On-line tracking of the human gut microbial metabolism: high-throughput screening during colonic in-vitro fermentation

The human gut encloses a large community of bacteria producing a wide range of volatile organic compounds (VOCs) when fermenting undigestible substrates. This study aims to provide a high throughput method to study in real-time the gut microbial volatilome when the microbiota process undigestible dietary substrates. Background: Small metabolites from the human gut microbiota are recognized as the intermediates of the microbiome-host cross-talk [1]. The research on the human gut metabolome is mainly based on discrete sampling representing discontinuous ‘snapshot’ of these complex biological systems [2]. The aim of this research work is to enhance the current understanding of the dynamics of the gut microbiota by integrating non-invasive and continuous analytical methods with in-vitro gut simulators, to monitor in real-time, the progression of small molecules released into the headspace [2,3] Methodology: Automated Head space-Solid Phase Micro Extraction coupled with Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) and Static Headspace- Proton Transfer Reaction-Time of Flight-Mass Spectrometry (SHS-PTR-ToF-MS) are used for the purpose of this investigation. The objective is to screen and monitor a specific set of masses of interest, to gain system level mechanistic insights on primary metabolism of the gut microbial consortia. Results: This methodology enabled the continuous monitoring of multiple metabolites in time, including short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) derived from 24h oat bran fermentation. A mixture of -odd and -even chain acids were co-released into the culture headspace after 4 hours of fermentation and their relative abundance increased in time over 24 hours. The production of multiple MCFAs from the substrate is most likely a community optimization strategy to maximize ATP production from oat degradation by means of reverse beta-oxidation which involves the utilization of fermentation intermediates, such as propanol and acetate. Furthermore, the untargeted screening allowed the detection of low abundant sulfur metabolites, thiophenes, which, to our knowledge, were never investigated before as gut microbial metabolites (GMMs). Conclusion: By integrating non-invasive and continuous analytical methods with an in-vitro gut simulator, it was possible to monitor in real-time the progression of two important class of small molecules released by the microbial consortia into the headspace. The collected information can be jointly integrated to shed light on the dynamics of bacterial foraging of complex undigestible substrates (e.g. bran from cereals). Overall, these results confirm the idea to consider the bacterial headspace as a highly dynamic chemical system that contains information on microbial community behavio

Recent advances in miniaturized optical gyroscopes

Low-cost chip-scale optoelectronic gyroscopes having a resolution ≤ 10 °/h and a good reliability also in harsh environments could have a strong impact on the medium/high performance gyro market, which is currently dominated by well-established bulk optical angular velocity sensors. The R&D activity aiming at the demonstration of those miniaturized sensors is crucial for aerospace/defense industry, and thus it is attracting an increasing research effort and notably funds.  In this paper the recent technological advances on the compact optoelectronic gyroscopes with low weight and high energy saving are reviewed. Attention is paid to both the so-called gyroscope-on-a-chip, which is a novel sensor, at the infantile stage, whose optical components are monolithically integrated on a single indium phosphide chip, and to a new ultra-high Q ring resonator for gyro applications with a configuration including a 1D photonic crystal in the resonant path. The emerging field of the gyros based on passive ring cavities, which have already shown performance comparable with that of optical fiber gyros, is also discussed

Cranio-Mandibular Disorders after Whiplash Injury: A Mono-Institutional Clinical Study on 31 Patients

