Acute and chronic effects of Titanium dioxide (TiO2) PM1 on honey bee gut microbiota under laboratory conditions.

Apis mellifera is an important provider of ecosystem services, and during flight and foraging behaviour is exposed to environmental pollutants including airborne particulate matter (PM). While exposure to insecticides, antibiotics, and herbicides may compromise bee health through alterations of the gut microbial community, no data are available on the impacts of PM on the bee microbiota. Here we tested the effects of ultrapure Titanium dioxide (TiO2) submicrometric PM (i.e., PM1, less than 1 µm in diameter) on the gut microbiota of adult bees. TiO2 PM1 is widely used as a filler and whitening agent in a range of manufactured objects, and ultrapure TiO2 PM1 is also a common food additive, even if it has been classified by the International Agency for Research on Cancer (IARC) as a possible human carcinogen in Group 2B. Due to its ubiquitous use, honey bees may be severely exposed to TiO2 ingestion through contaminated honey and pollen. Here, we demonstrated that acute and chronic oral administration of ultrapure TiO2 PM1 to adult bees alters the bee microbial community; therefore, airborne PM may represent a further risk factor for the honey bee health, promoting sublethal effects against the gut microbiota.

Relationship between sugarcane culm and leaf biomass composition and saccharification efficiency.

BACKGROUND: Lignocellulosic biomass is recognized as a promising renewable feedstock for the production of biofuels. However, current methods for converting biomass into fermentable sugars are considered too expensive and inefficient due to the recalcitrance of the secondary cell wall. Biomass composition can be modified to create varieties that are efficiently broken down to release cell wall sugars. This study focused on identifying the key biomass components influencing plant cell wall recalcitrance that can be targeted for selection in sugarcane, an important and abundant source of biomass. RESULTS: Biomass composition and the amount of glucan converted into glucose after saccharification were measured in leaf and culm tissues from seven sugarcane genotypes varying in fiber composition after no pretreatment and dilute acid, hydrothermal and ionic liquid pretreatments. In extractives-free sugarcane leaf and culm tissue, glucan, xylan, acid-insoluble lignin (AIL) and acid-soluble lignin (ASL) ranged from 20 to 32%, 15% to 21%, 14% to 20% and 2% to 4%, respectively. The ratio of syringyl (S) to guaiacyl (G) content in the lignin ranged from 1.5 to 2.2 in the culm and from 0.65 to 1.1 in the leaf. Hydrothermal and dilute acid pretreatments predominantly reduced xylan content, while the ionic liquid (IL) pretreatment targeted AIL reduction. The amount of glucan converted into glucose after 26 h of pre-saccharification was highest after IL pretreatment (42% in culm and 63.5% in leaf) compared to the other pretreatments. Additionally, glucan conversion in leaf tissues was approximately 1.5-fold of that in culm tissues. Percent glucan conversion varied between genotypes but there was no genotype that was superior to all others across the pretreatment groups. Path analysis revealed that S/G ratio, AIL and xylan had the strongest negative associations with percent glucan conversion, while ASL and glucan content had strong positive influences. CONCLUSION: To improve saccharification efficiency of lignocellulosic biomass, breeders should focus on reducing S/G ratio, xylan and AIL content and increasing ASL and glucan content. This will be key for the development of sugarcane varieties for bioenergy uses.

Use of licap and ltap flaps for breast reconstruction.

