabetic foot ulcers (DFU), pressure ulcers (PU), and venous/arterial ulcers. Once established, the classical treatment for chronic wounds includes tissue debridement at regular intervals to decrease biofilm mass constituted by microorganisms physiologically colonizing the wound. This particular niche hosts a dynamic bacterial population constituting the bed of interaction between the various microorganisms. The temporal reshuffle of biofilm relies on an organized architecture. Microbial community turnover is mainly associated with debridement (allowing transitioning from one major representant to another), but also with microbial competition and/or collaboration within wounds. This complex network of species and interactions has the potential, through diversity in antagonist and/or synergistic crosstalk, to accelerate, delay, or worsen wound healing. Understanding these interactions between microorganisms encountered in this clinical situation is essential to improve the management of chronic wounds.

Expression of insulin-like growth factor-II, matrix metalloproteinases, and their tissue inhibitors as predictive markers in the peripheral blood of HCC patients.

BACKGROUND/AIM: Elevated relative expression of insulin-like growth factor-II (IGF-II) was observed in hepatocellular carcinoma (HCC) liver tissues with a role in neovascularization and associated with poor prognosis. IGF-II is influenced by the proteolytic cleavage of IGF-binding protein 3 and by matrix metalloproteinases (MMP), which are further regulated by their tissue inhibitors tissue inhibitor of metalloprotienase-1 (TIMP-1). Our aim is to study new molecular markers for HCC. PATIENTS/METHODS: RNA was extracted from the peripheral blood for evaluating the relative expression of IGF-II, MMP-9, and TIMP-1 in correlation with clinical staging of 39 HCC patients and 15 healthy controls using TaqMan real-time PCR. RESULTS: The relative expression of IGF-II and MMP-9 mRNA were significantly elevated in HCC patients compared with healthy controls; P-value <0.0001 for both. There was a significant correlation between MMP-9 and different HCC stages. On the other hand, TIMP-1 was significantly down-regulated in HCC patients; P = 0.0003 with the elevation of the IGF-II/TIMP-1 ratio. Significant correlation between TIMP-1 and HCC Stage III and Stage IV was found; P-value = 0.0138. CONCLUSION: These results highlight the importance of profiling the expression of IGF-II, MMP-9, and TIMP-1 in the peripheral blood as prognostic molecular biomarkers in HCC.

Protocol for 18F-FDG quantification in PET-CT whole-body exams.

The aim of the present work is to propose a protocol for quantification of (18)F-FDG activities at organ level through whole body exams with Positron Emission Tomography. They were selected patients with normal uptake or a single tumor. In the period 2004-2005, 745 patients were studied. Among then, it was selected 97 adults for the normal uptake control group. The main studies were: intestine; colon, rectum, lung, lymphoma and melanoma, liver, esophagus, gonads and breasts. For "prospective screening", it were selected 20 patients with the identical physical characteristics of the control group. For internal dosimetry, the main organs should be elected according the kinetics of (18)F-FDG, either considering normal uptake or pathologies. Absorbed doses due to Computed Tomography and F-FDG uptake were estimated. Comparisons between internal and external exposures, for the same organ, point out higher doses due to external irradiation, except for bladder and kidneys. For individual dose estimation, parameters such the effective half-life should be known and this information may be achieved by an adaptation of the routine protocol.

Internal root morphology of the maxillary first premolars in Kenyans of African descent.

OBJECTIVE: To determine the internal root morphology of the maxillary first premolar in Kenyans of African descent. DESIGN: In vitro descriptive cross-sectional study. SETTING: School of Dental Sciences, University of Nairobi. SUBJECTS: One hundred and fifty five extracted maxillary first premolars obtained from patients aged between 13-30 years attending dental clinics within Nairobi. RESULTS: There were 77 premolars from males and 78 from females. Majority (87.1%) of the teeth had two canals. Males presented with three canals more commonly than females. This difference was statistically significant. According to Vertucci's classification, male specimens demonstrated five of the canals types while female specimens demonstrated all the eight canal types. These differences were not statistically significant. CONCLUSIONS: Kenyan maxillary first premolar was mostly found to have two canals. There were eight canal types, with type IV being the commonest.

Hereditary gingival fibromatosis: report of family case series.

Hereditary gingival hyperplasia (HGF) is a rare condition characterised by hyperplastic, dense fibrous connective tissue with acanthotic gingival epithelium. A family presented at the School of Dental Sciences, University of Nairobi with a complaint that some of the children developed swollen gums very early in life and that this got worse with eruption of the permanent teeth. The first born, a 23-year-old male, had had the swellings for over ten years. Other siblings aged 5, 9 and 12 years were also affected. The swellings had affected the appearance, speech and the psychosocial wellbeing of the children. The parents were unaffected with apparently negative family histories. Following oral examination and appropriate investigations, conventional gingivectomy was performed of the maxillary and the mandibular gingivae for the siblings: the 23- 12- and the nine-year olds. The fourth affected child, a five-year-old, was still in primary dentition and had just started showing mild signs of gingival hyperplasia. The histopathological examination of the specimens from the present cases confirmed features consistent with those of HGF. This article highlights a familial presentation of HGF.