A systematic review and meta-analysis of systematic and topical tranexamic acid administration in aesthetic plastic surgery.

INTRODUCTION: Tranexamic acid has been widely used in plastic surgery. However, its efficacy has yet to be fully established. This meta-analysis aimed to determine its effectiveness in aesthetic plastic surgery. METHODS: Following PRISMA guidelines, we conducted a meta-analysis of prospective randomised clinical trials that compared the effects of topical or systematic administration of tranexamic acid versus the control group in aesthetic plastic surgeries. The study was registered on the International Register of Systematic Reviews (PROSPERO) and is available online ( www.crd.york.uk/prospero , CRD42023492585). RESULTS: Eleven studies encompassing 960 patients were included for the synthesis after critical evaluation. Systematic (MD - 18.05, 95% Cl, - 22.01, - 14.09, p < 0.00001) and topical (MD - 74.93, 95% Cl, - 88.79, - 61.07, p < 0.00001) administration of tranexamic acid reduced total blood loss. Topical tranexamic acid reduced drainage output (p < 0.0006). CONCLUSION: Tranexamic acid reduced blood loss in aesthetic plastic surgery. More strictly defined RCTs, using high-quality methodology, are needed to evaluate the advantages and disadvantages of tranexamic acid in aesthetic plastic surgery.

Effectiveness of the Bilateral and Bilevel Erector Spinae Plane Block (ESPB) in Pediatric Idiopathic Scoliosis Surgery: A Randomized, Double-Blinded, Controlled Trial.

BACKGROUND: This study aimed to compare the effect of the ultrasound-guided bilateral and bilevel erector spinae plane block (ESPB) on pain scores, opioid requirement, intraoperative motor-evoked potentials (MEPs), and stress response to surgery expressed by the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) versus standard analgesia methods following idiopathic scoliosis surgery. METHODS: This was a prospective, double-blinded, randomized controlled trial. Sixty patients aged 10 to 18 years and physical status ASA 1 or 2 were randomized into 2 equal groups, each receiving an ESPB or sham block. The primary outcome was the pain scores (Numerical Rating Scale, NRS) within 48 hours after spinal correction and fusion surgery for idiopathic thoracic scoliosis. The secondary outcomes were total opioid consumption, NLR, and PLR levels at 12 and 24 hours postoperatively and intraoperative MEPs. RESULTS: ESPB patients presented lower NRS scores, signifying less pain, at all time points (30, 60, 90, 120 min; and 6, 12, 24, and 48 h after surgery), all P <0.0001. The total opioid consumption, the incidence of nausea or vomiting, and the need for remifentanil and propofol during surgery were significantly lower in the ESPB group. The surgery-induced stress response expressed by NLR and PLR was considerably lower in the ESPB group. ESPB did not affect the intraoperative MEP's amplitude. CONCLUSIONS: ESPB is effective for postoperative analgesia, can reduce opioid consumption in patients undergoing scoliosis surgery, and reduces the stress response to surgery. ESPB does not interfere with neuromonitoring. LEVEL OF EVIDENCE: Level I.

Persistent T cell unresponsiveness associated with chronic visceral leishmaniasis in HIV-coinfected patients.

A large proportion of HIV-coinfected visceral leishmaniasis (VL-HIV) patients exhibit chronic disease with frequent VL recurrence. However, knowledge on immunological determinants underlying the disease course is scarce. We longitudinally profiled the circulatory cellular immunity of an Ethiopian HIV cohort that included VL developers. We show that chronic VL-HIV patients exhibit high and persistent levels of TIGIT and PD-1 on CD8+/CD8- T cells, in addition to a lower frequency of IFN-γ+ TIGIT- CD8+/CD8- T cells, suggestive of impaired T cell functionality. At single T cell transcriptome and clonal resolution, the patients show CD4+ T cell anergy, characterised by a lack of T cell activation and lymphoproliferative response. These findings suggest that PD-1 and TIGIT play a pivotal role in VL-HIV chronicity, and may be further explored for patient risk stratification. Our findings provide a strong rationale for adjunctive immunotherapy for the treatment of chronic VL-HIV patients to break the recurrent disease cycle.

Source Tracing of Leishmania donovani in Emerging Foci of Visceral Leishmaniasis, Western Nepal.