Breast conserving surgery has been reserved for patients with favorable proportion between tumor dimensions and breast size. Introduction of local flaps from the lateral thoracic region has widened the indications for breast conserving surgery, by allowing surgeons to perform wider excisions, thus yet be able to ensure tumor-free surgical margins and a good aesthetic result. We have used lateral intercostal perforator flaps and flaps harvested on the lateral thoracic artery and lateral thoracic artery axial flap in patients with small breasts and an unfavorable tumor to breast size proportion. From May 2015 to October 2016, 19 patients with breast tumors have been treated with BCS and immediate volume replacement reconstruction by pedicle perforator flaps from the lateral thoracic region. In 15 patients lateral intercostal artery perforator flaps or lateral thoracic artery perforator flaps were used after quadrantectomy or wide local excision, in 3 patients as volume replacement after mastectomy and in 1 patient after mastectomy following previous augmentation mammoplasty. In all patients, good breast symmetry was achieved, with no major complications. Fibrosis of the flap and residual breast parenchyma, with volume reduction were noticed after postoperative radiotherapy in thin patients or flaps with little subcutaneous fat. Perforator flaps from the lateral thoracic region should become the gold standard for reconstructions after breast conserving surgery involving less than 20% of the breast volume or after mastectomy in patients with small breasts. The operating procedure is safe, quick and allows sparing of the latissimus dorsi muscle and thus minimal donor site morbidity, as well as an excellent aesthetic result.

Allergy in adolescent population (14-18 years) living in Campania region (Southern Italy). A multicenter study.

Summary: Adolescents (Ad) constitute a difficult to manage population among individuals suffering from asthma. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic Ad living in the Campania region (Southern Italy). Sixteen Allergy units or Centers belonging to the Italian Association of Hospital and Territorial Allergologists (AAIITO, Campania region) participated in this cross-sectional study. A case report form (CRF) was specifically designed for this study and commercial allergen extracts used for screening SPTs were provided by ALK-Abelló Group (Milan, Italy). A total of 443 patients were examined (females, f 220, 49.6 %; males, m 223, 50.3%). Dust mites represent the most common sensitizing agents in allergic Ad living in Campania region (Dermatoph. pteronyssinus 67.4% and Dermatoph. farinae 66.5%), followed by Parietaria (58.9%), grasses (45.8%), Artemisia vulgaris (16.7%), Olea Europaea (32.2%), dog dander (17.1%), cat dander (20.0%), Alternaria alternata (8.1%), Cupressus sempervirens (4.9%), Betula pendula (4.7%), other allergens (19.4%). An interesting comparison has been made between clinical data of our Ad with data of elderly patients (E). The role of allergic sensitization is significantly higher in Ad compared to E. Dermatophagoides pteronyssinus is the first sensitizing allergen in Ad and the last in E. Parietaria constitutes the first sensitizing pollen both in Ad and E, the percentage of sensitization is higher in Ad. Another important difference is the higher prevalence of As, as only symptom, in E compared to Ad (19.7% versus 7.6%). In conclusion, our findings confirm the high prevalence and clinical significance of airway allergic sensitization in the adolescents living in Campania region.

PATIENT SATISFACTION AFTER BREAST RECONSTRUCTION: IMPLANTS VS. AUTOLOGOUS TISSUES.

INTRODUCTION: Breast reconstruction is increasingly present in the treatment of breast cancer. It may be accomplished with implants or autologous tissues. This cross-sectional study evaluates patients satisfaction and quality of life in women after successful autologous or implant breast reconstruction. MATERIAL AND METHODS: 109 women who successfully underwent breast reconstruction between 2007 and 2016 were included. The patients completed the BREAST-Q questionnaire at follow-up visits. Additional data were collected retrospectively from the hospital charts regarding complications, smoking, chemotherapy, radiotherapy, unilateral or bilateral reconstruction, BMI and comorbidities. Mann-Whitney U Test was applied to evaluate differences between the autologous breast reconstruction group (n = 50) and the implant breast reconstruction group (n = 59). RESULTS: Women with a successful autologous reconstruction were significantly more satisfied with their reconstructed breasts than women with successful alloplastic breast reconstruction as measured by the BREAST-Q breasts module (p = 0. 00596), psycho-social well-being module (p=0.04) and sexual well-being module (p=0.00068). Furthermore, there is a higher degree of satisfaction in patients who have not undergone radiotherapy, with no complications and with a normal BMI for implant reconstruction group as well as in non-smokers, and bilateral reconstructions for flap reconstruction group. DISCUSSION: The findings of our study are in agreement with the data found in the literature, attributing greater satisfaction with physical, mental and social wellbeing, as well as with elements having repercussion on sexual wellbeing, to autologous breast reconstruction. CONCLUSIONS: Autologous breast reconstruction leads to higher patient satisfaction than implant breast reconstruction. This study may help patients and medical teams in their decision-making process regarding breast reconstruction. This pilot study opens several questions that need further investigations in a larger prospective studyKeywords: Breast reconstruction, breast-Q, satisfaction, implant, autologous tissue.

