Multifunctional cationic surfactants with a labile amide linker as efficient antifungal agents-mechanisms of action.

Our research aimed to expand the knowledge of relationships between the structure of multifunctional cationic dicephalic surfactants with a labile linker-N,N-bis[3,3-(dimethylamine)propyl]alkylamide dihydrochlorides and N,N-bis[3,3-(trimethylammonio)propyl]alkylamide dibromides (alkyl: n-C9H19, n-C11H23, n-C13H27, n-C15H31)-and their possible mechanism of action on fungal cells using the model organism Saccharomyces cerevisiae. General studies performed on surfactants suggest that in most cases, their main mechanism of action is based on perforation of the cell membranes and cell disruption. Experiments carried out in this work with cationic dicephalic surfactants seem to modify our understanding of this issue. It was found that the investigated compounds did not cause perforation of the cell membrane and could only interact with it, increasing its permeability. The surfactants tested can probably penetrate inside the cells, causing numerous morphological changes, and contribute to disorders in the lipid metabolism of the cell resulting in the formation of lipid droplet aggregates. This research also showed that the compounds cause severe oxidative stress within the cells studied, including increased production of superoxide anion radicals and mitochondrial oxidative stress. Dicephalic cationic surfactants due to their biodegradability do not accumulate in the environment and in the future may be used as effective antifungal compounds in industry as well as medicine, which will be environmentally friendly. KEY POINTS: • Dicephalic cationic surfactants do not induce disruption of the cell membrane. • Surfactants could infiltrate into the cells and cause accumulation of lipids. • Surfactants could cause acute oxidative stress in yeast cells. • Compounds present multimodal mechanism of action. Graphical abstract.

Impact of the COVID-19 pandemic on hospitalizations for acute coronary syndromes: a multinational study.

BACKGROUND: COVID-19 has challenged the health system organization requiring a fast reorganization of diagnostic/therapeutic pathways for patients affected by time-dependent diseases such as acute coronary syndromes (ACS). AIM: To describe ACS hospitalizations, management, and complication rate before and after the COVID-19 pandemic was declared. DESIGN: Ecological retrospective study. Methods: We analyzed aggregated epidemiological data of all patients > 18 years old admitted for ACS in twenty-nine hub cardiac centers from 17 Countries across 4 continents, from December 1st, 2019 to April 15th, 2020. Data from December 2018 to April 2019 were used as historical period. RESULTS: A significant overall trend for reduction in the weekly number of ACS hospitalizations was observed (20.2%; 95% confidence interval CI [1.6, 35.4] P = 0.04). The incidence rate reached a 54% reduction during the second week of April (incidence rate ratio: 0.46, 95% CI [0.36, 0.58]) and was also significant when compared to the same months in 2019 (March and April, respectively IRR: 0.56, 95%CI [0.48, 0.67]; IRR: 0.43, 95%CI [0.32, 0.58] p < 0.001). A significant increase in door-to-balloon, door-to-needle, and total ischemic time (p <0.04 for all) in STEMI patents were reported during pandemic period. Finally, the proportion of patients with mechanical complications was higher (1.98% vs. 0.98%; P = 0.006) whereas GRACE risk score was not different. CONCLUSIONS: Our results confirm that COVID-19 pandemic was associated with a significant decrease in ACS hospitalizations rate, an increase in total ischemic time and a higher rate of mechanical complications on a international scale.

Antifungal activity of newly synthesized chemodegradable dicephalic-type cationic surfactants.

