Intensification of the freeze drying process by the control of both freezing and primary drying steps

The problem of optimization of freeze-drying cycles is addressed, with emphasis in both freezing and primary drying steps. In particular, this study shows that the control of the nucleation event produces more uniform batches (as ice nucleation is induced in all the vials of batch almost at the same time and temperature) and allows a marked reduction in the duration of the optimized cycle (if compared to cycles carried out with conventional stochastic nucleation)

Effect of vacuum induced nucleation on the final product homogeneity

In the field of freeze drying of pharmaceutics the homogeneity of the sublimation flux during drying is fundamental to allow a final product with the same characteristics. Previous studies have shown that the control of freezing stage, in addition to a dramatic reduction of cycle duration, can also improve the homogeneity of the final batch. In this framework, this study is focused on the investigation of the effects of the Vacuum Induced Nucleation control method (modified in a previous work)[1,2] on the final structure of the product. Two aspects will be taken into consideration: the uniformity among vials of the same batch (inter-vial) and the uniformity of the structure along the height of the product (intra-vial). It has to be pointed out that a non-uniform product structure can have an impact on the protein aggregation and redistribution, and cause a partial cake collapse or micro-collapse. This investigation is really useful to define some limits of the control method used in this work

Vacuum-Induced Surface Freezing for the Freeze-Drying of the Human Growth Hormone: How Does Nucleation Control Affect Protein Stability?

Abstract In the present work, the effect of controlled nucleation on the stability of human growth hormone (hGH) during freeze-drying has been investigated. More specifically, the vacuum-induced surface freezing technique has been compared to conventional freezing, both with and without an annealing step. Size exclusion chromatography and cell-based potency assays have been used to characterize the formation of soluble aggregates and the biological activity of hGH, respectively. The results obtained indicate that controlled nucleation has a positive effect on both cycle performance and product homogeneity because of the formation of bigger ice crystals, and characterized by a narrower dimensional distribution. From the point of view of hGH stability, we observed that vacuum-induced surface freezing is not detrimental to the biological activity of the protein, or aggregate formation. In addition, the effect of 2 different formulations, including trehalose or cellobiose, on protein preservation was also considered for this study

Presence and geodynamic significance of Cambro-Ordovician series of SE Karakaram (N. Pakistan)

New geological, geochemical and geochronological data from the Southern Karakoram (NE Pakistan) indicate the presence of several unexpectedly old and well preserved units along the Asian margin: (1) a Precambrian basement, displaying a minimum amphibole Ar-Ar age of 651 Ma; (2) a thick Cambro-Ordovician platform-type sedimentary unit overlying the Precam-brian basement. These series are dated by graptolite and crinoid faunas, and are confirmed by concordant 87Sr/86Sr and 13C “ages” of the marbles; (3) a dismembered ophiolitic series formed by slices of metagabbros and metabasalts separated by ultramafic lenses (the Masherbrum Greenstone Complex). The occurrence of such Cambro-Ordovician series overlying a Precambrian basement in south-eastern Karakoram similar to the south-western Karakoram shows that the Karakoram constitutes a continuous tectonic block. The petrology and geochemistry of the Masherbrum Greenstone Complex (mineral chemistry, major and trace element and Sr-Nd isotopic data) are indicative of a supra-subductive environment. The presence of LREE-enriched calc-alkaline rocks [(La/Yb)N = 4.45.6; (Nb/La)N = 0.2-0.3; eNd565 = 5.1-7.1] and LREE-depleted tholeiitic rocks [(La/Yb)N =0.5-1.3; (Nb/La)N = 0.6-0.9; eNd565 = 5.6-7.8] are consistent with arc and back-arc settings, respectively. A high-Mg andesitic dolerite and an OIB-type metabasalt, with lower eNd ratios (eNd565 = 0.5 and 4.5) are in accordance with source heterogeneity beneath the arc. The Masherbrum Greenstone Complex, along with other Cambro-Ordovician central-eastern volcanic series give evidence of a tectonic situation governed by micro-plate convergent-divergent systems with occurrence of arc - back-arc settings during the Lower Palaeozoic, comparable to that of the current SW Pacific area

Comparison of preserved bimatoprost 0.01% with preservative-free tafluprost: A randomised, investigator-masked, 3-month crossover, multicentre trial, SPORT II

