Miracle-dz/UniFAR-FTUs huggingface dataset:
Persistent adrenocorticotropin response to desmopressin in the early postoperative period predicts recurrence of Cushing's disease.

CONTEXT Patients with Cushing's disease (CD) often show an ACTH and cortisol response to desmopressin (DDAVP). OBJECTIVE We tested whether persistence of a positive response to DDAVP after successful surgery identifies patients at risk of CD recurrence. DESIGN We prospectively included all CD patients who had a positive response to DDAVP before successful surgery from 1995 through 2007. SETTING The study was performed at a university hospital. PATIENTS One hundred seventy-four patients with CD, 148 women and 26 men, mean age 36.1 +/- 0.8 yr, were studied. The median follow-up after surgery was 58 months (interquartile range 22-93 months). INTERVENTION DDAVP test was performed immediately before and after surgery. MAIN OUTCOME MEASURE An ACTH and cortisol increment of at least 30 and 20% above baseline, respectively, were considered as a positive response to DDAVP. The risk of CD recurrence was analyzed according to the postoperative hormonal response to DDAVP. RESULTS Recurrence of CD occurred in 19 patients (10.9%). The recurrence-free survival at 5 yr was 89.8% [95% confidence interval (CI) 84.2-95.4]. Patients with a positive ACTH response had a 5-yr recurrence-free survival of 82.6% (95% CI 70.6-94.6%) as compared with 94.0% (95% CI 88.2-99.8%; P < 0.01) in patients without it. Multivariate analysis showed that persistence of a positive ACTH response to DDAVP was significantly associated with CD recurrence. CONCLUSION Positive ACTH response to DDAVP after surgery is associated with an increased risk of CD recurrence. However, the specificity and predictive value of this finding are low.
Effects of cognitive therapy versus interpersonal psychotherapy in patients with major depressive disorder: a systematic review of randomized clinical trials with meta-analyses and trial sequential analyses

Background Major depressive disorder afflicts an estimated 17% of individuals during their lifetime at tremendous suffering and cost. Cognitive therapy and interpersonal psychotherapy are treatment options, but their effects have only been limitedly compared in systematic reviews. Method Using Cochrane systematic review methodology we compared the benefits and harm of cognitive therapy versus interpersonal psychotherapy for major depressive disorder. Trials were identified by searching the Cochrane Library's CENTRAL, Medline via PubMed, EMBASE, Psychlit, PsycInfo, and Science Citation Index Expanded until February 2010. Continuous outcome measures were assessed by mean difference and dichotomous outcomes by odds ratio. We conducted trial sequential analysis to control for random errors. Results We included seven trials randomizing 741 participants. All trials had high risk of bias. Meta-analysis of the four trials reporting data at cessation of treatment on the Hamilton Rating Scale for Depression showed no significant difference between the two interventions [mean difference −1.02, 95% confidence interval (CI) −2.35 to 0.32]. Meta-analysis of the five trials reporting data at cessation of treatment on the Beck Depression Inventory showed comparable results (mean difference −1.29, 95% CI −2.73 to 0.14). Trial sequential analysis indicated that more data are needed to definitively settle the question of a differential effect. None of the included trial reported on adverse events. Conclusions Randomized trials with low risk of bias and low risk of random errors are needed, although the effects of cognitive therapy and interpersonal psychotherapy do not seem to differ significantly regarding depressive symptoms. Future trials should report on adverse events.
Perception of the esthetic impact of mandibular incisor extraction treatment on laypersons, dental professionals, and dental students.

