Esr1+ hypothalamic-habenula neurons shape aversive states.

Excitatory projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) drive aversive responses. We used patch-sequencing (Patch-seq) guided multimodal classification to define the structural and functional heterogeneity of the LHA-LHb pathway. Our classification identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles and projection patterns. We found that genetically defined LHA-LHb neurons signal distinct aspects of emotional or naturalistic behaviors, such as estrogen receptor 1-expressing (Esr1+) LHA-LHb neurons induce aversion, whereas neuropeptide Y-expressing (Npy+) LHA-LHb neurons control rearing behavior. Repeated optogenetic drive of Esr1+ LHA-LHb neurons induces a behaviorally persistent aversive state, and large-scale recordings showed a region-specific neural representation of the aversive signals in the prelimbic region of the prefrontal cortex. We further found that exposure to unpredictable mild shocks induced a sex-specific sensitivity to develop a stress state in female mice, which was associated with a specific shift in the intrinsic properties of bursting-type Esr1+ LHA-LHb neurons. In summary, we describe the diversity of LHA-LHb neuron types and provide evidence for the role of Esr1+ neurons in aversion and sexually dimorphic stress sensitivity.

Histone variant HTB4 delays leaf senescence by epigenetic control of Ib bHLH transcription factor-mediated iron homeostasis.

Leaf senescence is an orderly process regulated by multiple internal factors and diverse environmental stresses including nutrient deficiency. Histone variants are involved in regulating plant growth and development. However, their functions and underlying regulatory mechanisms in leaf senescence remain largely unclear. Here, we found that H2B histone variant HTB4 functions as a negative regulator of leaf senescence. Loss of function of HTB4 led to early leaf senescence phenotypes that were rescued by functional complementation. RNA-seq analysis revealed that several Ib subgroup basic helix-loop-helix (bHLH) transcription factors (TFs) involved in iron (Fe) homeostasis, including bHLH038, bHLH039, bHLH100, and bHLH101, were suppressed in the htb4 mutant, thereby compromising the expressions of FERRIC REDUCTION OXIDASE 2 (FRO2) and IRON-REGULATED TRANSPORTER (IRT1), two important components of the Fe uptake machinery. Chromatin immunoprecipitation-quantitative polymerase chain reaction analysis revealed that HTB4 could bind to the promoter regions of Ib bHLH TFs and enhance their expression by promoting the enrichment of the active mark H3K4me3 near their transcriptional start sites. Moreover, overexpression of Ib bHLH TFs or IRT1 suppressed the premature senescence phenotype of the htb4 mutant. Our work established a signaling pathway, HTB4-bHLH TFs-FRO2/IRT1-Fe homeostasis, which regulates the onset and progression of leaf senescence.

Multiple Perianal Epidermal Cysts Found in a Case of Lowe Syndrome: A Case Report and Review of the Literature.

BACKGROUND Lowe syndrome, also known as oculocerebrorenal syndrome, is a rare genetic condition caused by an X-linked mutation of the OCRL1 gene, with an estimated prevalence in the general population of approximately 1 in 500 000. It is a multisystem disorder most commonly affecting the eyes, central nervous system, and kidneys. These commonly manifest as congenital cataracts, intellectual disability, and proximal renal dysfunction (Fanconi-type). Epidermal lesions are an uncommon manifestation of this condition, and the association is not completely understood. CASE REPORT Here we present a case of a 9-year-old boy with Lowe syndrome who presented with multiple cystic masses found in the perianal region. An excision was then performed to remove the masses and found that the lesions were epidermal cysts, which are infrequently found in Lowe syndrome. After excision, the patient recovered uneventfully without complications. CONCLUSIONS While epidermal cysts are an uncommon manifestation that have been documented, our case remains unique given the location and associated symptoms of the lesions. At presentation, the constellation of pain and perianal masses was concerning for a malignant etiology. However, after diagnostic imaging was performed, these lesions were found to be epidermal cysts, an infrequent manifestation of Lowe syndrome. Few previous case reports described cystic lesions in association with Lowe syndrome, and none, to our knowledge, have described multiple symptomatic perianal lesions. This case is important to consider because epidermal cystic lesions can be found with this presentation and should be considered on differential diagnoses for dermatologic findings in Lowe syndrome patients.