Abnormal brain oscillations persist after recovery from bipolar depression.

When directly perturbed in healthy subjects, premotor cortical areas generate electrical oscillations in the beta range (20-40Hz). In schizophrenia, major depressive disorder and bipolar disorder (BD), these oscillations are markedly reduced, in terms of amplitude and frequency. However, it still remains unclear whether these abnormalities can be modulated over time, or if they can be still observed after treatment. Here, we employed transcranial magnetic stimulation (TMS) combined with EEG to assess the frontal oscillatory activity in eighteen BD patients before/after antidepressant treatments (sleep deprivation and light therapy), relative to nine healthy controls. In order to detect dominant frequencies, event related spectral perturbations (ERSP) were computed for each TMS/EEG session in all participants, using wavelet decomposition. The natural frequency at which the cortical circuit oscillates was calculated as the frequency value with the largest power across 300ms post-stimulus time interval. Severity of depression markedly decreased after treatment with 12 patients achieving response and nine patients achieving remission. TMS/EEG resulted in a significant activation of the beta/gamma band response (21-50Hz) in healthy controls. In patients, the main frequencies of premotor EEG responses to TMS did not significantly change before/after treatment and were always significantly lower than those of controls (11-27Hz) and comparable in patients achieving remission and in those not responding to treatment. These results suggest that the reduction of natural frequencies is a trait marker of BD, independent from the clinical status of the patients. The present findings shed light on the neurobiological underpinning of severe psychiatric disorders and demonstrate that TMS/EEG represents a unique tool to develop biomarkers in psychiatry.

Deeper than skin deep - The effect of botulinum toxin-A on emotion processing.

The effect of facial botulinum Toxin-A (BTX) injections on the processing of emotional stimuli was investigated. The hypothesis, that BTX would interfere with processing of slightly emotional stimuli and less with very emotional or neutral stimuli, was largely confirmed. BTX-users rated slightly emotional sentences and facial expressions, but not very emotional or neutral ones, as less emotional after the treatment. Furthermore, they became slower at categorizing slightly emotional facial expressions under time pressure.

Novelties in COPD prognosis: evolution of survival indexes.

Despite several techniques, such as non-invasive ventilation (NIV), have improved the outcome of the acute exacerbation, COPD remains affected by poor prognosis in the medium and long term. Moreover, the task of predicting prognosis remains a major challenge for respiratory physicians. In order to overcome this limitation, several indexes have been proposed to assess the COPD patient in his/her complexity. The rationale is that, by using numerical indexes physicians may improve their clinical judgment to tailor and share therapeutical choices, i.e. referring the patient for surgery or lung transplantation. On this ground, Almagro et al. recently proposed the CODEX index, as the latest evolution of the BODE through the BODEx (which takes into account exacerbations), by adding the evaluation of comorbidity to the severity of dyspnoea, airway obstruction and history of exacerbations. As afore mentioned, treatment of COPD with respiratory acidosis has been revolutionized by the use of NIV, by reducing the need for intubation and in-hospital mortality of patients with severe COPD exacerbations. Nowadays, new promising techniques, such as minimally invasive extracorporeal devices, may hasten the clearance of carbon dioxide and reduce the work of breathing and the need for ventilation of COPD patients. These techniques still lack of randomized controlled studies; however, the approach of extracorporeal CO2 removal has the potential to further improve the prognosis of severe exacerbation of COPD patients. In this paper we discuss the prognostic evaluation of patients affected by COPD through the evolution of dedicated indexes, which mirror the focus of current research on the disease.

Comparison of different pretreatments for the production of bioethanol and biomethane from corn stover and switchgrass.