We sequenced Leishmania donovani genomes in blood samples collected in emerging foci of visceral leishmaniasis in western Nepal. We detected lineages very different from the preelimination main parasite population, including a new lineage and a rare one previously reported in eastern Nepal. Our findings underscore the need for genomic surveillance.

Analgesic Efficacy of Oxycodone in Postoperative Dressings after Surgical Treatment of Burn Wounds: A Randomised Controlled Trial.

INTRODUCTION: This study aimed to assess the analgesic efficacy of oxycodone at doses of 10 mg and 20 mg in dressings after surgery of burn wounds. MATERIAL AND METHODS: Twenty adult patients who underwent surgical treatment of third-degree burn wounds under general anaesthesia were included. Burn wounds were treated with dressings, to which oxycodone was added at 20 mg in Group 1 and 10 mg in Group 2. After the surgery, plasma oxycodone and noroxycodone concentrations were assayed, and pain intensity was assessed with Numerical Rating Scale (NRS). RESULTS: In Group 1, no patient reported pain; in Group 2, four patients reported pain. The pain intensity, according to NRS, was 1-8. Plasma concentration of oxycodone in the blood serum was in the range of 1.24-3.15 ng/mL and 1.09-1.28 ng/mL in Group 1 and Group 2, respectively. Noroxycodone was not detected in the plasma. Adverse effects were not observed in any of the treated patients. CONCLUSIONS: Oxycodone in dressings provides patients with adequate and safe analgesia.

Morphine (10, 20 mg) in a Postoperative Dressing Used with Patients After Surgical Debridement of Burn Wounds: A Prospective, Double-Blinded, Randomized Controlled Trial.

Objective: This is the first clinical trial to evaluate the analgesic effect of 10 and 20 mg of morphine used in a postoperative dressing with patients after surgical debridement of burn wounds. Approach: In this randomized controlled trial, 20 adult patients with third-degree flame burns, who had undergone surgical debridement under general anesthesia, were randomly assigned to either group A, whose members were treated with a burn dressing that contained 10 mg of morphine, or group B, whose members were treated with a burn dressing that contained 20 mg of morphine; the dressing was also soaked with octenidine and phenoxyethanol in the case of both groups. The plasma morphine concentrations were measured 1, 2, 3, and 6 h after surgery, while the level of pain intensity was determined on the Numeric Pain Rating Scale (NRS), and the occurrence of side effects was observed. Results: The serum morphine concentration levels were very low, but statistically different between the two groups at all time points. The NRS value was similar in both groups at all time points (p > 0.05). Despite this, in group B, the NRS value was 0 in all patients in postoperative hours 1, 2, and 3. No adverse effect of morphine sulfate was observed in any patient. Innovation: This project is the first clinical study to have demonstrated that morphine administered in dressings in concentrations of 0.02-0.08 mg/mL significantly reduces the occurrence of pain. Conclusion: The use of morphine in dressings after surgical treatment of burn wounds is very effective when it comes to pain management and is safe for the patient.

Periarticular injection, iPACK block, and peripheral nerve block in pain management after total knee arthroplasty: a structured narrative review.

INTRODUCTION: Total knee arthroplasty (TKA) is commonly performed in patients with end-stage osteoarthritis or rheumatoid arthritis of the knee to reduce joint pain, increase mobility, and improve quality of life. However, TKA is associated with moderate to severe postoperative pain, which remains a significant clinical challenge. Surgeon-administered PAI and anesthesiologist-administered iPACK have proven viable alternatives to conventional peripheral nerve blocks. This review aims to discuss which IPACK block or periarticular injection, combined or not with different peripheral nerve blocks, has better effects on postoperative rehabilitation, patient satisfaction, and overall outcome. MATERIAL AND METHODS: The literature review was performed on standards of care, current therapeutic options, a pain management protocol, and innovative treatment options for patients undergoing total knee arthroplasty. The literature was reviewed through four electronic databases: PubMed, Cochrane Library, Google Scholar, and Embase. RESULTS: The initial search yielded 694 articles. Fifty relevant articles were selected based on relevance, recentness, search quality, and citations. Six studies compared PAI to peripheral nerve block (PNB), and eight studies checked the effectiveness of adding PNB to PAI. Three studies compared iPACK to PNB, and ten reviewed the point of adding PNB to iPACK. CONCLUSIONS: The literature review indicates that the best analgesic effect is obtained by combining PAI or iPACK with a peripheral nerve block, particularly with ACB, due to its analgesic, motor-sparing effect, and satisfactory analgesia.