The studies were aimed to contribute to the elucidation of the relationships between structure of the double-headed cationic surfactants - N,N-bis[3,3'-(dimethylamine)propyl]alkylamide dihydrochlorides and N,N-bis[3,3'-(trimethylammonio)propyl]alkylamide dibromides (alkyl: n-C9H19, n-C11H23, n-C13H27, n-C15H31), which are of particular interest, as they contain a labile amide group in the molecule and their antifungal activity. Therefore, the minimal inhibitory and fungicidal concentrations (MIC and MFC) of dicephalic surfactants against various fungi were tested using standardized methods. Most of the tested fungi were resistant to the Cn(TAPABr)2 compounds. The strongest growth inhibition was caused by Cn(DAPACl)2 series, which MICs ranged from 6.5 to 16 µM. The influence of dicephalic surfactants on Candida albicans biofilm and adhesion to the various surfaces was investigated with crystal violet staining or colony counting. The reduction of fungal adhesion was also observed, especially to the glass surface. One of the compounds (C14(DAPACl)2) caused DNA leakage from C. albicans cells. Further studies showed the impact of dicephalic surfactants on ROS production, accumulation of lipid droplets and filament formation. This study points to the possibility of application of dicephalic surfactants as the surface-coating agents to prevent biofilm formation or as disinfectants. The results give an insight into the possible mechanism of action of newly synthesized dicephalic surfactants in yeast cells.

Polymeric nanocapsules with up-converting nanocrystals cargo make ideal fluorescent bioprobes.

An innovative approach for up-converting nanoparticles adaptation for bio-related and theranostic applications is presented. We have successfully encapsulated multiple, ~8 nm in size NaYF4 nanoparticles inside the polymeric nanocarriers with average size of ~150 nm. The initial coating of nanoparticles surfaces was preserved due to the hydrophobic environment inside the nanocapsules, and thus no single nanoparticle surface functionalization was necessary. The selection of biodegradable and sugar-based polyelectrolyte shells ensured biocompatibility of the nanostructures, while the choice of Tm(3+) and Yb(3+) NaYF4 nanoparticles co-doping allowed for near-infrared to near-infrared bioimaging of healthy and cancerous cell lines. The protective role of organic shell resulted in not only preserved high up-converted emission intensity and long luminescence lifetimes, without quenching from water environment, but also ensured low cytotoxicity and high cellular uptake of the engineered nanocapsules. The multifunctionality of the proposed nanocarriers is a consequence of both the organic exterior part that is accessible for conjugation with biologically important molecules, and the hydrophobic interior, which in future application may be used as a container for co-encapsulation of inorganic nanoparticles and anticancer drug cargo.

Biofilm prevention by dicephalic cationic surfactants and their interactions with DNA.

AIMS: The studies were aimed to contribute to the elucidation of the relationships between structure of the double-headed cationic surfactants-N,N-bis[3,3'-(dimethylamine)- propyl]alkylamide dihydrochlorides and N,N-bis[3,3'-(trimethylammonio)propyl]alkylamide dibromides (alkyl: n-C9 H19 , n-C11 H23 , n-C13 H27 , n-C15 H31 ) and their antibacterial and biofilm preventing activity. METHODS AND RESULTS: The minimal inhibitory and bactericidal concentrations (MIC and MBC) of dicephalic surfactants against Staphylococcus epidermidis and Pseudomonas aeruginosa were tested using standard methods. Pseudomonas aeruginosa was resistant to studied compounds but MBC values against Staph. epidermidis reached 0·48-0·01 mmol l(-1) . The influence of dicephalic surfactants on bacterial biofilm and adhesion to the various surfaces was investigated with crystal violet staining or colony counting. The reduction in bacterial adhesion was observed, especially in the case of glass and stainless steel. The condensation of the DNA was shown in the ethidium bromide intercalation assay. CONCLUSIONS: Dicephalic surfactants exhibited antibacterial activity against Staph. epidermidis. The activity of studied compounds depended on the hydrocarbon chain length and the counterion. Surfactants deposited on different materials reduced Staph. epidermidis adhesion, dependently on the surfactant structure and the substratum. Dicephalic surfactants showed the ability of DNA compaction. SIGNIFICANCE AND IMPACT OF THE STUDY: This study points the possibility of application of dicephalic surfactants as the surface-coating agents to prevent biofilm formation. These compounds efficiently condensed DNA and are potential candidates for further studies towards the transfection.

