Percutaneous flexor digitorum brevis tenotomy: An anatomical study.

INTRODUCTION: A percutaneous selective flexor digitorum brevis (FDB) tenotomy and a proximal interphalangeal (PIP) joint arthrolysis may correct a lesser claw toe deformity keeping flexor digitorum longus (FDL) and active flexion. Our study aimed to verify if the procedure was effective and reliable and if it respects the surrounding soft tissues. MATERIAL AND METHOD: Twelve cadaveric lateral toes were used. A dissection ensured the integrity of both digital nerves, FDL and flexor pulleys and assessed the section of both FDB slips and PIP arthrolysis. RESULTS: A complete section of the two FDB slips was observed in 4 cases (33%). Arthrolysis was achieved in all cases. Surrounding soft tissues were found intact in all cases. CONCLUSION: This procedure is effective regarding PIP arthrolysis, but a technical improvement is required to achieve a reliable section of both FDB slips. In the hands of an experienced surgeon, it has proven to be safe.

Three-dimensional computed tomography analysis and functional results of calcaneal fractures treated by an intramedullary nail.

BACKGROUND: Intramedullary calcaneal nailing is used to treat displaced intra-articular calcaneal fractures. The main goal of the study was to assess the reduction of tomography and secondary goals were patient functional scores and complication rates. METHODS: The functional outcome and restoration of the radiographic parameters were evaluated post-operatively, at three months, at one year, and at the last follow-up. The morphology of the posterior facet was evaluated post-operatively, at one year and at the last follow-up by CTs. RESULTS: Twenty-six patients were included. The mean follow-up was 2.8 years. The mean AOFAS-AHS was 79 at the last follow-up. The mean calcaneal height index and length rose respectively from 0.44 to 0.86 and 83 to 87 mm, and the width decreased from 50 to 46 mm. CONCLUSION: The radiographic parameters were restored. The AOFAS-AHS was comparable with other series. This study confirms the efficiency of this procedure with lower rate of complications.

Exposure assessment of dogs to mycotoxins through consumption of dry feed.

BACKGROUND: The Brazilian exportation of pet food has shown high growth rates in the last two years and determination of the exposure degree is one of the most important parameters for the risk assessment of chemical compounds. In this study the exposure degree of dogs to mycotoxins was estimated and acceptable daily intake (ADI) and safe pet dietary level (SPDL) were calculated. Thus the natural occurrence of fumonisins, zearalenone and aflatoxins was evaluated in 100 dry dog feed samples provided by pet owners in Paraná State, Brazil. RESULTS: Despite the high frequency of fumonisins (68%), zearalenone (95%) and aflatoxins (68%) in feed samples, the mean levels detected were low. ADI for fumonisins and zearalenone was 20.0 and 1.00 µg kg(-1) body weight (BW) day(-1) respectively and SPDL for fumonisins was 2000 µg kg(-1) feed. The probable daily intake values (1.83 µg fumonisins, 0.93 µg zearalenone and 0.02 µg aflatoxins kg(-1) BW day(-1) ) were low. CONCLUSION: The exposure degree of dogs could be assumed to be very low. However, the co-occurrence of these three or other mycotoxins, and possible synergic or additive effects, should be taken into account when determining the maximum allowed levels or risk assessment. © 2016 Society of Chemical Industry.

Monoclonal antibodies specific for the capsid protein of chikungunya virus suitable for multiple applications.

Chikungunya virus (CHIKV) is a mosquito-borne pathogen responsible for epidemics of debilitating arthritic disease. The recent outbreak (2004-2014) resulted in an estimated 1.4-6.5 million cases, with imported cases reported in nearly 40 countries. The development of CHIKV-specific diagnostics and research tools is thus highly desirable. Herein we describe the generation and characterization of the first mAbs specific for the capsid protein (CP) of CHIKV. The antibodies recognized isolates representing the major genotypes of CHIKV, as well as several other alphaviruses, and were reactive in a range of assays including ELISA, Western blot, immunofluorescence and immunohistochemistry (IHC). We have also used the anti-CP mAb 5.5G9 in IHC studies to show that capsid antigen is persistently expressed 30 days post-infection in cells with macrophage morphology in a mouse model of chronic CHIKV disease. These antibodies may thus represent useful tools for further research, including investigations into the structure and function of CHIKV CP, and as valuable reagents for CHIKV detection in a range of settings.