Pain Management, Functional Recovery, and Stress Response Expressed by NLR and PLR after the iPACK Block Combined with Adductor Canal Block for Total Knee Arthroplasty-A Prospective, Randomised, Double-Blinded Clinical Trial.

INTRODUCTION: This study aimed to investigate pain management, functional recovery, and stress response expressed by the neutrophile-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) after the popliteal artery and posterior knee capsule infiltration (iPACK) block combined with adductor canal block (ACB) in total knee arthroplasty (TKA). PATIENTS AND METHODS: This was a prospective, double-blinded, randomised, controlled trial in a tertiary referral hospital. Three hundred and sixty-six patients were randomly allocated into the sham block group and iPACK combined with the ACB group. The primary outcome was postoperative pain scores. The secondary outcomes were opioid consumption, functional recovery expressed by a range of motion, and quadriceps strength. Also, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated. RESULTS: There were significant differences between the sham block and iPACK + ACB group in pain scores p < 0.0001 at all time points. Therefore, there was a significant difference in opioid consumption (p < 0.0001) and functional recovery (p < 0.0001). Also, NLR and PLR levels 12 h (p < 0.0001) and 24 h (24 h) after surgery (p < 0.0001) were much lower in the iPACK + ACB group. CONCLUSION: After total knee arthroplasty, the iPACK combined with ACB block group improved pain management, functional recovery, and stress response. Therefore, we strongly recommend this technique as a part of a multimodal analgesia protocol in knee surgery.

Unveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasis.

Introduction: Resistance against anti-Leishmania drugs (DR) has been studied for years, giving important insights into long-term adaptations of these parasites to drugs, through genetic modifications. However, microorganisms can also survive lethal drug exposure by entering into temporary quiescence, a phenomenon called drug tolerance (DT), which is rather unexplored in Leishmania. Methods: We studied a panel of nine Leishmania braziliensis strains highly susceptible to potassium antimonyl tartrate (PAT), exposed promastigotes to lethal PAT pressure, and compared several cellular and molecular parameters distinguishing DT from DR. Results and discussion: We demonstrated in vitro that a variable proportion of cells remained viable, showing all the criteria of DT and not of DR: i) signatures of quiescence, under drug pressure: reduced proliferation and significant decrease of rDNA transcription; ii) reversibility of the phenotype: return to low IC50 after removal of drug pressure; and iii) absence of significant genetic differences between exposed and unexposed lineages of each strain and absence of reported markers of DR. We found different levels of quiescence and DT among the different L. braziliensis strains. We provide here a new in-vitro model of drug-induced quiescence and DT in Leishmania. Research should be extended in vivo, but the current model could be further exploited to support R&D, for instance, to guide the screening of compounds to overcome the quiescence resilience of the parasite, thereby improving the therapy of leishmaniasis.

Comparison of Motor Evoked Potentials Neuromonitoring Following Pre- and Postoperative Transcranial Magnetic Stimulation and Intraoperative Electrical Stimulation in Patients Undergoing Surgical Correction of Idiopathic Scoliosis.