Background: Whiplash is a consequence of traumatic injuries, mostly related to road accidents, with variable clinical manifestations, also known as Whiplash Associated Disorders, such as neck, head and temporo-cranio-mandibular pain. Methods: The current study aims to evaluate the onset and evolution of temporomandibular joint pain in people with whiplash in a study group treated with the use of Zimmer Collars (adjustable rigid cervical collars for neck immobilization), as compared to a control group. This prospective study included 31 patients followed by the Dental Prosthesis Department of the University of Bari “Aldo Moro”: 20 patients with whiplash (age range: 20–39 years) treated with Zimmer collars and 11 patients with whiplash (age range: 20–33 years) who were not. Immediately after the whiplash occurred, a visual analogue scale (VAS) was used to describe the intensity of pain and to complete the chart of the European Academy of Craniomandibular Disorders. Five out of twenty patients, already treated with a Zimmer collar, wore an occlusal splint as well because of persistent pain reported at the 28-day and 60-day follow-up and were supported by pharmacological therapy with analgesics (paracetamol) and muscle relaxants (thiocolchicoside). Results: During the last follow-up (at six months), three out of five patients displayed a residual VAS score of 3, 4, and 5, respectively, while the remaining two displayed a VAS of 0. In the control group, four out of eleven patients needed to wear an occlusal splint but without muscle relaxants and analgesics pharmacological therapy; these four corresponded to the patients showing a residual painful symptomatology, with VAS reaching value of 2, and also were the oldest patients of the group. Data regarding VAS values and Zimmer collar use, both at the first visit and six months later, were statistically analyzed. Conclusion: Our prospective study highlights how whiplash-associated acute disorders are often self-limiting over a period of few months, thus reducing the possibility of symptom chronicity; the latter seems to be strictly related to lesion severity, pre-existence of a craniomandibular dysfunction and patient age, but appears to be independent from Zimmer collar use, as statistically confirmed

Vinblastine, bleomycin, and methotrexate chemotherapy plus irradiation for patients with early-stage, favorable Hodgkin lymphoma - The experience of the gruppo italiano studio linfomi

BACKGROUND. The acknowledged effectiveness of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy in patients with early-stage Hodgkin lymphoma has been associated with conflicting toxicity reports. METHODS. One hundred forty-three patients were evaluated clinically and had favorable Stage IA or IIA Hodgkin lymphoma. Ninety-three patients were treated with the standard VBM schedule combined with extended-field radiotherapy (EFRT), leaving the choice of the therapeutic sequence free. Fifty subsequent patients were treated with a slightly modified VBM schedule (VbMp) combined with RT limited to involved fields (IF-RT) and delivered only after the end of chemotherapy. In the VbMp schedule, intervals between cycles were 21 days instead of 28 days, bleomycin doses were reduced, small doses of prednisone were given orally, and the interval before RT was prolonged. RESULTS. Clinical response was complete in 96% of patients who were treated with VBM plus EF-RT and in 94% of patients who were treated with VbMp plus IF-RT. Recurrence rates were nearly identical (12% and 11%, respectively) over necessarily different follow-up (91 months and 33 months, respectively). Hematologic toxicity was tolerable in both trials, and pulmonary side effects were moderate in the first trial and negligible in the second. On the whole, treatment was tolerated better when RT followed chemotherapy. CONCLUSIONS. The VBM regimen was confirmed to be effective in patients with early-stage Hodgkin lymphoma. Administration of all cycles before RT improved tolerance; pulmonary toxicity probably is mitigated further by reduced bleomycin doses, mild prednisone therapy, and a more prolonged resting interval before RT. A slightly higher recurrence rate was expectable in the VBM plus IF-RT trial despite the actual intensification of vinblastine and methotrexate

Primary diffuse large B-cell lymphoma of the breast: prognostic factors and outcomes of a study by the International Extranodal Lymphoma Study Group

Background: Primary diffuse large B-cell lymphoma (DLBCL) of breast is rare. We aimed to define clinical features, prognostic factors, patterns of failure, and treatment outcomes. Patients and methods: A retrospective international study of 204 eligible patients presenting to the International Extranodal Lymphoma Study Group-affiliated institutions from 1980 to 2003. Results: Median age was 64 years, with 95% of patients presenting with unilateral disease. Median overall survival (OS) was 8.0 years, and median progression-free survival 5.5 years. In multifactor analysis, favourable International Prognostic Index score, anthracycline-containing chemotherapy, and radiotherapy (RT) were significantly associated with longer OS (each P ≤ 0.03). There was no benefit from mastectomy, as opposed to biopsy or lumpectomy only. At a median follow-up time of 5.5 years, 37% of patients had progressed—16% in the same or contralateral breast, 5% in the central nervous system, and 14% in other extranodal sites. Conclusions: The combination of limited surgery, anthracycline-containing chemotherapy, and involved-field RT produced the best outcome in the pre-rituximab era. A prospective trial on the basis of these results should be pursued to confirm these observations and to determine whether the impact of rituximab on the patterns of relapse and outcome parallels that of DLBCL presenting at other site