Opioids and renal function.

Opioids, both endogenous and exogenous, have a strong influence on the renal function through different mechanisms, producing changes in the renal excretion of water and sodium. Several studies have demonstrated that opioids influence renal function, according to the agonist profile used. Mu, kappa, and delta agonists produce different renal effects, although the mechanisms remain unclear. Experimental data have given the input for a possible therapeutic role of kappa agonists for some specific conditions, for example, in treating water retention or hyponatremia occurring in patients who have hepatic cirrhosis with ascites. On the other hand, changes in renal function might strongly condition the use of opioids in the clinical setting, and the knowledge of the relationship between opioids and renal function is mandatory for a tailored approach to accommodate the individual responses in terms of pain intensity, tolerance, and adverse effects experienced by these groups of patients. The influence of renal function when using different opioids in the clinical setting is reviewed, as well as problems related to transplantation, renal damage induced by opioid addiction, and problems related to the use of opioid antagonists in such conditions. PERSPECTIVE: Endogenous opioids exert physiologic effects on renal function, and the use of opioids may have an influence on renal activity. Renal impairment has a serious impact on the clearance of most opioids used in the clinical setting. Biochemical and clinical monitoring is mandatory to prevent serious complications.     

Bone marrow derived stem cells in joint and bone diseases: a concise review

Stem cells have huge applications in the field of tissue engineering and regenerative medicine. Their use is currently not restricted to the life-threatening diseases but also extended to disorders involving the structural tissues, which may not jeopardize the patients’ life, but certainly influence their quality of life. In fact, a particularly popular line of research is represented by the regeneration of bone and cartilage tissues to treat various orthopaedic disorders. Most of these pioneering research lines that aim to create new treatments for diseases that currently have limited therapies are still in the bench of the researchers. However, in recent years, several clinical trials have been started with satisfactory and encouraging results. This article aims to review the concept of stem cells and their characterization in terms of site of residence, differentiation potential and therapeutic prospective. In fact, while only the bone marrow was initially considered as a “reservoir” of this cell population, later, adipose tissue and muscle tissue have provided a considerable amount of cells available for multiple differentiation. In reality, recently, the so-called “stem cell niche” was identified as the perivascular space, recognizing these cells as almost ubiquitous. In the field of bone and joint diseases, their potential to differentiate into multiple cell lines makes their application ideally immediate through three main modalities: (1) cells selected by withdrawal from bone marrow, subsequent culture in the laboratory, and ultimately transplant at the site of injury; (2) bone marrow aspirate, concentrated and directly implanted into the injury site; (3) systemic mobilization of stem cells and other bone marrow precursors by the use of growth factors. The use of this cell population in joint and bone disease will be addressed and discussed, analysing both the clinical outcomes but also the basic research background, which has justified their use for the treatment of bone, cartilage and meniscus tissues.     

Changes in the prescribing pattern of antidepressant drugs in elderly patients: an Italian,nationwide, population-based study

Background

Despite the high use of antidepressants (ADs) among the elderly, there is limited information about the prescribing pattern of these drugs in the Italian elderly population. The aim of this study was to analyze the trend in the use of ADs in the Italian elderly patients in the years 2003-2009, and specifically, to evaluate rates and predictors of AD treatment discontinuation in depressed older patients.

Methods

The nationwide general practice Health Search Database (HSD) was used to identify AD users aged 65 years old and over from 2003 to 2009. ADs were categorized as (1) selective serotonin reuptake inhibitors (SSRIs); (2) serotonin-norepinephrine reuptake inhibitors (SNRIs); (3) tricyclic antidepressants (TCAs); (4) noradrenergic and specific serotonergic antidepressants (NaSSAs); and (5) other ADs. Incidence and prevalence of AD use per 1,000 inhabitants was calculated by drug class and single compound. We also measured rates and predictors of AD discontinuation (i.e., treatment gap?≥?60 days) during the first year of therapy.