IMPORTANCE: This study compares the efficacy and tolerability of a preservative-free prostaglandin analogue (tafluprost 15 mg/ml) to a prostaglandin analogue that uses 0.02% of benzalkonium chloride (bimatoprost 0.1 mg/ml). BACKGROUND: Different prostaglandin analogues have been commercially approved, with differences in tolerability. DESIGN: Prospective, randomised, investigator-masked, 3-month crossover, multicentre trial. PARTICIPANTS: Sixty-four patients with ocular hypertension or open-angle glaucoma were randomised to two groups, after a 4-week washout period from their current topical drop regimen. METHODS: Participants were randomised to tafluprost (Group 1; n = 33) or bimatoprost (Group 2; n = 31). At month 3, each group switched to the opposite treatment. IOP was evaluated at multiple timepoints. MAIN OUTCOME MEASURES: The primary outcome was difference in mean IOP between the two groups at the final visit. Secondary outcomes included change from baseline IOP at month 3 and month 6, difference in mean IOP at month 3 and difference in IOP at all timepoints. Safety outcomes included best-corrected visual acuity (BCVA), adverse events, ocular tolerability, optic nerve assessment and slit lamp biomicroscopy. RESULTS: Both medications significantly lowered IOP at month 6 compared to baseline: 5.4 mmHg (27%) for tafluprost and 6.8 mmHg (33%) for bimatoprost (p < 0.0001). No significant differences in any of the safety measures (including conjunctival hypearemia) were detected. CONCLUSIONS AND RELEVANCE: Bimatoprost produced a statistically significant greater IOP reduction compared to tafluprost with minimal to no difference in side effects. This should be borne in mind when weighing up the pros and cons of preserved versus preservative-free prostaglandin analogue therapy

Conventional and algorithmic music listening before radiotherapy treatment: A randomized controlled pilot study

Music listening is a widespread approach in the field of music therapy. In this study, the effects of music listening on anxiety and stress in patients undergoing radiotherapy are investigated. Sixty patients with breast cancer who were candidates for postoperative curative radiotherapy were recruited and randomly assigned to three groups: Melomics-Health (MH) group (music listening algorithmically created, n = 20); individualized music listening (IML) group (playlist of preferred music, n = 20); no music group (n = 20). Music listening was administered for 15 min immediately before simulation and during the first five radiotherapy sessions. The State-Trait Anxiety Inventory (STAI) and the Psychological Distress Inventory (PDI) were administered before/after treatment. Cochran’s Q test and McNemar test for paired proportions were performed to evaluate if the proportion of subjects having an outcome score below the critical value by treatment and over time was different, and if there was a change in that proportion. The MH group improved in STAI and PDI. The IML group worsened in STAI at T1 and improved STAI-Trait at T2. The IML group worsened in PDI at T2. The No music group generally improved in STAI and PDI. Clinical and music listening-related implications are discussed defining possible research perspectives in this field

The Reliability of Anamnestic Data in the Management of Clostridium Tetani Infection in Elderly

Background: Tetanus infection remains a significant complication of wounds. Because most tetanus treatment guidelines rely on anamnestic data collected directly from patients, the congruence between anamnesis and laboratory evidence must be verified, especially in the elderly population. Aim: Assess, in both the geriatric population (&gt;65) and the non-geriatric one, the reliability of anamnestic data for managing patients with tetanus-risk wounds, identified categories of populations most exposed to non-vaccination coverage, and assessed the agreement of the Tetanos Quick Stick (TQS) results with the therapy performed (administration of tetanus vaccine or immunoglobulin). Methods: In this retrospective single-center observational study, patients were asked their immunization status against tetanus vaccination. The decision to administer a vaccine or immunoglobulin was therefore clinical and based on anamnestic criteria. The TQS test was then given to patients who were unaware of their immunity status. Patients who thought they knew it but were not sure were given the TQS test to determine whether the anamnestic collection was supported by the test. The TQS test results were compared with the anamnestic data. Results: Most patients, geriatric and not geriatric, did not know their immune status. Among those who reported knowing their immune status, there was no agreement between the vaccine coverage declared by patients and the TQS test results (p &lt; 0.001), mainly in geriatric patients but also in the control group. Elderly and women had significantly lower positive TQS test results (p &lt; 0.001). There was a statistically significant discrepancy (p &lt; 0.001) between the therapy based on anamnestic data and the TQS test results. Conclusion: The reliability of anamnestic data for the management of patients with tetanus-risk wounds is low and decreases with age, becoming minimal in geriatric patients. Elderly and women are less likely to have an effective vaccination status against tetanus

267 Occupation and Multiple Sclerosis: an Italian case-control study

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