The relationships between the results of pre- and intraoperative motor evoked potential recordings during neuromonitoring and whether idiopathic scoliosis (IS) surgical correction improves the spinal efferent transmission have not been specified in detail. This study aims to compare the results of surface-recorded electromyography (EMG), electroneurography (ENG, M, and F-waves), and especially motor evoked potential (MEP) recordings from tibialis anterior muscle (TA) bilaterally in 353 girls with right idiopathic scoliosis (types 1-3 according to Lenke classification). It has not yet been documented whether the results of MEP recordings induced by transcranial single magnetic stimulus (TMS, pre- and postoperatively) and trains of electrical stimuli (TES; intraoperatively in T0-before surgery, T1-after pedicle screws implantation, and T2-after scoliosis curvature distraction and derotation following two-rod implantation) can be compared for diagnostic verification of the improvement of spinal cord neural transmission. We attempted to determine whether the constant level of optimal anesthesia during certain surgical steps of scoliosis treatment affects the parameters of MEPs recorded during neuromonitoring procedures. No neurological deficits have been observed postoperatively. The values of amplitudes but not latencies in MEP recordings evoked with TMS in IS patients compared before and after surgery indicated a slight improvement in efferent neural transmission. The results of all neurophysiological studies in IS patients were significantly asymmetrical and recorded worse on the concave side, suggesting greater neurological motor deficits at p = 0.04. The surgeries brought significant improvement (p = 0.04) in the parameters of amplitudes of sEMG recordings; however, the consequences of abnormalities in the activity of TA motor units were still reflected. ENG study results showed the symptoms of the axonal-type injury in peroneal motor fibers improving only on the concave side at p = 0.04, in parallel with F-wave parameters, which suggests that derotation and distraction might result in restoring the proper relations of the lumbar ventral roots in the spinal central canal, resembling their decompression. There were no significant differences detected in the amplitudes or latencies of MEPs induced with TMS or TES when comparing the parameters recorded preoperatively and intraoperatively in T0. The amplitudes of TES-evoked MEPs increased gradually at p = 0.04 in the subsequent periods (T1 and T2) of observation. A reduction in MEP latency at p = 0.05 was observed only at the end of the IS surgery. Studies on the possible connections between the level of anesthesia fluctuations and the required TMS stimulus strength, as well as the MEP amplitude changes measured in T0-T2, revealed a lack of relationships. These might not be the factors influencing the efferent transmission in spinal pathways beside the surgical procedures. Pre- (TMS-evoked) and intraoperative (TES-evoked) recordings are reliable for evaluating the patient's neurological status before and during surgical scoliosis correction procedures. An increase in MEP amplitude parameters recorded on both sides after scoliosis surgery proves the immediate improvement of the total efferent spinal cord transmission. Considering comparative pre- and postoperative sEMG and ENG recordings, it can be concluded that surgeries might directly result in additional lumbar ventral root decompression. We can conclude that MEP parameter changes are determined by the surgery procedures during neuromonitoring, not the anesthesia conditions if they are kept stable, which influences a decrease in the number of false-positive neuromonitoring warnings.

The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) levels following erector spinae plane block (ESPB) in posterior lumbar decompression: a randomized, controlled trial.

PURPOSE: Neutrophile-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are the inflammatory biomarkers of the stress response. In this study, we aimed to evaluate the effects of erector spinae plane block (ESPB) on posterior lumbar decompression and stabilization by comparing NLR, PLR, postoperative pain, opioid consumption, and functional recovery between sham block and ESPB. METHODS: This was a prospective, double-blinded, randomized controlled trial in a tertiary referral hospital. Sixty patients were randomized into two equal groups, each receiving either a sham block or ESPB. The primary outcome was the NLR and PLR 12 h and 24 h after lumbar posterior decompression and stabilization. The secondary outcomes were total opioid consumption and pain score 24 h postoperatively. Also, functional recovery determined by getting out of bed, verticalization, and walking by the balcony were reviewed as secondary outcomes. RESULTS: Significant differences existed between the sham block and ESPB group in NLR (29.08 ± 12.29 vs. 16.97 ± 10.38; p < 0.0001) and PLR (556.77 ± 110.32 vs. 346.43 ± 117.34; p < 0.0001) 12 h after surgery. Also, there was a significant difference in NLR (p = 0.0466) and PLR (p < 0.0001) 24 h after surgery. In addition, there was a substantial difference in pain score, total opioid consumption, and functional recovery. CONCLUSION: ESPB performance during spinal surgery lowers NRL and PLR ratios 12 h and 24 h after surgery. In addition, ESPB provides better analgesia and improves functional recovery compared to sham block following posterior lumbar decompression and stabilization.

Bilateral Bi-Level Erector Spinae Plane Blocks as a Part of Opioid-Sparing Multimodal Analgesia in Scoliosis Surgery: A Case Series of Six Pediatric Patients.