In this study the efficiency of mild ionic liquid (IL) pretreatment and pressurized hot water (PHW) is evaluated and compared in terms of bioethanol and biomethane yields, with corn stover (CS) and switchgrass (SG) as model bioenergy crops. Both feedstocks pretreated with the IL 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc] at 100°C for 3h exhibited lower glucose yield that those treated with harsher pretreatment conditions previously used. Compared to PHW, IL pretreatment demonstrated higher bioethanol yields; moreover IL pretreatment enhanced biomethane production. Taking into consideration both bioethanol and biomethane productions, results indicated that when using IL pretreatment, the total energy produced per kg of total solids was higher compared to untreated biomasses. Specifically energy produced from CS and SG was +18.6% and +34.5% respectively, as compared to those obtained by hot water treatment, i.e. +2.3% and +23.4% for CS and SG, respectively.

Abnormal cortico-limbic connectivity during emotional processing correlates with symptom severity in schizophrenia.

BACKGROUND: Impaired emotional processing is a core feature of schizophrenia (SZ). Consistent findings suggested that abnormal emotional processing in SZ could be paralleled by a disrupted functional and structural integrity within the fronto-limbic circuitry. The effective connectivity of emotional circuitry in SZ has never been explored in terms of causal relationship between brain regions. We used functional magnetic resonance imaging and Dynamic Causal Modeling (DCM) to characterize effective connectivity during implicit processing of affective stimuli in SZ. METHODS: We performed DCM to model connectivity between amygdala (Amy), dorsolateral prefrontal cortex (DLPFC), ventral prefrontal cortex (VPFC), fusiform gyrus (FG) and visual cortex (VC) in 25 patients with SZ and 29 HC. Bayesian Model Selection and average were performed to determine the optimal structural model and its parameters. RESULTS: Analyses revealed that patients with SZ are characterized by a significant reduced top-down endogenous connectivity from DLPFC to Amy, an increased connectivity from Amy to VPFC and a decreased driving input to Amy of affective stimuli compared to HC. Furthermore, DLPFC to Amy connection in patients significantly influenced the severity of psychopathology as rated on Positive and Negative Syndrome Scale. CONCLUSIONS: Results suggest a functional disconnection in brain network that contributes to the symptomatic outcome of the disorder. Our findings support the study of effective connectivity within cortico-limbic structures as a marker of severity and treatment efficacy in SZ.

Fronto-limbic disconnection in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a severe, disabling and life-threatening illness. Disturbances in emotion and affective processing are core features of the disorder with affective instability being paralleled by mood-congruent biases in information processing that influence evaluative processes and social judgment. Several lines of evidence, coming from neuropsychological and imaging studies, suggest that disrupted neural connectivity could play a role in the mechanistic explanation of these cognitive and emotional symptoms. The aim of the present study is to investigate the effective connectivity in a sample of bipolar patients. METHODS: Dynamic causal modeling (DCM) technique was used to study 52 inpatients affected by bipolar disorders consecutively admitted to San Raffaele hospital in Milano and forty healthy subjects. A face-matching task was used as activation paradigm. RESULTS: Patients with BD showed a significantly reduced endogenous connectivity in the DLPFC to Amy connection. There was no significant group effect upon the endogenous connection from Amy to ACC, from ACC to Amy and from DLPFC to ACC. CONCLUSIONS: Both DLPFC and ACC are part of a network implicated in emotion regulation and share strong reciprocal connections with the amygdale. The pattern of abnormal or reduced connectivity between DLPFC and amygdala may reflect abnormal modulation of mood and emotion typical of bipolar patients.

Compared to coverage by STSG grafts only reconstruction by the dermal substitute Integra® plus STSG increases TcPO2 values in diabetic feet at 3 and 6 months after reconstruction*.