Reduction of ovarian reserve in adult patients with dermatomyositis.

OBJECTIVES: To assess ovarian reserve markers and anti-corpus luteum (anti-CoL) antibodies in dermatomyositis (DM) patients. METHODS: Forty female DM patients were invited to participate. Exclusion criteria included hormonal contraceptive use within the last six months, neoplasia associations, overlapped systemic autoimmune diseases, current pregnancy, gynaecological surgery and individual choice not to participate. The final experimental group for this cross-sectional study included 16 DM patients and 23 healthy controls, each of whom was evaluated during the early follicular phase of the menstrual cycle. Values for IgG anti-CoL (via immunoblotting), follicle stimulating hormone (FSH), estradiol, inhibin B, anti-Müllerian hormone (AMH) serum levels (via ELISA) and sonographic antral follicle count (AFC) were determined. RESULTS: DM patients and controls were of comparable mean age (p>0.05). The mean age of DM onset was 29.1±4.7 years, with disease duration of 5.6±3.2 years. Menstrual cycle characteristics, comorbidity and lifestyle were similar amongst patients in both groups (p>0.05). AMH values of ≤1ng/mL (p=0.027) and AFC values (p=0.017) were significantly reduced in DM patients relative to the control group, whereas serum estradiol levels (p<0.001) were higher in DM patients compared to controls. In contrast, serum FSH and inhibin B levels, ovarian volumes, and anti-CoL antibody frequency were similar in both groups. Differences in AFC and estradiol were determined to be significant following Bonferroni correction for multiple testing. CONCLUSIONS: We identified a diminished ovarian reserve in DM patients of reproductive age. Further studies are necessary to assess the idiopathic inflammatory myopathy-related factors involved in the ovarian impairment of this patient population.

Surgical site infection following isolated lumbar discectomy increases odds of revision lumbar surgery within first 6 months, but not beyond.

BACKGROUND CONTEXT: Lumbar discectomy is a commonly performed surgery following which surgical site infection (SSI) may occur. Prior literature has suggested that, following SSI related to lumbar fusion, the rate of subsequent lumbar surgeries is increased over prolonged periods of time. This has not been studied specifically for lumbar discectomy. PURPOSE: To define factors associated with SSI following lumbar discectomy and determine if subsequently matched cohorts with and without SSI have differential rates of subsequent lumbar surgery beyond irrigation and debridement (I&Ds) over time. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: Adult patients undergoing isolated primary lumbar laminotomy/discectomy were identified from the 2010-2021 M157 PearlDiver database. Exclusion criteria included: age<18 years, preoperative diagnosis of infection, neoplastic, or traumatic diagnoses within 90 days prior to index surgery, additional spinal surgeries on the same day as lumbar discectomy, and not being active in the database for at least 90 days postoperative. From this study population, those who developed SSI were identified based on undergoing I&D within 90 days after surgery. Those with versus without SSI were then matched 1:4 based on age, sex, Elixhauser Comorbidity Index (ECI), and obesity. OUTCOME MEASURES: Following initial I&D, incidence of revision lumbar surgery (revision lumbar discectomy, lumbar laminectomy, lumbar fusion) out to 5 years after lumbar discectomy. METHODS: Following index isolated lumbar discectomy, those with versus without SSI requiring I&D were matched and compared for incidence of secondary surgery in defined time intervals (0-6 months, 6-12 months, 1-2 years, 2-5 years) using multivariable logistic regression, controlling for patient age, sex, ECI, and obesity status. RESULTS: Of 323,025 isolated lumbar discectomy patients, SSI requiring I&D was identified for 583 (0.18%). Multivariable analysis revealed several independent predictors of these SSIs: younger age (odds ratio [OR] 0.85 per decade increase), ECI (OR 1.22 per 2-point increase), and obesity (OR 1.30). Following matching of those with versus without SSI requiring I&D, rates of subsequent surgery beyond I&D were compared. Those with SSI had significantly increased odds of lumbar revision in the first six months (OR 5.26, p<.001), but not 6-12 months (p=.462), 1-2 years (p=.515), or 2-5 years (p=.677). CONCLUSIONS: Overall, SSI requiring I&D is a rare postoperative complication following lumbar discectomy. If occurring, subsequent surgery beyond I&D was higher in the first 6 months, but then not increased at subsequent time points out to five years.

