The Streptomyces coelicolor small ORF trpM stimulates growth and morphological development and exerts opposite effects on actinorhodin and calcium-dependent antibiotic production

In actinomycetes, antibiotic production is often associated with a morpho-physiological differentiation program that is regulated by complex molecular and metabolic networks. Many aspects of these regulatory circuits have been already elucidated and many others still deserve further investigations. In this regard, the possible role of many small open reading frames (smORFs) in actinomycete morpho-physiological differentiation is still elusive. In Streptomyces coelicolor, inactivation of the smORF trpM (SCO2038) – whose product modulates L-tryptophan biosynthesis – impairs production of antibiotics and morphological differentiation. Indeed, it was demonstrated that TrpM is able to interact with PepA (SCO2179), a putative cytosol aminopeptidase playing a key role in antibiotic production and sporulation. In this work, a S. coelicolor trpM knock-in (Sco-trpMKI) mutant strain was generated by cloning trpM into overexpressing vector to further investigate the role of trpM in actinomycete growth and morpho-physiological differentiation. Results highlighted that trpM: (i) stimulates growth and actinorhodin (ACT) production; (ii) decreases calcium-dependent antibiotic (CDA) production; (iii) has no effect on undecylprodigiosin production. Metabolic pathways influenced by trpM knock- in were investigated by combining two-difference in gel electrophoresis/nanoliquid chromatography coupled to electrospray linear ion trap tandem mass spectrometry (2D- DIGE/nanoLC-ESI-LIT-MS/MS) and by LC-ESI-MS/MS procedures, respectively. These analyses demonstrated that over-expression of trpM causes an over-representation of factors involved in protein synthesis and nucleotide metabolism as well as a down-representation of proteins involved in central carbon and amino acid metabolism. At the metabolic level, this corresponded to a differential accumulation pattern of different amino acids – including aromatic ones but tryptophan – and central carbon intermediates. PepA was also down-represented in Sco-trpMKI. The latter was produced as recombinant His-tagged protein and was originally proven having the predicted aminopeptidase activity. Altogether, these results highlight the stimulatory effect of trpM in S. coelicolor growth and ACT biosynthesis, which are elicited through the modulation of various metabolic pathways and PepA representation, further confirming the complexity of regulatory networks that control antibiotic production in actinomycetes

Impact of low-thermal-injury devices on margin status in laryngeal cancer. An experimental ex vivo study

We conducted a prospective study on 10 excised larynges from patients affected by advanced laryngeal cancer, to assess the thermal-effect due to surgical incisions made at standard distance by using: scalpel, CO2 Laser, harmonic scalpel and electrocautery. Upon histopathological examination, thermal damage (Surgical Artifact, SA), tissue lost/retraction (Shrinkage, S), and tissue alterations were compared for each instrument

Mobilization of Hematopoietic Stem Cells with Lenograstim in Healthy Donors: Efficacy and Safety Analysis According to Donor Age

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Unravelling the DNA sequences carried by Streptomyces coelicolor membrane vesicles

Membrane vesicles (MVs) are spherical particles with nanoscale dimensions and characterized by the presence of diverse cargos, such as nucleic acids, proteins, lipids, and cellular metabolites. Many examples of (micro)organisms producing MVs are reported in literature. Among them, bacterial MVs are of particular interest because they are now considered as the fourth mechanism of horizontal gene transfer. Streptomyces bacteria are well-known for their ecological roles and ability to synthesize bioactive compounds, with Streptomyces coelicolor being the model organism. It was previously demonstrated that it can produce distinct populations of MVs characterized by different protein and metabolite cargos. In this work we demonstrated for the first time that MVs of S. coelicolor carry both DNA and RNA and that their DNA content represents the entire chromosome of the bacterium. These findings suggest that MV DNA could have a role in the evolution of Streptomyces genomes and that MVs could be exploited in new strain engineering strategies

Endoscopic nasal versus open approach for the management of sinonasal adenocarcinoma: a pooled-analysis of 1826 patients