Results

Overall, 39,557 AD users ≥65 years (17 % of the total HSD elderly population) were included in the study. SSRIs were increasingly and most frequently prescribed ADs (102.7-195.3 per 1,000 over seven years). The most common indications for AD use were depression and anxiety. Overall, 14 % of AD users continued their AD medication without treatment gaps, 27 % were intermittent AD users and 58 % discontinued their ADs during the first year of follow-up. Specific AD classes such as TCAs and ‘other ADs were found to be predictors of discontinuation. In depressed patients, the use of NaSSas, TCAs and ‘other ADs as well the concomitant use of >5 drugs (other than ADs) and living in Southern Italy were more likely to predict discontinuation.

Conclusion

ADs, especially SSRIs, are widely and increasingly prescribed in elderly Italian patients in recent years. The observed high AD discontinuation rates are likely to impact the achievement of a therapeutic endpoint in depressed patients. Patients who are at high risk of AD discontinuation such as those receiving multi-drug therapy or living in Southern Italy should be monitored more closely to improve benefits of AD treatments.     

Decoding ultrafast polarization responses in lead halide perovskites by the two-dimensional optical Kerr effect

The ultrafast polarization response to incident light and ensuing exciton/carrier generation are essential to outstanding optoelectronic properties of lead halide perovskites (LHPs). A large number of mechanistic studies in the LHP field to date have focused on contributions to polarizability from organic cations and the highly polarizable inorganic lattice. For a comprehensive understanding of the ultrafast polarization response, we must additionally account for the nearly instantaneous hyperpolarizability response to the propagating light field itself. While light propagation is pivotal to optoelectronics and photonics, little is known about this in LHPs in the vicinity of the bandgap where stimulated emission, polariton condensation, superfluorescence, and photon recycling may take place. Here we develop two-dimensional optical Kerr effect (2D-OKE) spectroscopy to energetically dissect broadband light propagation and dispersive nonlinear polarization responses in LHPs. In contrast to earlier interpretations, the below-bandgap OKE responses in both hybrid CH₃NH₃PbBr₃ and all-inorganic CsPbBr₃ perovskites are found to originate from strong hyperpolarizability and highly anisotropic dispersions. In both materials, the nonlinear mixing of anisotropically propagating light fields results in convoluted oscillatory polarization dynamics. Based on a four-wave mixing model, we quantitatively derive dispersion anisotropies, reproduce 2D-OKE frequency correlations, and establish polarization-dressed light propagation in single-crystal LHPs. Moreover, our findings highlight the importance of distinguishing the often-neglected anisotropic light propagation from underlying coherent quasiparticle responses in various forms of ultrafast spectroscopy.

Understanding the ultrafast polarization response to light fields and the subsequent generation of charge carriers or excitons is key to establishing the photophysical mechanisms in the excellent optoelectronic material system of lead halide perovskites (LHPs) (1). The two ionic polarization contributions by the reorientational motion of organic cations and the deformation of the inorganic cages have been discussed within dynamic screening models (2–4) and large polaron formation (5), respectively and jointly, whereas the immediate electronic polarization response to the light field itself has been neglected so far. In many optoelectronic applications, nevertheless, not only charge carrier transport but also light propagation right below the bandgap is essential. In LHP nanowire lasers, the lasing modes are known to be redshifted from excitonic resonances due to efficient coupling to plasmon emission (6). In LHP-based exciton–polariton devices, light–matter coupling redshifts the hybrid state on the lower polariton branch (7). Propagation of subgap light is known to boost the efficiency of LHP photovoltaic cells and light-emitting devices by the so-called “photon recycling” (8). Light propagation strongly influences the function of LHP photonic devices in general (9, 10). A key feature of light propagation near the bandgap is its strong photon energy dependence, as is obvious from the classic Lorentzian model for the dielectric function near an optical resonance (11). However, most photophysical experiments probing carrier/exciton formation, screening, scattering, and nonlinear optical responses employ ultrashort excitation pulses with inherently broad energy distribution and thus convoluted spectral responses. Here, we develop a Fourier-transform-based laser spectroscopy technique, two-dimensional optical Kerr effect (2D-OKE), to investigate light propagation and nonlinear polarization responses directly in the time domain with superior excitation energy resolution near the electronic bandgap.The third-order nonlinear electric polarization P(3) serves as an in situ probe of a material’s polarizability and governs the ultrafast macroscopic response to an incident light field. This is employed in a variety of spectroscopies, such as (magneto-) OKE (12, 13), coherent phonon spectroscopy (14, 15), and four-wave mixing (FWM) in general (11). Recently, OKE has been applied to LHP single crystals: Below the bandgap, the dominating nonoscillatory Kerr response of MAPbBr₃ (MA = CH₃NH₃) compared to its all-inorganic counterpart CsPbBr3 was previously attributed to the transient polarization anisotropy caused by liquidlike reorientation dynamics of organic cations (2) and lattice disorder (5). The exponentially decaying responses with above-gap excitations were discussed in relation to polaron formation in both materials (5). Interestingly, for excitation energies close to the bandgap in CsPbBr₃ at room temperature, time-resolved OKE reveals complex oscillatory features. Such oscillatory transient birefringence signals are usually attributed to coherently excited collective modes, such as phonons (15–17) or magnons (18, 19), but the strong dependence of the oscillatory frequency on pump-photon energy in OKE seems to contradict these origins in LHPs (5). In this work, we unveil a unified source for the Kerr responses in single-crystal LHPs by tracing contributions from hyperpolarizability and the peculiar light propagation close to electronic transitions.     