Comparing Perioperative Outcomes of Total Intravenous Anesthesia (TIVA) With Volatile Anesthesia in Patients With Obesity: A Systematic Review.

In this systematic review, the perioperative outcomes of total intravenous anesthesia (TIVA) and volatile anesthesia were compared in obese adults (BMI ≥ 30 kg/m²) undergoing elective surgery. The review analyzed data from 12 randomized-controlled trials involving 935 patients, sourced from PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Cochrane, Scopus, and Web of Science databases. The focus was on intraoperative vital signs, emergence time, postoperative nausea and vomiting (PONV), duration of post-anesthesia care unit (PACU) stay, and ICU admission rates. Findings showed that TIVA (using propofol) might reduce PONV, but there were no significant differences in other outcomes compared to volatile anesthesia (with desflurane as the most common agent). The review highlights the need for more research, especially comparing sevoflurane with TIVA, to establish clear clinical guidelines for anesthesia in obese patients.

Nutritional Deficiencies Before and After Bariatric Surgery in Low- and High-Income Countries: Prevention and Treatment.

Nutritional deficiencies represent a prevalent concern among individuals with obesity, stemming from suboptimal dietary habits, chronic inflammation, and preoperative weight reduction efforts. Bariatric surgical interventions, employing either restrictive, malabsorptive or a combination of the two methods, further compound these deficiencies. Commonly observed nutritional deficits following bariatric surgeries include vitamin B12, vitamin D, thiamine, folate, iron, and protein deficiencies. These deficiencies are further complicated by disparities in healthcare resources and income that distinguish low, medium, and high-income countries. The escalating rates of obesity in low- and medium-income countries are primarily attributed to the increasing availability of cheap, nutritionally depleted, and processed foods, coupled with limited access to healthcare. The provision of bariatric surgical interventions in such regions is hindered by the lack of appropriately trained medical personnel and adequate infrastructure. Additionally, the crucial facets of postoperative care, including diligent follow-up, precise weight loss monitoring, and the administration of appropriate nutritional supplements, often remain lacking. This narrative review provides a comprehensive examination of the prevention and treatment of nutritional deficiencies before and after bariatric surgery in the context of varying healthcare resources and income levels. Bariatric procedures and their global prevalence are discussed, and the prevalence, symptoms, and management strategies of specific nutritional deficiencies are explained. This review also outlines practical strategies for providing more equitable care in low- and medium-income countries.

Development of a value-based healthcare burns core set for adult burn care.

BACKGROUND: Value-based healthcare (VBHC) is increasingly implemented in healthcare worldwide. Transparent measurement of the outcomes most important and relevant to patients is essential in VBHC, which is supported by a core set of most important quality indicators and outcomes. Therefore, the aim of this study was to develop a VBHC-burns core set for adult burn patients. METHODS: A three-round modified national Delphi study, including 44 outcomes and 24 quality indicators, was conducted to reach consensus among Dutch patients, burn care professionals and researchers. Items were rated on a nine-point Likert scale and selected if ≥ 70% in each group considered an item 'important'. Subsequently, instruments quantifying selected outcomes were identified based on a literature review and were chosen in a consensus meeting using recommendations from the Dutch consensus-based standard set and the Dutch Centre of Expertise on Health Disparities. Time assessment points were chosen to reflect the burn care and patient recovery process. Finally, the initial core set was evaluated in practice, leading to the adapted VBHC-burns core set. RESULTS: Twenty-seven patients, 63 burn care professionals and 23 researchers participated. Ten outcomes and four quality indicators were selected in the Delphi study, including the outcomes pain, wound healing, physical activity, self-care, independence, return to work, depression, itching, scar flexibility and return to school. Quality indicators included shared decision-making (SDM), the number of patients receiving aftercare, determination of burn depth, and assessment of active range of motion. After evaluation of its use in clinical practice, the core set included all items except SDM, which are assessed by 9 patient-reported outcome instruments or measured in clinical care. Assessment time points included are at discharge, 2 weeks, 3 months, 12 months after discharge and annually afterwards. CONCLUSION: A VBHC-burns core set was developed, consisting of outcomes and quality indicators that are important to burn patients and burn care professionals. The VBHC-burns core set is now systemically monitored and analysed in Dutch burn care to improve care and patient relevant outcomes. As improving burn care and patient relevant outcomes is important worldwide, the developed VBHC-burns core set could be inspiring for other countries.