Surgical resection represents the gold standard for the treatment of sinonasal malignancies. This study reviewed the published outcomes on endoscopic surgery or endoscopic-assisted surgery versus open approach for the management of sinonasal adenocarcinomas

Short-Term Outcomes of Polycarbophil and Propionibacterium acnes Lysate Gel after Open Hemorrhoidectomy. A Prospective Cohort Study

Background: Pain is the most common complication after open excisional hemorrhoidectomy (OEH). We assessed the effectiveness of polycarbophil and Propionibacterium acnes lysate gel (Emorsan(R)Gel) on pain control after OEH. Research design and methods: Fifty consecutive patients undergoing OEH were included. All patients received stool softeners and oral analgesia in the post-operative period. Emorsan(R)Gel was also used topically by the last 25 patients (Emorsan(R)Gel group (EG)) until Post-Operative Day 20 (POD 20). The primary outcome was the effectiveness of Emorsan(R)Gel on pain relief using an 11-point visual analogue scale (VAS). Morbidity, wound healing (WH), and time to work were documented at POD 1, POD 10, POD 20, and POD 40. Results: Of the 50 patients enrolled, twenty-eight (56%) were males; median age, 49 (range, 28-73) years. The VAS score decreased over time in all patients, with significantly lower scores at POD 20 in the EG (1.44 (SD, 1.16) vs. 2.12 (0.93) in the control group (CG); p = 0.045). All patients in the EG achieved complete WH at last follow-up, compared to only 17 (68%) in the CG (p = 0.004). The likelihood of WH was 66% higher in the EG (OR, 1.66 [95%CI, 0.80-3.44; p = 0.172). Conclusions: Emorsan(R)Gel is safe and effective at reducing pain after EOH, promoting earlier WH compared to standard care treatment

Effects of Tibetan Music on Neuroendocrine and Autonomic Functions in Patients Waiting for Surgery: A Randomized, Controlled Study

Background. The aim of this study was to investigate the effects of listening to Tibetan music on anxiety and endocrine, autonomic, cognitive responses in patients waiting for urologic surgery. Methods. Sixty patients waiting for surgery were enrolled to the study. They were randomized in music (M) and control (C) groups. The M group listened to a low-frequency Tibetan music for 30 min (T0–T30) through headphones, and the C group wore headphones with no sound. The State Trait Anxiety Inventory Questionnaire (STAI) Y-1 was administered at T0 and T30. Normalized low (LFnu) and high frequencies (HFnu) of heart rate variability, LF/HF ratio, and galvanic skin response (GRS) data were analyzed at T0, T10, T20, T30, and T35. The salivary α-amylase (sAA) samples were collected at T0, T35, and T45. Results. In the M group, the STAI Y-1 score decreased at T30 versus baseline p<0.001, sAA levels decreased at T35 versus T0p=0.004, and GSR remained unchanged. In the C group, the STAI Y-1 score remained unchanged, sAA level increased at T35 versus T0p<0.001, and GSR slightly increased at T35 versus baseline p=0.359. LFnu was lower, and HFnu was significantly higher (T10–T30) in M versus C group. Mean LF/HF ratio slightly reduced in the M group. Conclusions. Our results suggest that preoperative listening to relaxing Tibetan music might be a useful strategy to manage preoperative anxiety

Bacterial and Viral Infection and Sepsis in Kidney Transplanted Patients

Kidney transplanted patients are a unique population with intrinsic susceptibility to viral and bacterial infections, mainly (but not exclusively) due to continuous immunosuppression. In this setting, infectious episodes remain among the most important causes of death, with different risks according to the degree of immunosuppression, time after transplantation, type of infection, and patient conditions. Prevention, early diagnosis, and appropriate therapy are the goals of infective management, taking into account that some specific characteristics of transplanted patients may cause a delay (the absence of fever or inflammatory symptoms, the negativity of serological tests commonly adopted for the general population, or the atypical anatomical presentation depending on the surgical site and graft implantation). This review considers the recent available findings of the most common viral and bacterial infection in kidney transplanted patients and explores risk factors and outcomes in septic evolution