Does age influence the success of intra-tympanic steroid treatment in idiopathic sudden deafness?

Conclusions: The present study shows that AGE, DELAY, and PTA_PRE may be considered factors influencing therapeutic success in intra-tympanic steroid therapy. Objective: The aim of the study is to evaluate the relationship between the therapeutic success of intra-tympanic prednisolone therapy and age, in patients affected by idiopathic sudden sensorineural hearing loss (ISSNHL), considering the influence of factors such as delay, gender, and pure tone average (PTA) pre-therapy. Method: This retrospective study involved 402 consecutive patients, affected by unilateral ISSNHL between January 2009 and January 2014. Patients were divided into two groups based on age: group one with 94 patients aged over 65 years and group two with all 402 patients enrolled in the study, including those over 65. Results: PTA recorded before the beginning of the therapy (PTA_PRE) in group one was worse than for group two. In both groups the therapy was significantly effective in improving hearing thresholds, even if PTA_PRE was significant and negatively correlated with success rate. This effect disappeared within the population over 65. On average, each day of DELAY from the onset of hearing loss to the beginning of therapy cuts almost 2% of the possibility to recover. AGE was negative and significant when specified continuously for group two.     

Is there a practical way of predicting therapeutic success in type 2 diabetes on the basis of psychological features? Development and validation of the Psychological Predictors of Therapeutic success in Diabetes (PPTD) questionnaire

Many psychiatric disorders and symptoms have been associated with impaired metabolic control in type 2 diabetes; several studies focused on non-pathological psychological features. Aims of this observational, longitudinal study are: the assessment of the impact of a wide range of psychological factors on metabolic control in type 2 diabetes; and the development and validation of a simple questionnaire to assess the impact of psychological factors on therapeutic success. To identify psychological factors interfering with attainment of glycemic targets, a prospective 1-year study was performed on a sample of 250 patients with type 2 diabetes. The impact of identified factors on therapeutic outcome was then subsequently verified on a further, independent sample of 200 patients. The first phase of the study allowed the development of a 19-items questionnaire, the Psychological Predictors of Therapeutic success in Diabetes (PPTD) questionnaire. Validation analyses showed that the questionnaire was able to predict therapeutic success. Patients with HbA1c ≤7 % (53 mmol/mol) at follow-up showed higher test scores than those with HbA1c >7 % [31.0 (26.2; 35.0) vs 28.0 (23.0; 32.0); p = 0.016]. The attainment and maintenance of therapeutic goals in patients with type 2 diabetes depend on a wide range of factors. The PPTD is an attempt at condensing the complexity of psychological factors affecting glycemic control in a simple and easy-to-use self-reported questionnaire, which can be used in wide-scale research.