Disentangling Electronic and Vibrational Coherence in the Phycocyanin-645 Light-Harvesting Complex.

Energy transfer between chromophores in photosynthesis proceeds with near-unity quantum efficiency. Understanding the precise mechanisms of these processes is made difficult by the complexity of the electronic structure and interactions with different vibrational modes. Two-dimensional spectroscopy has helped resolve some of the ambiguities and identified quantum effects that may be important for highly efficient energy transfer. Many questions remain, however, including whether the coherences observed are electronic and/or vibrational in nature and what role they play. We utilize a two-color, four-wave mixing experiment with control of the wavelength and polarization to selectively excite specific coherence pathways. For the light-harvesting complex PC645, from cryptophyte algae, we reveal and identify specific contributions from both electronic and vibrational coherences and determine an excited-state structure based on two strongly coupled electronic states and two vibrational modes. Separation of the coherence pathways also uncovers the complex evolution of these coherences and the states involved.

Capillary rise dynamics of aqueous glycerol solutions in glass capillaries: a critical examination of the Washburn equation.

The classic description of capillary rise given by the Washburn equation was recently questioned in the light of experimental evidence for a velocity dependent dynamic contact angle at a moving contact line. We present a systematic investigation of the capillary rise dynamics of glycerol and aqueous glycerol solutions in vertical glass capillaries of various radii. For pure glycerol, the results of our experiments are in almost perfect agreement with the predictions of the Washburn equation using independently measured values for the liquid and capillary parameters. For aqueous glycerol solutions we observe discrepancies between the theoretical expectations and the experimental results, which are increasing with the water content of the solution. A thorough analysis, combined with scaling arguments, allows us to conclude that dynamic contact angle effects alone cannot provide a consistent explanation for these discrepancies. Rather, they can be perfectly accounted for if the mixture flowing in the capillary would have an effective, increased viscosity (in respect to the nominal value). We suggest and briefly discuss various mechanisms that could contribute to this observed behavior.

Coherent Vibronic Coupling in Light-Harvesting Complexes from Photosynthetic Marine Algae.

Observations of long-lived coherences in photosynthetic light-harvesting complexes utilize short pulses with broad spectral bandwidths to coherently excite multiple transitions and coherent superpositions. In order to identify the role that such quantum effects might play in efficient energy transfer, however, an alternative approach is required. We have developed a technique for two-color photon echo spectroscopy to selectively excite the pathway of interest and measure its evolution in the absence of any other excitation. We use this technique to excite a coherence pathway in phycocyanin-645 from cryptophyte algae and measure the dynamics of this coherence. A decoherence time of 500 fs was measured, and clear signatures for strong coupling between the electronic states and phonon modes were observed, allowing coherent coupling between otherwise nonresonant transitions. This provides detailed experimental evidence of the long-lived coherences and the nature of the quantum mechanical interactions between electronic states and phonon modes in phycocyanin-645 from cryptophyte marine algae.

The influence of bronchial asthma on sexual maturation of girls.

The aim of this study was to evaluate the effect of bronchial asthma on sexual maturation of girls. The study encompassed 111 girls aged 8-17 years (58 girls treated for bronchial asthma and 53 healthy girls). The assessment of girls' sexual maturation has been performed using the Tanner-Marshall scale, determining stages of the development of secondary gender characters - mammary gland (Thelarche: Th1 - Th5), public hair (Pubarche: P1-P5), axillary hair (Adrenarche: A1-A4) and menarche age. The first symptoms of puberty among asthmatic girls started at 11.83+/-2.37 (Th2) and 12.85+/-1.87 (P2) years; they achieved the last stadium, on average, at 15 (Th5) and 17 (P5) years. The ages of Th2 and P2 were comparable, but the ages of Th4 and P5 were statistically younger in healthy girls. Asthmatic girls started to menstruate earlier (10.84+/-1.93 years) than controls (12.24+/-1.16 years). We conclude that bronchial asthma does not affect the beginning of sexual maturation, but it delays the final stage of secondary sexual characters' development. The age at menarche is accelerated in bronchial asthma and it depends on asthma severity and its clinical control.