OBJECTIVE To evaluate the degree of perception of laypersons, dental professionals, and dental students regarding dental esthetics in cases with mandibular central incisor extraction. MATERIALS AND METHODS Using a smile photograph of a person with normal occlusion and all teeth, modifications were made to reflect the extraction of a mandibular incisor of various compositions and sizes. For this purpose a program specifically for image manipulation (Adobe Photoshop CS3, Adobe Systems Inc) was used. After manipulation the images were printed on photographic paper, attached to a questionnaire and distributed to laypersons, dental professionals, and dental students (n = 90) to evaluate the degree of perception and esthetic using a scale of attractiveness, where 0 = hardly attractive, 5 = attractive, and 10 = very attractive. The differences between examiners were checked by the Mann-Whitney test. All the statistics were performed with a confidence level of 95%. RESULTS The results demonstrated the skill of the dental professionals and dental students in perceiving the difference between cases of normal occlusion and cases where an incisor was lacking (P < .05). The photograph in which the lateral incisors were shown to be larger than the central incisor was the one that obtained the highest value among the cases of extraction in all groups of evaluators. CONCLUSIONS It can be concluded that dental professionals and dental students are more skillful at identifying deviation from normality. In addition, central incisor extraction should always be discarded when there are other treatment options available.
The A‐factor regulatory cascade leading to streptomycin biosynthesis in Streptomyces griseus : identification of a target gene of the A‐factor receptor

In Streptomyces griseus, A‐factor (2‐isocapryloyl‐3R‐hydroxymethyl‐γ‐butyrolactone) at an extremely low concentration triggers streptomycin biosynthesis and cell differentiation by binding a repressor‐type receptor protein (ArpA) and dissociating it from DNA. An A‐factor‐responsive transcriptional activator (AdpA) able to bind the promoter of strR, a pathway‐specific regulatory gene responsible for transcription of other streptomycin biosynthetic genes, was purified to homogeneity and adpA was cloned by PCR on the basis of amino acid sequences of purified AdpA. adpA encoding a 405‐amino‐acid protein containing a helix‐turn‐helix DNA‐binding motif at the central region showed sequence similarity to transcriptional regulators in the AraC/XylS family. The −35 and −10 regions of the adpA promoter were found to be a target of ArpA; ArpA bound the promoter region in the absence of A‐factor and exogenous addition of A‐factor to the DNA–ArpA complex immediately released ArpA from the DNA. Consistent with this, S1 nuclease mapping showed that adpA was transcribed only in the presence of A‐factor and strR was transcribed only in the presence of intact adpA. Furthermore, adpA disruptants produced no streptomycin and overexpression of adpA caused the wild‐type S. griseus strain to produce streptomycin at an earlier growth stage in a larger amount. On the basis of these findings, we propose here a model to demonstrate how A‐factor triggers streptomycin biosynthesis at a late exponential growth stage.
Effectiveness of an SMS-based maternal mHealth intervention to improve clinical outcomes of HIV-positive pregnant women

ABSTRACT We conducted a retrospective study to investigate the effectiveness of an mHealth messaging intervention aiming to improve maternal health and HIV outcomes. Maternal health SMSs were sent to 235 HIV-infected pregnant women twice per week in pregnancy and continued until the infant’s first birthday. The messages were timed to the stage of the pregnancy/infant age and covered maternal health and HIV-support information. Outcomes, measured as antenatal care (ANC) visits, birth outcomes and infant HIV testing, were compared to a control group of 586 HIV-infected pregnant women who received no SMS intervention. Results showed that intervention participants attended more ANC visits (5.16 vs. 3.95, p < 0.01) and were more likely to attend at least the recommended four ANC visits (relative risk (RR): 1.41, 95% confidence interval (CI): 1.15–1.72). Birth outcomes of intervention participants improved as they had an increased chance of a normal vaginal delivery (RR: 1.10, 95% CI: 1.02–1.19) and a lower risk of delivering a low-birth weight infant (<2500 g) (RR: 0.14, 95% CI: 0.02–1.07). In the intervention group, there was a trend towards higher attendance to infant polymerase chain reaction (PCR) testing within six weeks after birth (81.3% vs. 75.4%, p = 0.06) and a lower mean infant age in weeks at HIV PCR testing (9.5 weeks vs. 11.1 weeks, p = 0.14). These results add to the growing evidence that mHealth interventions can have a positive impact on health outcomes and should be scaled nationally following comprehensive evaluation.
Recipient Vessel Analysis for Microvascular Reconstruction of the Head and Neck