Background and Aim: Postoperative pain after scoliosis surgery is severe and usually requires long-term intravenous opioid therapy. Local anesthetic options, such as wound infiltration, are limited and include neuraxial analgesia. However, they are rarely used due to side effects and inconsistent efficacy. We report an opioid-sparing multimodal analgesia regimen with bilateral erector spinae plane blocks. This case series evaluated the analgesic effect of the bilateral bi-level erector spinae plane blocks (ESP) in congenital and neurogenic scoliosis surgery. Patients and Methods: Six pediatric patients with congenital or neurogenic scoliosis underwent posterior spinal fusion involving 5 to 12 vertebral levels. Bilateral single-injection ESPB was performed at one or two levels before incision. Preoperatively, patients received intravenous dexamethasone. General anesthesia with endotracheal intubation and volume-controlled ventilation was performed via TIVA with remifentanil and propofol. During and after the procedure, the basic hemodynamic parameters, opioid consumption, pain scores (numerical rating scale/NRS), and possible block complications were monitored. Results: All the patients experienced minimal postoperative pain levels. In addition, on the first day after surgery, they had low opioid requirements with no side effects. Conclusions: ESPB in patients undergoing congenital and neurogenic scoliosis correction surgery seems to be an essential analgesic technique that may reduce both severities of pain and opioid consumption.

Pain Management and Functional Recovery after Pericapsular Nerve Group (PENG) Block for Total Hip Arthroplasty: A Prospective, Randomized, Double-Blinded Clinical Trial.

BACKGROUND: The immediate postoperative period after total hip arthroplasty can be associated with significant pain. Therefore, this study aimed to evaluate the effect of pericapsular nerve block on pain management and functional recovery after total hip arthroplasty. METHODS: This prospective, randomized, double-blinded, placebo-controlled trial was conducted on 489 adult patients scheduled for total hip arthroplasty, ASA 1-2, operated under spinal analgesia. Participants were assigned to receive either a pericapsular nerve group (PENG) block with 20 mL of 0.5% ropivacaine or a sham block. RESULTS: The primary outcome measure was the postoperative NRS score in motion. The secondary outcomes were cumulative opioid consumption, the time to the first opioid, and functional recovery. Demographic characteristics were similar in both groups. Intraoperative pain scores were significantly lower in patients who received the PENG block than in the control group (p < 0.0001). Also, the time to the first opioid was considerably longer in the PENG group (p < 0.0001). Additionally, 24% of PENG patients did not require opioids (p < 0.0001). CONCLUSIONS: The pericapsular nerve group showed significantly decreased opioid consumption and improved functional recovery. Pericapsular nerve group block improved pain management and postoperative functional recovery following total hip arthroplasty.

The adaptive roles of aneuploidy and polyclonality in Leishmania in response to environmental stress.

Aneuploidy is generally considered harmful, but in some microorganisms, it can act as an adaptive mechanism against environmental stress. Here, we use Leishmania-a protozoan parasite with remarkable genome plasticity-to study the early steps of aneuploidy evolution under high drug pressure (using antimony or miltefosine as stressors). By combining single-cell genomics, lineage tracing with cellular barcodes, and longitudinal genome characterization, we reveal that aneuploidy changes under antimony pressure result from polyclonal selection of pre-existing karyotypes, complemented by further and rapid de novo alterations in chromosome copy number along evolution. In the case of miltefosine, early parasite adaptation is associated with independent point mutations in a miltefosine transporter gene, while aneuploidy changes only emerge later, upon exposure to increased drug levels. Therefore, polyclonality and genome plasticity are hallmarks of parasite adaptation, but the scenario of aneuploidy dynamics depends on the nature and strength of the environmental stress as well as on the existence of other pre-adaptive mechanisms.

Genome diversity of Leishmania aethiopica.

Leishmania aethiopica is a zoonotic Old World parasite transmitted by Phlebotomine sand flies and causing cutaneous leishmaniasis in Ethiopia and Kenya. Despite a range of clinical manifestations and a high prevalence of treatment failure, L. aethiopica is one of the most neglected species of the Leishmania genus in terms of scientific attention. Here, we explored the genome diversity of L. aethiopica by analyzing the genomes of twenty isolates from Ethiopia. Phylogenomic analyses identified two strains as interspecific hybrids involving L. aethiopica as one parent and L. donovani and L. tropica respectively as the other parent. High levels of genome-wide heterozygosity suggest that these two hybrids are equivalent to F1 progeny that propagated mitotically since the initial hybridization event. Analyses of allelic read depths further revealed that the L. aethiopica - L. tropica hybrid was diploid and the L. aethiopica - L. donovani hybrid was triploid, as has been described for other interspecific Leishmania hybrids. When focusing on L. aethiopica, we show that this species is genetically highly diverse and consists of both asexually evolving strains and groups of recombining parasites. A remarkable observation is that some L. aethiopica strains showed an extensive loss of heterozygosity across large regions of the nuclear genome, which likely arose from gene conversion/mitotic recombination. Hence, our prospection of L. aethiopica genomics revealed new insights into the genomic consequences of both meiotic and mitotic recombination in Leishmania.