The influence of bronchial asthma on menstrual cycle.

The aim of this study was to evaluate the effect of bronchial asthma on menstrual cycle. The study population consisted of 111 girls aged 8-17 years (58 girls with bronchial asthma and 53 healthy girls) of the mean age of 13.17+/-2.74 years. The age at menarche and menstrual cycle parameters were analyzed. Asthmatic girls started to menstruate earlier than healthy girls (P=0.0004). The severity of bronchial asthma (P=0.0096) correlated with the age at menarche. Irregular menstrual cycles were found in 50.0% of asthmatic girls and 27.8% of control group (P=0.03). Algomenorrhea was observed in 68.0% of girls with asthma and in 80.6% of healthy ones (P=0.013). We conclude that bronchial asthma increases the risk of irregular menstrual cycles prevalence but decreases the frequency of algomenorrhea among girls. The age at menarche is accelerated in bronchial asthma.

[Medical management of patients with benign paroxysmal positional vertigo]. / Zur ärztlichen Versorgung von Patienten mit benignem paroxysmalen Lagerungsschwindel.

Benign paroxysmal positional vertigo (BPPV) is the most common vestibular disorder which can be simply diagnosed. The evolution of highly effective positioning maneuvers has made BPPV the most successfully treatable cause of vertigo. We evaluated patients with BPPV with regard to past medical history and disease-related diagnostic and therapeutic procedures. Forty-two patients were recruited from a specialised dizziness clinic, and a further 29 patients were recruited from a neurological practice. The mean duration of the disease was 3.2 years, with an average of 2.4 episodes lasting typically several weeks to months. More than half of the patients felt severely disabled by BPPV. On average, three different medical specialities were consulted. Cerebral imaging (42%), caloric testing (46%), and audiometry (49%) were performed more often than diagnostic positioning (28%). Most patients received ineffective or no therapy, and only 4% were treated with a specific therapeutic positioning maneuver. Benign paroxysmal positional vertigo is a long-lasting and frequently recurrent disease which leads to significant morbidity and medical costs. The recent progress in the diagnosis and therapy of BPPV has not yet been widely established in medical practice in Germany.

Operative treatment of ulnar collateral ligament injuries of the elbow in athletes.

Over a 6-year period, the senior author (JRA) performed 91 ulnar collateral ligament reconstructions (N = 78) or repairs (N = 13). All patients were male and between the ages of 15 and 39 years (average, 21.6). Thirty-seven patients (41%) were professional baseball players, 41 (45%) were collegiate baseball players, and 7 (7.7%) were high school or recreational players. Subcutaneous ulnar nerve transposition with stabilization of the nerve with fascial slings of the flexor pronator mass was performed in all patients, and additional procedures were performed in 27 patients (29.7%), including 22 excisions of posteromedial olecranon osteophytes. Average follow-up was 35.4 months. Ten patients had preoperative ulnar nerve symptoms, nine of whom had complete resolution of symptoms after surgery. Complications occurred in eight patients. The average time from surgery to initiation of the interval throwing program was 3.4 months, and the average time to return to competitive throwing was 9.8 months. Sixty-seven patients (74%) were available for follow-up; of these, 53 (79%) had returned to their previous levels of competition or to a higher level. Reconstruction of the ulnar collateral ligament, with transposition and stabilization of the ulnar nerve and appropriate rehabilitation, was found to be effective in correcting medial instability of the elbow and allowed most athletes to return to previous levels of play in less than 1 year.

Evolution of a light-harvesting protein by addition of new subunits and rearrangement of conserved elements: crystal structure of a cryptophyte phycoerythrin at 1.63-A resolution.