The selection of recipient vessels that are suitable for microvascular anastomosis in the head and neck region is one of many components that is essential for successful free tissue transfer. The purpose of this study was to evaluate a set of factors that are related to the recipient artery and vein and to determine how these factors influence flap survival. A retrospective review of 102 patients over a 5-year consecutive period was completed. Indications for microvascular reconstruction included tumor ablation (n = 76), trauma (n = 13), and chronic wounds or facial paralysis (n = 13). The most frequently used recipient artery and vein included the facial, superficial temporal, superior thyroid, carotid, and jugular. Various factors that were related to the recipient vessels were analyzed and included patient age, recipient artery and vein, diabetes mellitus, tobacco use, the timing of reconstruction, the method of anastomosis, previous radiation therapy, creation of an arteriovenous loop, and use of an interposition vein graft. Successful free tissue transfer was obtained in 97 of 102 flaps (95%). Flap failure was the result of venous thrombosis in 4 and arterial thrombosis in 1. Statistical analysis demonstrated that anastomotic failure was associated with an arteriovenous loop (2 of 5, P = 0.03) and tobacco use (3 of 5, P = 0.03). Flap failure was not related to patient age, choice of recipient vessel, diabetes mellitus, previous irradiation, the method of arterial or venous anastomosis, use of an interposition vein graft, or the timing of reconstruction.
Instilled or Injected Purified Natural Capsaicin Has No Adverse Effects on Rat Hindlimb Sensory-Motor Behavior or Osteotomy Repair

BACKGROUND: A novel formulation of ≥98% pure capsaicin (4975) is currently undergoing clinical investigation using novel routes of delivery to provide selective analgesia lasting weeks to months with a single dose. We conducted this study to assess the safety and effects of instilled and injected 4975 in rat models of wound healing osteotomy repair and sensory-motor nerve function. METHODS: Adult male and female Sprague-Dawley rats were used. To assess the effects of 4975 on nerve or muscle, 0.0083 or 0.025 mg 4975 or vehicle (25% polyethylene glycol-300) was applied to exposed sciatic nerve, or 0.1 mg 4975 or vehicle was injected into the surrounding muscle (Group 1). To assess the effect of 4975 on bone healing, an osteotomy was made in one femur and 0.5 mg of 4975 or vehicle was instilled into the site (Group 2). Behavioral testing was performed on both groups of rats and histological evaluation of the sciatic nerve, and surrounding soft tissue and bone was done at days 3, 14, and 28 after surgery. Femurs from osteotomy rats were assessed using peripheral quantitative computed tomography and biomechanical testing. Standard statistical tests were used to compare groups. RESULTS: Rats with direct application of 4975 to the sciatic nerve and surrounding muscle were no different from the controls in nociceptive sensory responses (F = 0.910, P = 0.454), grip strength (F = 0.550, P = 0.654), or histology of the muscle or sciatic nerve. In osteotomy rats, there were no statistical differences between 4975 and vehicle-treated rats for bone area (H = 2.858, P = 0.414), bone mineral content (F = 0.945, P = 0.425), or bone mineral density (F = 0.87, P = 0.462) and no difference in soft tissue healing. There were neither differences in bone stiffness (F = 1.369, P = 0.268) nor were there noticeable differences in the macro- or microscopic appearance of the right femur osteotomy healing site and surrounding soft tissues between the control group and the 4975-treated animals. CONCLUSION: A single, clinically relevant application of instilled or injected 4975 has no observable adverse effect on wound and bone healing after osteotomy or on the structural integrity of exposed muscle and nerve.
Autologous transplantation in multiple myeloma: a GITMO retrospective analysis on 290 patients. Gruppo Italiano Trapianti di Midollo Osseo.