A non-canonical function of Arabidopsis ERECTA proteins and a role of the SWI3B subunit of the SWI/SNF chromatin remodeling complex in gibberellin signaling.

The Arabidopsis ERECTA family (ERf) of leucine-rich repeat receptor-like kinases (LRR-RLKs) comprising ERECTA (ER), ERECTA-LIKE 1 (ERL1), and ERECTA-LIKE 2 (ERL2) controls epidermal patterning, inflorescence architecture, and stomata development and patterning. These proteins are reported to be plasma membrane associated. Here we show that the er/erl1/erl2 mutant exhibits impaired gibberellin (GA) biosynthesis and perception alongside broad transcriptional changes. The ERf kinase domains were found to localize to the nucleus where they interact with the SWI3B subunit of the SWI/SNF chromatin remodeling complex (CRCs). The er/erl1/erl2 mutant exhibits reduced SWI3B protein level and affected nucleosomal chromatin structure. Similar to swi3c and brm plants with inactivated subunits of SWI/SNF CRCs, it also does not accumulate DELLA RGA and GAI proteins. The ER kinase phosphorylates SWI3B in vitro, and the inactivation of all ERf proteins leads to the decreased phosphorylation of SWI3B protein in vivo. The identified correlation between DELLA overaccumulation and SWI3B proteasomal degradation, and the physical interaction of SWI3B with DELLA proteins indicate an important role of SWI3B-containing SWI/SNF CRCs in gibberellin signaling. Co-localization of ER and SWI3B on GID1 (GIBBERELLIN INSENSITIVE DWARF 1) DELLA target gene promoter regions and abolished SWI3B binding to GID1 promoters in er/erl1/erl2 plants supports the conclusion that ERf-SWI/SNF CRC interaction is important for transcriptional control of GA receptors. Thus, the involvement of ERf proteins in the transcriptional control of gene expression, and observed similar features for human HER2 (epidermal growth family receptor member), indicate an exciting target for further studies of evolutionarily conserved non-canonical functions of eukaryotic membrane receptors.

Pericapsular Nerves Group (PENG) Block in Children under Five Years of Age for Analgesia in Surgery for Hip Dysplasia: Case Report.

INTRODUCTION: The Pericapsular Nerve Group (PENG) block is a novel technique that allows for analgesia of the anterior hip capsule via the articular branches of the accessory obturator nerve and femoral nerve, which have a significant role in the innervation of the hip capsule. A PENG (Pericapsular Nerves Group) blockade is effective in both adult and pediatric patients. However, no studies on patients under five are available in the literature. Herein, we describe our experience with two pediatric patients with hip dysplasia. PURPOSE: This study aimed to evaluate the analgesic effect of the pericapsular nerves group (PENG) in preschool children undergoing hip surgery. PATIENTS AND METHODS: This study included two patients, aged 4 and 2 years old, who were qualified for hip surgery. Spinal or general anesthesia with the addition of a PENG block was performed. During the procedure, the basic hemodynamic parameters were monitored. The pain was assessed using the FALCC (Face, Legs, Activity, Cry, Consolability scale) score. A dose of 15 mg/kg-1 of metamizole was administered if the FLACC score was 3. In the case of a score of 4 on the FLACC scale, the application of 0.2 mg/kg-1 of nalbuphine was ordered. RESULTS: After the surgery, the patients received 15 mg/kg-1 IV paracetamol every 6 h to prevent rebound pain. The patient's hemodynamic parameters were stable and within normal range. In the first 24 h period, the FLACC scores from all patients ranged from 0 to 3. One patient required metamizole 12 h after surgery. No evidence of block complications was observed. CONCLUSIONS: This case series showed that the PENG block assured opioid-free pain management and provided adequate postoperative analgesia. However, we are convinced that future randomized, controlled trials are needed in this field.