Neutralizing monoclonal antibodies to the E2 protein of chikungunya virus protects against disease in a mouse model.

Chikungunya virus (CHIKV) recently caused the largest epidemic ever recorded for this virus involving an estimated 1.4-6.5million cases, with imported cased reported in over 40 countries. The number of monoclonal antibodies specific for this re-emerging alphavirus is currently limited. Herein we describe the generation and characterisation of five monoclonal antibodies specific for the E2 glycoprotein of CHIKV. The antibodies detected a range of CHIKV isolates in several assays including ELISA, Western blot, immunofluorescence assay (IFA) and immunohistochemistry (IHC) without evidence of cross-reactivity with other alphaviruses. Four antibodies also neutralised CHIKV in vitro, two of which provided complete protection against arthritis in a CHIKV mouse model when administered prior to infection. Given the current shortage of widely available reagents for CHIKV, these specific antibodies will be useful not only in research, but may also provide the basis for new diagnostics and treatments.

Percutaneous arthroscopically assisted cheilectomy combined to percutaneous proximal phalanx osteotomy in hallux rigidus: Clinical and radiological outcomes in 30 feet at a 48-month follow-up.

BACKGROUND: Hallux rigidus is a degenerative condition affecting the middle age population. It affects patients by limiting their first metatarsophalangeal range of motion (ROM) and also, their shoe wear. The objective of our work was to present an original operative technique which preserves the native joint and improves pain with minimal complications. METHODS: We conducted a retrospective multicenter cohort study of 28 patients (30 feet) suffering from moderate hallux rigidus, operated between October 2010 and October 2017 with at least 48months of follow-up. Clinical and radiological assessments included pre- and postoperative ROM, the American Orthopedic Foot and Ankle Society (AOFAS) score and forefoot radiological evaluation. No patients were lost to follow-up. RESULTS: The mean AOFAS score increased from 59 (range, 51 to 67) preoperatively to 84 (range, 80 to 88) at final follow-up. A total of 37 patients (97%) were satisfied. From a ROM point of view, this remained relatively unchanged between preoperative and postoperative values. CONCLUSION: The percutaneous arthroscopically assisted cheilectomy combined with a percutaneous proximal phalanx osteotomy, significantly improves pain in hallux rigidus with index minus in patients with Coughlin stage I and II after a mean of 4-year follow-up. LEVEL OF EVIDENCE: IV.

Dynamic top-down biasing implements rapid adaptive changes to individual movements.

Complex behaviors depend on the coordinated activity of neural ensembles in interconnected brain areas. The behavioral function of such coordination, often measured as co-fluctuations in neural activity across areas, is poorly understood. One hypothesis is that rapidly varying co-fluctuations may be a signature of moment-by-moment task-relevant influences of one area on another. We tested this possibility for error-corrective adaptation of birdsong, a form of motor learning which has been hypothesized to depend on the top-down influence of a higher-order area, LMAN (lateral magnocellular nucleus of the anterior nidopallium), in shaping moment-by-moment output from a primary motor area, RA (robust nucleus of the arcopallium). In paired recordings of LMAN and RA in singing birds, we discovered a neural signature of a top-down influence of LMAN on RA, quantified as an LMAN-leading co-fluctuation in activity between these areas. During learning, this co-fluctuation strengthened in a premotor temporal window linked to the specific movement, sequential context, and acoustic modification associated with learning. Moreover, transient perturbation of LMAN activity specifically within this premotor window caused rapid occlusion of pitch modifications, consistent with LMAN conveying a temporally localized motor-biasing signal. Combined, our results reveal a dynamic top-down influence of LMAN on RA that varies on the rapid timescale of individual movements and is flexibly linked to contexts associated with learning. This finding indicates that inter-area co-fluctuations can be a signature of dynamic top-down influences that support complex behavior and its adaptation.