Cryptophytes are unicellular photosynthetic algae that use a lumenally located light-harvesting system, which is distinct from the phycobilisome structure found in cyanobacteria and red algae. One of the key components of this system is water-soluble phycoerythrin (PE) 545 whose expression is enhanced by low light levels. The crystal structure of the heterodimeric alpha(1)alpha(2)betabeta PE 545 from the marine cryptophyte Rhodomonas CS24 has been determined at 1.63-A resolution. Although the beta-chain structure is similar to the alpha and beta chains of other known phycobiliproteins, the overall structure of PE 545 is novel with the alpha chains forming a simple extended fold with an antiparallel beta-ribbon followed by an alpha-helix. The two doubly linked beta50/beta61 chromophores (one on each beta subunit) are in van der Waals contact, suggesting that exciton-coupling mechanisms may alter their spectral properties. Each alpha subunit carries a covalently linked 15,16-dihydrobiliverdin chromophore that is likely to be the final energy acceptor. The architecture of the heterodimer suggests that PE 545 may dock to an acceptor protein via a deep cleft and that energy may be transferred via this intermediary protein to the reaction center.

Symptomatic thrower's exostosis. Arthroscopic evaluation and treatment.

A long-term follow-up was performed on 22 patients treated for a posterior glenoid osteophyte and symptomatic posterior shoulder pain during either the late cocking, acceleration, or follow-through phases of throwing. Arthroscopic evaluation of these patients revealed undersurface tearing of the rotator cuff in all but one. Fifteen patients also had tearing of the posterior labrum. Anterior labral fraying was noted in four patients. Treatment consisted of debridement of the rotator cuff and labral tears. The posterior glenoid osteophyte was removed arthroscopically in 11 patients. Eighteen of 22 throwers treated were available for long-term follow-up at a mean of 6.3 years (range, 1 to 12). Only 10 of 18 (55%) throwers evaluated had returned to their premorbid level of throwing. All 10 were asymptomatic and had maintained a high level of performance for a mean of 3.6 years (range, 1 to 8). At the time of latest follow-up, five players were still participating at the major league level and five had retired. One patient had recurrence of the exostosis 8 years after surgery. Among our patients a trend existed toward a poorer result and failure of return to activity with a posterior osteophyte greater than 100 mm2. A posterior glenoid exostosis, when identified in the symptomatic shoulder of the throwing athlete, can be considered a definite marker of internal impingement.

Rehabilitation after anterior cruciate ligament reconstruction in the female athlete.

OBJECTIVE: To discuss the rehabilitation program after anterior cruciate ligament (ACL) reconstruction in the female athlete. In addition, we will discuss 8 unique characteristics identified in the female athlete and specific training drills to address and correct the potentially deleterious effects of these unique characteristics. BACKGROUND: The female athlete appears to be more susceptible to noncontact ACL injuries than the male athlete. There seem to be many differences between the female and male athlete that may contribute to the increased injury rate in the female athlete. These variations include anatomical and neuromuscular considerations and differences. DESCRIPTION: Based on the unique characteristics of the female athlete and the anatomical and neuromuscular dissimilarities, a specially designed rehabilitation program has been established for the female athlete after ACL surgery. CLINICAL ADVANTAGES: The rehabilitation drills discussed in this article challenge the neuromuscular system through proprioception, kinesthesia, dynamic joint stability, neuromuscular control, and perturbation training activities. Improving the female athlete's neuromuscular system will, we believe, expedite the injured athlete's recovery after ACL injury or surgery. Although the concepts discussed are part of a postoperative rehabilitation program after ACL surgery, these concepts may also be implemented as a preventive program to assist in reducing the incidence of ACL injuries in the female athlete.

Patellofemoral disorders: a classification system and clinical guidelines for nonoperative rehabilitation.

