δ-Lactones—A New Class of Compounds That Are Toxic to E. coli K12 and R2–R4 Strains

Lactones are among the well-known organic substances with a specific taste and smell. They are characterized by antibacterial, antiviral, anti-inflammatory, and anti-cancer properties. In recent years, among this group of compounds, new biologically active substances have been searched by modifying the main (leading) structure with new analogs with stronger or different responses that may have a toxic effect on the cells of pathogenic bacteria and constitute an alternative to commonly used antibiotics. A preliminary study of δ-lactone derivatives as new potential candidates for antibacterial drugs was conducted. Particular emphasis was placed on the selection of the structure of lactones with the highest biological activity, especially those with fluorine in their structure as a substituent in terms of action on bacterial lipopolysaccharide (LPS) in the model strains of Escherichia coli K12 (without LPS in its structure) and R2–R4 (LPS of different lengths in its structure). In the presented studies, on the basis of the conducted MIC and MBC tests, it was shown that the antibacterial (toxic) activity of lactones depends on their structure and the length of the bacterial LPS in the membrane of specific strains. Moreover, oxidative damage of bacterial DNA isolated from bacteria after modification with newly synthesized compounds after application of the repair enzyme Fpg glycosylase was analyzed. The analyzed damage values were compared with the modification with appropriate antibiotics: ciprofloxacin, bleomycin, and cloxacillin. The presented research clearly shows that lactone derivatives can be potential candidates as substitutes for drugs, e.g., the analyzed antibiotics. Their chemical and biological activity is related to coumarin derivatives and the corresponding δ-lactone groups in the structure of the substituent. The observed results are of particular importance in the case of increasing bacterial resistance to various drugs and antibiotics, especially in nosocomial infections and neoplasms, and in the era of a microbial pandemic.     

Altered contralateral sensorimotor system organization after experimental hemispherectomy: a structural and functional connectivity study

Hemispherectomy is often followed by remarkable recovery of cognitive and motor functions. This reflects plastic capacities of the remaining hemisphere, involving large-scale structural and functional adaptations. Better understanding of these adaptations may (1) provide new insights in the neuronal configuration and rewiring that underlies sensorimotor outcome restoration, and (2) guide development of rehabilitation strategies to enhance recovery after hemispheric lesioning. We assessed brain structure and function in a hemispherectomy model. With MRI we mapped changes in white matter structural integrity and gray matter functional connectivity in eight hemispherectomized rats, compared with 12 controls. Behavioral testing involved sensorimotor performance scoring. Diffusion tensor imaging and resting-state functional magnetic resonance imaging were acquired 7 and 49 days post surgery. Hemispherectomy caused significant sensorimotor deficits that largely recovered within 2 weeks. During the recovery period, fractional anisotropy was maintained and white matter volume and axial diffusivity increased in the contralateral cerebral peduncle, suggestive of preserved or improved white matter integrity despite overall reduced white matter volume. This was accompanied by functional adaptations in the contralateral sensorimotor network. The observed white matter modifications and reorganization of functional network regions may provide handles for rehabilitation strategies improving functional recovery following large lesions.     

Comparison of frequency and time domain methods of assessment of cerebral autoregulation in traumatic brain injury

The impulse response (IR)-based autoregulation index (ARI) allows for continuous monitoring of cerebral autoregulation using spontaneous fluctuations of arterial blood pressure (ABP) and cerebral flow velocity (FV). We compared three methods of autoregulation assessment in 288 traumatic brain injury (TBI) patients managed in the Neurocritical Care Unit: (1) IR-based ARI; (2) transfer function (TF) phase, gain, and coherence; and (3) mean flow index (Mx). Autoregulation index was calculated using the TF estimation (Welch method) and classified according to the original Tiecks'' model. Mx was calculated as a correlation coefficient between 10-second averages of ABP and FV using a moving 300-second data window. Transfer function phase, gain, and coherence were extracted in the very low frequency (VLF, 0 to 0.05 Hz) and low frequency (LF, 0.05 to 0.15 Hz) bandwidths. We studied the relationship between these parameters and also compared them with patients'' Glasgow outcome score. The calculations were performed using both cerebral perfusion pressure (CPP; suffix ‘c'') as input and ABP (suffix ‘a''). The result showed a significant relationship between ARI and Mx when using either ABP (r=−0.38, P<0.001) or CPP (r=−0.404, P<0.001) as input. Transfer function phase and coherence_a were significantly correlated with ARI_a and ARI_c (P<0.05). Only ARI_a, ARI_c, Mx_a, Mx_c, and phase_c were significantly correlated with patients'' outcome, with Mx_c showing the strongest association.     

Meta-Analysis of the Relationship between TNF-α (−308G/A) and IL-10 (−819C/T) Gene Polymorphisms and Susceptibility to Dengue

Objective: This study determined whether tumor necrosis factor alpha (TNF-α) and Interleukin-10 (IL-10) polymorphisms are associated with susceptibility to dengue.

Methods: a systematic review with meta-analysis was conducted of the associations between the TNF-α (?308G/A) and IL-10 (?819C/T) polymorphisms and dengue.