BACKGROUND AND OBJECTIVE Autologous transplantation is a better treatment for multiple myeloma (MM) than chemotherapy, but uncertainty remains about patient selection, optimal timing of autograft, conditioning regimen, need for a second autograft, and role of maintenance. To provide partial answers to these questions we assessed the results of autologous transplantation in a large cohort of patients whose data were reported to the GITMO registry. DESIGN AND METHODS We retrospectively analyzed data from 290 patients with MM (M = 150; F = 140; median age 52 years, range 19-70; stage I = 34, stage II = 75, stage III = 167) reported to the GITMO. At the time of autograft, 20% were in CR, 66% in PR, while the remaining had non-responsive or progressive disease. Median time between diagnosis and transplant was 16 months (1-90). Seventy-two patients (26%) had been planned to receive a double autograft, but this was actually done in only 35 (12%). The conditioning was chemotherapy in 90%. Peripheral blood was the only source of stem cells in 94%, and purging was applied in 10% of cases. For statistical analysis of data, differences between patient subsets were analyzed using the chi-square test, while the Kaplan-Meier method was used to estimate event-free survival (EFS) and survival (OS) probabilities. The Cox model was used for multivariate analysis. RESULTS Following the autograft, 116 patients (40%) were in CR, 144 (50%) in PR, 24 (8%) did not respond or progressed and 6 (2%) died before response evaluation. Transplant-related mortality occurred in 3%. At a median follow-up of 23 months, 223 (77%) patients are alive, 71 (24%) of them in CR, and 67 (23%) patients have died at a median time of 20 months (0-70). OS and EFS at 6 years are 47% and 28%, respectively, but the EFS curve shows no plateau. In multivariate analysis, age, beta2-microglobulin level and status at transplant emerged as significant prognostic factors for both OS and EFS, while time from diagnosis to transplant showed borderline significance. INTERPRETATION AND CONCLUSIONS Based on the prognostic factors identified in multivariate analysis, we were able to assess the weight of a single prognostic factor or their combinations on transplant outcome. We also calculated the probability of OS and EFS by the number of factors at the time of autograft. Autologous transplantation is a safe and effective procedure, not only in sensitive patients, but also in resistant cases, provided they are <55 years of age and have low beta2-microglobulin. It should be applied early after the diagnosis of multiple myeloma, following the delivery of brief primary chemotherapy.
Expression of the different viral mRNAs of human papilloma virus 6 in a squamous‐cell carcinoma of the bladder and the cervix

The prevalence of HPV6 and HPV11 in benign condylomata or mild dysplasias has led to the view of HPV6/11 as rather harmless viruses in relation to carcinogenesis. However, the detection of HPV6/11 DNA in a number of individual cases of squamous‐cell carcinomas of the anogenital/urinary tract could also point to a possible contribution of these viruses in the development of certain malignancies. Recently we have shown that the transcription of the E6 and E7 genes of HPV6 in benign anogenital condylomata is strictly confined to the basal cell layers of the epithelium, which express c‐fos mRNA. This report describes the in situ hybridization analysis of individual mRNA species of HPV6 in 2 malignant tumours. A consistent feature of both carcinomas was the lack of detectable amounts of E6 mRNA, while the E7 mRNA was the major transcript observed. In situ hybridization with a riboprobe for c‐fos revealed an expression pattern similar to that detected with the E7 probe. Hybridization with a probe specific for mRNA with a coding potential for a full‐length E2 protein yielded weak signals in both carcinomas. Using restriction‐enzyme analysis, we compared the long control region of HPV6 amplified by polymerase chain reaction from both tumours with already known HPV6 subtypes. In contrast to previous reports suggesting a correlation between genetic alterations in the long control region of HPV6 and increased malignant behaviour, our data do not support this hypothesis.
Group 3 innate lymphoid cells (ILC3s): Origin, differentiation, and plasticity in humans and mice

Since their discovery, innate lymphoid cells (ILCs) have been the subject of intense research. As their name implies, ILCs are innate cells of lymphoid origin, and can be grouped into subsets based on their cytotoxic activity, cytokine profile, and the transcriptional requirements during ILC differentiation. The main ILC groups are “killer” ILCs, comprising NK cells, and “helper‐like” ILCs (including ILC1s, ILC2s, and ILC3s). This review examines the origin, differentiation stages, and plasticity of murine and human ILC3s. ILC3s express the retinoic acid receptor (RAR) related orphan receptor RORγt and the signature cytokines IL‐22 and IL‐17. Fetal ILC3s or lymphoid tissue inducer cells are required for lymphoid organogenesis, while postnatally developing ILC3s are important for the generation of intestinal cryptopatches and isolated lymphoid follicles as well as for the defence against pathogens and epithelial homeostasis. Here, we discuss the transcription factors and exogenous signals (including cytokines, nutrients and cell‐to‐cell interaction) that drive ILC3 lineage commitment and acquisition of their distinctive effector program.
Investigation in a murine model of possible mechanisms of enhanced local reactions to post-primary diphtheria-tetanus toxoid boosters in recipients of acellular pertussis-diphtheria-tetanus vaccine