Precision-activated T-cell engagers targeting HER2 or EGFR and CD3 mitigate on-target, off-tumor toxicity for immunotherapy in solid tumors.

To enhance the therapeutic index of T-cell engagers (TCEs), we engineered masked, precision-activated TCEs (XPAT proteins), targeting a tumor antigen (human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR)) and CD3. Unstructured XTEN polypeptide masks flank the N and C termini of the TCE and are designed to be released by proteases in the tumor microenvironment. In vitro, unmasked HER2-XPAT (uTCE) demonstrates potent cytotoxicity, with XTEN polypeptide masking providing up to 4-log-fold protection. In vivo, HER2-XPAT protein induces protease-dependent antitumor activity and is proteolytically stable in healthy tissues. In non-human primates, HER2-XPAT protein demonstrates a strong safety margin (>400-fold increase in tolerated maximum concentration versus uTCE). HER2-XPAT protein cleavage is low and similar in plasma samples from healthy and diseased humans and non-human primates, supporting translatability of stability to patients. EGFR-XPAT protein confirmed the utility of XPAT technology for tumor targets more widely expressed in healthy tissues.

Average 4-Year Outcomes of Distal Oblique First Metatarsal Osteotomy for Stage 1 to 3 Hallux Rigidus.

BACKGROUND: Hallux rigidus is the second most frequent pathology of the first ray. Surgical options for degenerative metatarsophalangeal joint disease are either joint destructive or conservative procedures. The hypothesis was that oblique distal shortening osteotomy of the first metatarsal is an effective conservative technique for the management of stage 1 to 3 hallux rigidus. METHODS: We conducted a retrospective cohort study of 87 feet with Coughlin and Shurnas's stage 1-3 hallux rigidus, operated between 2009 and 2019. The cohort consisted in 72 patients (87 feet) with an average age of 57±9 (30/79) years; 22 of 87 (25.3%) feet had the first metatarsal surgery performed in isolation; 65 of 87 (74.7%) had concomitant forefoot procedures, including 31 of 87 (35.6%) with Akin phalangeal osteotomies and 34 of 87 (39.1%) with Moberg phalangeal osteotomies.We evaluated the American Orthopaedic Foot & Ankle Society (AOFAS) Scale, subjective satisfaction, joint amplitudes, shortening rate, and occurrence of postoperative complications with a mean follow-up of 51 months (16/134). RESULTS: The AOFAS score increased from 54.2±11.3 (25/70) preoperatively to 92.2±7.8 (62/100) postoperatively (P < .001). Patients reported excellent or good outcome in 95.4% of cases. The 40-point self-reported pain subscale score improved from 19.6 (± 10.0) to 37.4 (± 5.4), P < .001.The overall range of motion increased from 61±21 (20/110) degrees to 69±17 (35/120) degrees (P < .001). The mean first metatarsal shortening rate (SRpo) was 9.6%. Neither the Coughlin grade, the metatarsal index, or the SRpo influenced the AOFAS score. At 6-month follow-up, 15 patients had transfer metatarsalgia compared with 5 at last follow-up without requiring another surgical procedure. The risk was not significantly different according to Coughlin's stage, preoperative metatarsal index, or SRpo. CONCLUSION: Oblique distal osteotomy of the first metatarsal for stage 1-3 hallux rigidus, often in combination with other first ray procedures, performed well during our follow-up time period, with a high subjective satisfaction rate and few complications. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Songbirds can learn flexible contextual control over syllable sequencing.

The flexible control of sequential behavior is a fundamental aspect of speech, enabling endless reordering of a limited set of learned vocal elements (syllables or words). Songbirds are phylogenetically distant from humans but share both the capacity for vocal learning and neural circuitry for vocal control that includes direct pallial-brainstem projections. Based on these similarities, we hypothesized that songbirds might likewise be able to learn flexible, moment-by-moment control over vocalizations. Here, we demonstrate that Bengalese finches (Lonchura striata domestica), which sing variable syllable sequences, can learn to rapidly modify the probability of specific sequences (e.g. 'ab-c' versus 'ab-d') in response to arbitrary visual cues. Moreover, once learned, this modulation of sequencing occurs immediately following changes in contextual cues and persists without external reinforcement. Our findings reveal a capacity in songbirds for learned contextual control over syllable sequencing that parallels human cognitive control over syllable sequencing in speech.