AIM: Purpose of this retrospective comparative study is to evaluate the results of reconstruction of diabetic feet by split thickness skin graft (STSG) and by dermal substitute Integra® covered by STSG in terms of vascularity of the reconstructed wound-bed by measurements of tissue oxygenation (TcPO2). PATIENTS AND METHODS: 23 patients were included into the study (12 were reconstructed by STSG only and 11 with Integra® and STSG three weeks later). In each patient TcPO2 measurements were performed at the same spot of the reconstructed area at 14 days, one month, 3 months, 6 months, 12 months and 24 months after reconstruction. RESULTS: Wound beds reconstructed by Integra® showed on average 10 mmHg higher TcPO2. CONCLUSIONS: Our study estimated in an objective way, by TcPO2 value measurements, the oxygenation of the wound bed in diabetic feet after reconstruction by STSG only and after adding dermal substitute Integra® to the wound bed before final STSG coverage. During first month after reconstruction no statistically significant differences were found. After 3 months TcPO2 studies revealed statistically significant higher oxygen tissue pressure in diabetic feet covered by Integra® plus STSG. These findings endorse in an objective way the clinical findings already reported while using the dermal substitute. It remains to explain the role of this increase of oxygen tissue pressure in redefine the indications for the use of dermal substitutes in reconstruction of poor vascularized regions.

Are benzodiazepines and opioids really safe in patients with severe COPD?

Breathlessness is a key symptom in chronic obstructive pulmonary disease (COPD) with prognostic implications on health status and survival. Since most conditions underlying chronic refractory breathlessness in COPD are not modifiable, the use of opioids and benzodiazepines has been proposed to relieve it. However, respiratory depression is a known adverse event of these drugs, and concerns have been raised on their use in patients with chronic respiratory failure. Despite safety-related concerns, benzodiazepines are frequently prescribed for a variety of reasons, including treatment of insomnia, depression and anxiety, as well as to relieve refractory dyspnea in patients with COPD. The key role of opioids in the end-of-life and in the management of dyspnea that is unresponsive to best-possible disease management is recognized. Moreover, the use of low dose opioids to treat dyspnea, discomfort or refusal for patient undergoing non-invasive ventilation is still debated. In the current review, we aim at discussing and analyzing recently published findings on the use of benzodiazepines and opioids in patients with COPD and at reviewing the literature on this topic. Recent observations favor the use of lower doses of opioids (≤30 mg oral morphine equivalents/day) for reduction of symptoms in those patients with severe COPD receiving long-term oxygen therapy. Low dose opioids are not associated with an increased risk of hospital admission or death in cohorts of COPD patients on long term oxygen therapy. On the contrary, benzodiazepines and opioids at higher doses might increase mortality.

Potentially harmful effects of inspiratory synchronization during pressure preset ventilation.

PURPOSE: Pressure preset ventilation (PPV) modes with set inspiratory time can be classified according to their ability to synchronize pressure delivery with patient's inspiratory efforts (i-synchronization). Non-i-synchronized (like airway pressure release ventilation, APRV), partially i-synchronized (like biphasic airway pressure), and fully i-synchronized modes (like assist-pressure control) can be distinguished. Under identical ventilatory settings across PPV modes, the degree of i-synchronization may affect tidal volume (VT), transpulmonary pressure (PTP), and their variability. We performed bench and clinical studies. METHODS: In the bench study, all the PPV modes of five ventilators were tested with an active lung simulator. Spontaneous efforts of -10 cmH2O at rates of 20 and 30 breaths/min were simulated. Ventilator settings were high pressure 30 cmH2O, positive end-expiratory pressure (PEEP) 15 cmH2O, frequency 15 breaths/min, and inspiratory to expiratory ratios (I:E) 1:3 and 3:1. In the clinical studies, data from eight intubated patients suffering from acute respiratory distress syndrome (ARDS) and ventilated with APRV were compared to the bench tests. In four additional ARDS patients, each of the PPV modes was compared. RESULTS: As the degree of i-synchronization among the different PPV modes increased, mean VT and PTP swings markedly increased while breathing variability decreased. This was consistent with clinical comparison in four ARDS patients. Observational results in eight ARDS patients show low VT and a high variability with APRV. CONCLUSION: Despite identical ventilator settings, the different PPV modes lead to substantial differences in VT, PTP, and breathing variability in the presence spontaneous efforts. Clinicians should be aware of the possible harmful effects of i-synchronization especially when high VT is undesirable.