In recipients primed with acellular pertussis diphtheria-tetanus combined vaccine (DTaP) an increased incidence of severe local reactions with extensive redness/swelling has been reported for each subsequent dose of diphtheria-tetanus based combination vaccine given as a booster. This has been attributed to residual active pertussis toxin (PT) in the primary vaccine. In this study, we investigated the possible contribution of the A-subunit enzymatic activity and the B-oligomer carbohydrate binding activity of residual PT in DTaP to local reactions in a murine model using Japanese DTaP batches produced before and after the introduction of a test for reversion of pertussis toxoid to toxin. Residual PT activity was correlated with the B-oligomer carbohydrate binding activity. The in vivo mouse footpad swelling model assay indicated that the B-oligomer carbohydrate binding activity and possibly other factors were associated with intensified sensitization to local reaction following diphtheria toxoid booster.
Translational strategies in peripheral neuroinflammation and neurovascular repair

Current therapies for immune-mediated inflammatory disorders in peripheral nerves are non-specific, and partly efficacious. Peripheral nerve regeneration following axonal degeneration or injury is suboptimal, with current therapies focused on modulating the underlying etiology and treating the consequences, such as neuropathic pain and weakness. Despite significant advances in understanding mechanisms of peripheral nerve inflammation, as well as axonal degeneration and regeneration, there has been limited translation into effective new drugs for these disorders. A major limitation in the field has been the unavailability of reliable disease models or research tools that mimic some key essential features of these human conditions. A relatively overlooked aspect of peripheral nerve regeneration has been neurovascular repair required to restore the homeostatic microenvironment necessary for normal function. Using Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) as examples of human acute and chronic immune-mediated peripheral neuroinflammatory disorders respectively, we have performed detailed studies in representative mouse models to demonstrate essential features of the human disorders. These models are important tools to develop and test treatment strategies using realistic outcomes measures applicable to affected patients. In vitro models of the human blood-nerve barrier using endothelial cells derived by endoneurial microvessels provide insights into pro-inflammatory leukocyte-endothelial cell interactions relevant to peripheral neuroinflammation, as well as potential mediators and signaling pathways required for vascular proliferation, angiogenesis, remodeling and tight junction specialization necessary to restore peripheral nerve function following injury. This review discusses some of the progress being made in translational peripheral neurobiology and some future
Efficacy of Intacs Intrastromal Corneal Ring Segment Relative to Depth of Insertion Evaluated with Anterior Segment Optical Coherence Tomography

Aim: To evaluate the effect of implantation depth of Intacs microthin prescription inserts (Addition Technology Inc, Fremont, California) on visual and topographic outcomes in patients with post- laser-assisted in situ keratomileusis (LASIK) ectasias. Settings and Design: Retrospective, observational case series. Materials and Methods: In this case series, 16 eyes of 12 patients were evaluated. All cases were post-LASIK ectasia that had undergone intrastromal corneal ring segment (ICRS) implantation. The planned insertion depth was 70% of stromal thickness using a manual dissector. At least 12 months postoperatively, all eyes underwent Visante (Carl Zeiss Meditec) AS-OCT to determine insertion depth. Cases were categorized into 3 groups based on the measured implantation depth: 40-59% thickness; 60-79% thickness; and ≥80% thickness. Visual, refractive and topographic outcomes were evaluated relative to implantation depth. Results: The lowest improvement in the study parameters ocurred when the implantation depth was ≥80%. In this group, uncorrected visual acuity (UCVA) and best spectacle corrected VA (BSCVA) improved less than 0.5 lines. Manifest refractive spherical equivalent (MRSE) and mean keratometry (Km) change was less than 0.5 diopters (D). The greatest improvements were observed with implantation depth of 60-79% where UCVA and BSCVA increased by 4.5 and 2.5 lines respectively, and MRSE and Km changed by approximately 2.00 D. Less improvement was found when ICRS were implanted between 40-59% of stromal thickness. Conclusion: Implantation of ICRS greater than 80% of stromal thickness may have no effect on visual and topographic status.