Patellofemoral disorders are among the most common clinical conditions managed in the orthopaedic and sports medicine setting. Nonoperative intervention is typically the initial form of treatment for patellofemoral disorders; however, there is no consensus on the most effective method of treatment. Although numerous treatment options exist for patellofemoral patients, the indications and contraindications of each approach have not been well established. Additionally, there is no generally accepted classification scheme for patellofemoral disorders. In this paper, we will discuss a classification system to be used as the foundation for developing treatment strategies and interventions in the nonsurgical management of patients with patellofemoral pain and/or dysfunction. The classification system divides the patellofemoral disorders into eight groups, including: 1) patellar compression syndromes, 2) patellar instability, 3) biomechanical dysfunction, 4) direct patellar trauma, 5) soft tissue lesions, 6) overuse syndromes, 7) osteochondritis diseases, and 8) neurologic disorders. Treatment suggestions for each of the eight patellofemoral dysfunction categories will be briefly discussed.

Biomechanics of the knee during closed kinetic chain and open kinetic chain exercises.

PURPOSE: Although closed (CKCE) and open (OKCE) kinetic chain exercises are used in athletic training and clinical environments, few studies have compared knee joint biomechanics while these exercises are performed dynamically. The purpose of this study was to quantify knee forces and muscle activity in CKCE (squat and leg press) and OKCE (knee extension). METHODS: Ten male subjects performed three repetitions of each exercise at their 12-repetition maximum. Kinematic, kinetic, and electromyographic data were calculated using video cameras (60 Hz), force transducers (960 Hz), and EMG (960 Hz). Mathematical muscle modeling and optimization techniques were employed to estimate internal muscle forces. RESULTS: Overall, the squat generated approximately twice as much hamstring activity as the leg press and knee extensions. Quadriceps muscle activity was greatest in CKCE when the knee was near full flexion and in OKCE when the knee was near full extension. OKCE produced more rectus femoris activity while CKCE produced more vasti muscle activity. Tibiofemoral compressive force was greatest in CKCE near full flexion and in OKCE near full extension. Peak tension in the posterior cruciate ligament was approximately twice as great in CKCE, and increased with knee flexion. Tension in the anterior cruciate ligament was present only in OKCE, and occurred near full extension. Patellofemoral compressive force was greatest in CKCE near full flexion and in the mid-range of the knee extending phase in OKCE. CONCLUSION: An understanding of these results can help in choosing appropriate exercises for rehabilitation and training.

Current concepts: the stabilizing structures of the glenohumeral joint.

Significant contemporary advances have permitted a more comprehensive understanding and development of some interesting concepts about the glenohumeral joint. The purpose of this review paper was to discuss current concepts related to the anatomic stabilizing structures of the shoulder joint complex and their clinical relevance to shoulder instability. The clinical syndrome of shoulder instability represents a wide spectrum of symptoms and signs which may produce various levels of dysfunction, from subtle subluxations to gross joint instability. The glenohumeral joint attains functional stability through a delicate and intricate interaction between the passive and active stabilizing structures. The passive constraints include the bony geometry, glenoid labrum, and the glenohumeral joint capsuloligamentous structures. Conversely, the active constraints, also referred to as the active mechanisms, include the shoulder complex musculature, the proprioceptive system, and the musculoligamentous relationship. The interaction of the active and passive mechanisms which provide passive and active glenohumeral joint stability will be thoroughly discussed in this paper.

The physical examination of the glenohumeral joint: emphasis on the stabilizing structures.

Thorough descriptions of specific physical examination tests used to determine glenohumeral instability are lacking in the scientific literature. The purpose of this paper was to discuss the importance of the subjective history and illustrate the physical examination of the glenohumeral joint. Additionally, the authors will illustrate specific stability assessment for the glenohumeral joint based on current basic science and clinical research. The physical examination of a patient whose history suggests subtle glenohumeral joint instability may be extremely difficult for the clinician due to the normal amount of capsular laxity commonly present in most individuals. An essential component of the physical examination is a through and meticulous subjective history which includes the mechanisms of injury and/or dysfunction, chief complaint, level of disability, and aggravating movements. The physical examination must include an assessment of motion, static stability testing, muscle testing, and a neurologic assessment. A comprehensive understanding of various stability testing maneuvers is important for the clinician to appreciate. The evaluation techniques discussed in this paper should assist the clinician in determining the passive stability of the glenohumeral joint.