Effect of vascular endothelial growth factor gene therapy on post-traumatic peripheral nerve regeneration and denervation-related muscle atrophy.

Functional recovery after peripheral nerve injury depends on both improvement of nerve regeneration and prevention of denervation-related skeletal muscle atrophy. To reach these goals, in this study we overexpressed vascular endothelial growth factor (VEGF) by means of local gene transfer with adeno-associated virus (AAV). Local gene transfer in the regenerating peripheral nerve was obtained by reconstructing a 1-cm-long rat median nerve defect using a vein segment filled with skeletal muscle fibers that have been previously injected with either AAV2-VEGF or AAV2-LacZ, and the morphofunctional outcome of nerve regeneration was assessed 3 months after surgery. Surprisingly, results showed that overexpression of VEGF in the muscle-vein-combined guide led to a worse nerve regeneration in comparison with AAV-LacZ controls. Local gene transfer in the denervated muscle was obtained by direct injection of either AAV2-VEGF or AAV2-LacZ in the flexor digitorum sublimis muscle after median nerve transection and results showed a significantly lower progression of muscle atrophy in AAV2-VEGF-treated muscles in comparison with muscles treated with AAV2-LacZ. Altogether, our results suggest that local delivery of VEGF by AAV2-VEGF-injected transplanted muscle fibers do not represent a rational approach to promote axonal regeneration along a venous nerve guide. By contrast, AAV2-VEGF direct local injection in denervated skeletal muscle significantly attenuates denervation-related atrophy, thus representing a promising strategy for improving the outcome of post-traumatic neuromuscular recovery after nerve injury and repair.

Recent advances in interfaces for non-invasive ventilation: from bench studies to practical issues.

The interface is the defining element of non-invasive ventilation (NIV). Nowadays different types of interfaces, which differ in terms of shape, mechanical properties and comfort, are available, and their choice and fitting is a key element of NIV success. In the last decade, larger masks covering the entire face and specifically designed helmets have been developed for delivering NIV, theoretically improving comfort and patient tolerance. Recent studies have shown that, despite marked heterogeneity in mask internal volume and compliance, the dynamic dead space and, above all, the clinical efficacy of different masks is on average very similar. Thus, with the exception of the nasal mask and the mouthpiece, a variety of interfaces for NIV can be used in the acute care setting. However, prevention and monitoring of interfaces related side-effects and evaluation of patient tolerance are crucial to avoid NIV failure. To optimize effectiveness and costs, an interface strategy for NIV in acute respiratory failure could be convenient in clinical practice.

Exploring the effect of different plant lignin content and composition on ionic liquid pretreatment efficiency and enzymatic saccharification of Eucalyptus globulus L. mutants.

There are several approaches being investigated to improve the efficiency of biomass conversion into fermentable sugars, including those that engineer the feedstocks to enhance digestibility. In this study it was evaluated the impact of genotype modifications of three mutants of Eucalyptus globulus L., and of the corresponding wild type on cellulose hydrolyzability before and after ionic liquid (IL) pretreatment. Both untreated and IL-treated samples were chemically characterized and tested for cellulose hydrolizability. Results obtained indicate that genetic modifications altered wood lignin-S/G ratio. This alteration resulted in a different hydrolyzability of cellulose for untreated samples, i.e. high lignin-S/G ratio produced low glucose yield (r=-0.97; P<0.03; n=4), but did not affect glucose yield after IL pretreatment. IL pretreated samples had increased glucose yields compared to that of untreated samples due to the modification of microcrystalline cellulose I to mixtures of more hydrolysable cellulose II and amorphous cellulose, and to the partial removal of the steric impediment, or removal of the lignin "sheath" protecting cellulose, to enzymes. The efficiency of the IL pretreatment used in this study does not appear to be affected by the S/G content of the E. globulus.