Results: A total of eight case-controls studies involving 384 individuals with symptomatic dengue, 571 individuals with dengue hemorrhagic fever, and 995 healthy controls were considered in the meta-analysis. There was no significant association between TNF-α (?308G/A) and IL-10 (?819C/T) polymorphism and dengue in overall population. However, stratifying meta-analysis by groups, the meta-analysis revealed association between the TNF-α ?308 G/G (OR: 1.62, CI: 1.02–2.57, p = 0.04) genotype and allele G (OR: 1.62, CI: 1.04–2.55, p = 0.03) that confers susceptibility to symptomatic dengue, while the TNF-α ?308 G/A genotype (OR: 0.69, CI = 0.39–0.99, p = 0.04) and allele A (OR: 0.64, CI: 0.41–1.00, p = 0.05) confers protection to symptomatic dengue. No difference was observed for the TNF-α (?308) and IL-10 (?819C/T) polymorphisms in the comparisons of hemorrhagic dengue versus control and hemorrhagic dengue versus symptomatic dengue.

Conclusion: This meta-analysis showed that TNF-α (?308) polymorphism is associated with dengue symptomatic susceptibility.     

The risk of cholelithiasis in patients after heart transplantation

Introduction

Extended immunosuppressive treatment in patients after heart transplantation modifies etiopathogenesis and occurrence of many diseases in this population. The aim of the present study was to evaluate the frequency and to define risk factors for cholelithiasis after heart transplantation (HTX).

Material and methods

The study population consisted of 176 subjects. Of them, 24 patients (group A) presented with symptomatic cholelithiasis. Another group of 24 patients without cholelithiasis (group B) served as controls. Both groups were similar with respect to age, gender and follow-up after the transplant. Clinical interview, surgical and hospitalization data were collected from medical records.

Results

The groups did not differ in demographic features. There were statistical differences (p < 0.05) between group A and B in rejection reaction, doses of immunosuppressive drugs, type 2 diabetes, serum lipid disorders and acute rejection episodes. These events were caused by modification of treatment, especially the immunosuppressive regimen. Group A consisted of 75% men and 25% women. The frequency of symptomatic cholelithiasis was 11.7% in men and 27.3% in women, on average 19.5%. Mean time to cholelithiasis following HTX was 37.9 ±4.9 (Me = 41.5) months, 27.7 ±8.2 (Me = 30.0) months in women and 41.3 ±5.9 (Me = 41.5) months in men. The female to male ratio was 2.3: 1.

Conclusions

Cholelithiasis following HTX was significantly more frequent as compared with the non-transplant population. Patients with cholelithiasis required more aggressive immunosuppression because of more frequent episodes of acute transplant rejection. Patients with cholelithiasis significantly more frequently showed increased glycemia and blood lipids, which could be the side effect of intensive immunosuppressive therapy.     

Critical closing pressure determined with a model of cerebrovascular impedance

Critical closing pressure (CCP) is the arterial blood pressure (ABP) at which brain vessels collapse and cerebral blood flow (CBF) ceases. Using the concept of impedance to CBF, CCP can be expressed with brain-monitoring parameters: cerebral perfusion pressure (CPP), ABP, blood flow velocity (FV), and heart rate. The novel multiparameter method (CCPm) was compared with traditional transcranial Doppler (TCD) calculations of CCP (CCP1). Digital recordings of ABP, intracranial pressure (ICP), and TCD-based FV from previously published studies of 29 New Zealand White rabbits were reanalyzed. Overall, CCP1 and CCPm showed correlation across wide ranges of ABP, ICP, and PaCO2 (R=0.93, P<0.001). Three physiological perturbations were studied: increase in ICP (n=29) causing both CCP1 and CCPm to increase (P<0.001 for both); reduction of ABP (n=10) resulting in decrease of CCP1 (P=0.006) and CCPm (P=0.002); and controlled increase of PaCO2 (n=8) to hypercapnic levels, which decreased CCP1 and CCPm, albeit insignificantly (P=0.123 and P=0.306 respectively), caused by a spontaneous significant increase in ABP (P=0.025). Multiparameter mathematical model of critical closing pressure explains the relationship of CCP on brain-monitoring variables, allowing the estimation of CCP during cases such as hypercapnia-induced hyperemia, where traditional calculations, like CCP1, often reach negative non-physiological values.     

Drainage of pleural effusions in the course of unrecognised constrictive pericarditis: a cause of severe haemodynamic deterioration

Constrictive pericarditis (CP) is a rare disease which can be easily overlooked in the absence of typical pericardial calcification. One of its most frequent manifestations is pleural effusion. We present a case report of a patient with unrecognised CP in whom plerocentesis led to haemodynamic collapse, and we speculate about the potential pathomechanism. No obvious criterion of CP or severe systolic dysfunction was found in baseline echocardiography. We consider that patients with advanced CP are remarkably prone to haemodynamic decompensation secondary to pleural drain.     

Breast implant infections

Infection after breast implant surgery occurs in 1.1% to 2.5% of procedures performed for augmentation and up to 35% of procedures performed for reconstruction after mastectomy. Most infections result from skin organisms and occur in the immediate postoperative period, although infections can occasionally present after many years. Diagnosis of breast implant infection relies on the clinical presentation of breast pain, swelling, erythema, and drainage in conjunction with ultrasound-guided cultures of periprosthetic fluid. Management commonly involves implant removal, with device salvage attempted in select situations.