Human speech and birdsong share numerous parallels. Both humans and birds learn their vocalizations during critical phases early in life, and both learn by imitating adults. Moreover, both humans and songbirds possess specific circuits in the brain that connect the forebrain to midbrain vocal centers. Humans can flexibly control what they say and how by reordering a fixed set of syllables into endless combinations, an ability critical to human speech and language. Birdsongs also vary depending on their context, and melodies to seduce a mate will be different from aggressive songs to warn other males to stay away. However, so far it was unclear whether songbirds are also capable of modifying songs independent of social or other naturally relevant contexts. To test whether birds can control their songs in a purposeful way, Veit et al. trained adult male Bengalese finches to change the sequence of their songs in response to random colored lights that had no natural meaning to the birds. A specific computer program was used to detect different variations on a theme that the bird naturally produced (for example, "ab-c" versus "ab-d"), and rewarded birds for singing one sequence when the light was yellow, and the other when it was green. Gradually, the finches learned to modify their songs and were able to switch between the appropriate sequences as soon as the light cues changed. This ability persisted for days, even without any further training. This suggests that songbirds can learn to flexibly and purposefully modify the way in which they sequence the notes in their songs, in a manner that parallels how humans control syllable sequencing in speech. Moreover, birds can learn to do this 'on command' in response to an arbitrarily chosen signal, even if it is not something that would impact their song in nature. Songbirds are an important model to study brain circuits involved in vocal learning. They are one of the few animals that, like humans, learn their vocalizations by imitating conspecifics. The finding that they can also flexibly control vocalizations may help shed light on the interactions between cognitive processing and sophisticated vocal learning abilities.

Adrenal steroidogenesis and ovarian reserve in adult childhood-onset systemic lupus erytematosus patients.

OBJECTIVE: To assess overall adrenal mineralocorticoid/glucocorticoid/androgen steroidogenesis in childhood-onset systemic lupus erythematosus (cSLE) patients and the possible effect of prednisone on adrenal hormones and ovarian reserve. METHODS: Fifty-one adult cSLE (ACR criteria) patients and 23 healthy controls were evaluated for adrenal steroidogenesis including mineralocorticoid (progesterone, deoxycorticosterone, aldosterone), glucocorticoid (17-OHprogesterone, 11-desoxycortisol, cortisol), and androgen (dehydroepiandrosterone-sulfate, androstenedione, total testosterone, and dihydrotestosterone) hormones. Ovarian reserve assessment included follicle-stimulating hormone (FSH), estradiol, anti-Müllerian hormone, ovarian volumes, and antral follicle count. RESULTS: The median of current age [29.11 (19-39.8) vs. 30.8 (19.6-42.1) years, p = 0.502] was similar in adult cSLE and controls. Regarding mineralocorticoid/glucocorticoid, the median of progesterone (p = 0.003), 17-OH progesterone (p < 0.001), and 11-desoxycortisol (p = 0.036) were significantly lower in patients compared to controls. All androgen steroidogenesis hormones were reduced in the former group [dehydroepiandrosterone-sulfate (p < 0.001), androstenedione (p = 0.001), total testosterone (p = 0.005), and dihydrotestosterone (p < 0.001)]. Further comparison of patients with and without current use of prednisone and controls revealed a predominant impact on adrenal glucocorticoid and androgen steroidogenesis with reduced levels of 17-OH progesterone [0.17 (0-0.5) vs. 0.27 (0.1-2.9) vs. 0.33 (0.1-0.8) ng/mL, p < 0.001], dehydroepiandrosterone-sulfate [0.155 (0-0.6) vs. 0.49 (0.1-1.6) vs. 1.11 (0.1-2.6) µg/mL, p < 0.001], androstenedione [0.56 (0.2-4.4) vs. 1.7 (0.5-4.5) vs. 2.33 (0.3-3.8) ng/mL, p < 0.001], total testosterone [12 (12-167) vs. 16 (12-28) vs. (16.5 (0-50) ng/d, p = 0.002], and dihydrotestosterone [92.68 (11.8-198.5) vs. 160.62 (37.9-842.1) vs. 188.3 (71.3-543.9) pg/ml, p < 0.001] in patients under this drug. In addition, patients with this therapy had reduced median ovarian volumes [4.14 (2-12) vs. 7.13 (2-25.7) vs. 5.18 (2.4-17.3) cm3, p = 0.028) that was not associated with cyclophosphamide cumulative dose (p > 0.05). The median prednisone dose was 15/mg/day (2.5-40). CONCLUSIONS: We provided novel evidence that cSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. Furthermore, low/moderate prednisone use seems to underlie these abnormalities and may also adversely affect ovarian reserve, independently of immunosuppressants. Key Points • cSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. • Low/moderate prednisone use may affect ovarian reserve, independently of immunosuppressants.