Drug resistance in Leishmania: does it really matter?

Treatment failure (TF) jeopardizes the management of parasitic diseases, including leishmaniasis. From the parasite's point of view, drug resistance (DR) is generally considered as central to TF. However, the link between TF and DR, as measured by in vitro drug susceptibility assays, is unclear, some studies revealing an association between treatment outcome and drug susceptibility, others not. Here we address three fundamental questions aiming to shed light on these ambiguities. First, are the right assays being used to measure DR? Second, are the parasites studied, which are generally those that adapt to in vitro culture, actually appropriate? Finally, are other parasite factors - such as the development of quiescent forms that are recalcitrant to drugs - responsible for TF without DR?

Four layer multi-omics reveals molecular responses to aneuploidy in Leishmania.

Aneuploidy causes system-wide disruptions in the stochiometric balances of transcripts, proteins, and metabolites, often resulting in detrimental effects for the organism. The protozoan parasite Leishmania has an unusually high tolerance for aneuploidy, but the molecular and functional consequences for the pathogen remain poorly understood. Here, we addressed this question in vitro and present the first integrated analysis of the genome, transcriptome, proteome, and metabolome of highly aneuploid Leishmania donovani strains. Our analyses unambiguously establish that aneuploidy in Leishmania proportionally impacts the average transcript- and protein abundance levels of affected chromosomes, ultimately correlating with the degree of metabolic differences between closely related aneuploid strains. This proportionality was present in both proliferative and non-proliferative in vitro promastigotes. However, as in other Eukaryotes, we observed attenuation of dosage effects for protein complex subunits and in addition, non-cytoplasmic proteins. Differentially expressed transcripts and proteins between aneuploid Leishmania strains also originated from non-aneuploid chromosomes. At protein level, these were enriched for proteins involved in protein metabolism, such as chaperones and chaperonins, peptidases, and heat-shock proteins. In conclusion, our results further support the view that aneuploidy in Leishmania can be adaptive. Additionally, we believe that the high karyotype diversity in vitro and absence of classical transcriptional regulation make Leishmania an attractive model to study processes of protein homeostasis in the context of aneuploidy and beyond.

Physical activity induced alterations of gut microbiota in humans: a systematic review.

BACKGROUND: Gut microbiota is considered to have a great impact on human health and disease. While it is widely recognized that the gut microbiota of healthy individuals differs from those with obesity, inflammatory bowel disease, metabolic syndrome, and other chronic diseases, the alterations of gut microbiota with physical activity are not fully understood. Accordingly, we performed this systematic review to address the question regarding the effects of mild and intense exercise on the gut microbiota in humans. METHODS: The comparative analyses of gut microbiota were conducted following the PRISMA protocol to determine the differences in the active vs. non-active individuals (phenotypes) (n = 11), including the influence of physical activity intervention on the human gut microbiota (n = 13); the differences in the gut microbiota of athletes vs. non-athletes (n = 8); and the microbiota status at different stages of athletic performance or intervention (n = 7), with various of physical activities, sport disciplines, and activity duration. Literature searches were completed using four databases: PubMed, Web of Science, Scopus, and EBSCO, and 2090 articles were retrieved by using appropriate keywords. The low heterogeneity of the studies hasn't allowed us to prepare a meta-analysis. After excluding 2052 articles, we ultimately selected 38 articles that met the eligibility criteria for this review. RESULTS: The data analyses revealed that in non-athletes rising physical activity markedly influenced the relative abundance of short-chain fatty acid (SCFA). Aerobic training that lasted 60 min, and physical activity that characterized 60% HRmax or more also influenced beta diversity indexes. The results showed that athletes harbor a more diverse type of intestinal microflora than non-athletes, but with a relatively reduced abundance of SCFA- and lactic acid-producing bacteria, thereby suggesting an adverse effect of intense exercise on the population of gut microbiota. CONCLUSION: It is concluded that the level of physical activity modulates the gastrointestinal microbiota in humans. For a long period, increasing the intensity and volume of exercise may lead to gut dysbiosis. Perhaps, proper supplementation should be considered to keep gut microbiota in large biodiversity and richness, especially under unfavorable gut conditions associated with intense exercise. TRIAL REGISTRATION: Prospero CRD42021264064.