Nanopatch-targeted skin vaccination against West Nile Virus and Chikungunya virus in mice.

The 'Nanopatch' (NP) comprises arrays of densely packed projections with a defined geometry and distribution designed to physically target vaccines directly to thousands of epidermal and dermal antigen presenting cells (APCs). These miniaturized arrays are two orders of magnitude smaller than standard needles-which deliver most vaccines-and are also much smaller than current microneedle arrays. The NP is dry-coated with antigen, adjuvant, and/or DNA payloads. After the NP was pressed onto mouse skin, a protein payload co-localized with 91.4 + or - 4.1 APC mm(-2) (or 2925 in total) representing 52% of the delivery sites within the NP contact area, agreeing well with a probability-based model used to guide the device design; it then substantially increases as the antigen diffuses in the skin to many more cells. APC co-localizing with protein payloads rapidly disappears from the application area, suggesting APC migration. The NP also delivers DNA payloads leading to cutaneous expression of encoded proteins within 24 h. The efficiency of NP immunization is demonstrated using an inactivated whole chikungunya virus vaccine and a DNA-delivered attenuated West Nile virus vaccine. The NP thus offers a needle-free, versatile, highly effective vaccine delivery system that is potentially inexpensive and simple to use.

The relation between biological activity of the rain forest and mineral composition of soils.

In most soils of the humid tropics, kaolinitic topsoil horizons overlie more gibbsitic horizons. This arrangement cannot be produced simply by leaching. Quantitative measurement of the turnover of chemical elements in the litterfall in an Amazonian ecosystem indicates that the forest cycles a significant amount of elements, particularly silicon. As a result, fluids that percolate through topsoil horizons already contain dissolved silicon. This effect keeps silicon from being leached down and may account for the stability of kaolinite in the soil upper horizons. The soil mineral composition is thus maintained by biological activity.

Tracing of dissolved organic matter from the Sepetiba Bay (Brazil) by PARAFAC analysis of total luminescence matrices.

Fluorescent excitation-emission matrices (FEEM) of the fluorescent dissolved organic matter (FDOM) are widely used for DOM characterization and tracing. In this work, a set of FEEM from sampling campaigns in the Sepetiba Bay (Brazil) was decomposed into independent components using the parallel factor analysis (PARAFAC) algorithm. Four independent components were extracted describing the total fluorescence of the FDOM. The well described peaks A, C, M, B and T were found, and a new peak, A', linked to the C peak, was detected. Relative contribution of each of four components to the total fluorescence confirms that the coastal water has DOM of terrestrial origin, except for the 275Ex/400-500Em range (nm), which primarily occurs in marine waters.

Discrete Circuits Support Generalized versus Context-Specific Vocal Learning in the Songbird.

Motor skills depend on the reuse of individual gestures in multiple sequential contexts (e.g., a single phoneme in different words). Yet optimal performance requires that a given gesture be modified appropriately depending on the sequence in which it occurs. To investigate the neural architecture underlying such context-dependent modifications, we studied Bengalese finch song, which, like speech, consists of variable sequences of "syllables." We found that when birds are instructed to modify a syllable in one sequential context, learning generalizes across contexts; however, if unique instruction is provided in different contexts, learning is specific for each context. Using localized inactivation of a cortical-basal ganglia circuit specialized for song, we show that this balance between generalization and specificity reflects a hierarchical organization of neural substrates. Primary motor circuitry encodes a core syllable representation that contributes to generalization, while top-down input from cortical-basal ganglia circuitry biases this representation to enable context-specific learning.