A 12-Year-Old Girl with Juvenile Granulosa Cell Tumor of the Ovary, Presenting with Adolescent Hyperprolactinemia, Galactorrhea, and Amenorrhea.

BACKGROUND Juvenile-type granulosa cell tumors (JGCTs) are a rare subtype of sex cord stromal tumor with a characteristic histology that is commonly found in the first 3 decades of life. It most commonly presents with symptoms of hyperestrogenism, which may present as precocious pseudopuberty or as menstruation-related symptoms, allowing for early detection of the tumor. CASE REPORT We present the case of a 12-year-old girl who presented to her primary care provider (PCP) with secondary amenorrhea with intermittent abdominal pain, who underwent an ultrasound for further evaluation, which revealed a large incidental pelvic mass. She was admitted to the Emergency Department (ED) and had findings of galactorrhea and hyperprolactinemia on examination. Imaging studies demonstrated a large ovarian mass measuring 15.0×9.0×18.8 cm that was resected, and subsequent pathology results showed JGCT stage 1A. CONCLUSIONS Prognosis of granulosa cell tumors (GCT) largely depends on its initial size, stage at diagnosis, residual tumors after surgery, and the subtype of GCT. If the patient is of reproductive age, fertility-sparing surgical options must be considered and patients must be regularly monitored for recurrence. JGCTs can present with minimal to no symptoms of precocious puberty in young girls but may present with amenorrhea, which may be considered normal for their developmental age. Although JGCTs are rare, they are important to include in differential diagnoses of younger female patients with abdominal pain, especially if accompanied by hormonal irregularities.

N-p-Conductor Transition of Gas Sensing Behaviors in Mo2CTx MXene.

It is highly important to implement various semiconducting, such as n- or p-type, or conducting types of sensing behaviors to maximize the selectivity of gas sensors. To achieve this, researchers so far have utilized the n-p (or p-n) two-phase transition using doping techniques, where the addition of an extra transition phase provides the potential to greatly increase the sensing performance. Here, we report for the first time on an n-p-conductor three-phase transition of gas sensing behavior using Mo2CTx MXene, where the presence of organic intercalants and film thickness play a critical role. We found that 5-nm-thick Mo2CTx films with a tetramethylammonium hydroxide (TMAOH) intercalant displayed a p-type gas sensing response, while the films without the intercalant displayed a clear n-type response. Additionally, Mo2CTx films with thicknesses over 700 nm exhibited a conductor-type response, unlike the thinner films. It is expected that the three-phase transition was possible due to the unique and simultaneous presence of the intrinsic metallic conductivity and the high-density of surface functional groups of the MXene. We demonstrate that the gas response of Mo2CTx films containing tetramethylammonium (TMA) ions toward volatile organic compounds (VOCs), NH3, and NO2 is ∼30 times higher than that of deintercalated films, further showing the influence of intercalants on sensing performance. Also, DFT calculations show that the adsorption energy of NH3 and NO2 on Mo2CTx shifts from -0.973, -1.838 eV to -1.305, -2.750 eV, respectively, after TMA adsorption, demonstrating the influence of TMA in enhancing sensing performance.

Ethylene responsive factor34 mediates stress-induced leaf senescence by regulating salt stress-responsive genes.

Leaf senescence proceeds with age but is modulated by various environmental stresses and hormones. Salt stress is one of the most well-known environmental stresses that accelerate leaf senescence. However, the molecular mechanisms that integrate salt stress signalling with leaf senescence programmes remain elusive. In this study, we characterised the role of ETHYLENE RESPONSIVE FACTOR34 (ERF34), an Arabidopsis APETALA2 (AP2)/ERF family transcription factor, in leaf senescence. ERF34 was differentially expressed under various leaf senescence-inducing conditions, and negatively regulated leaf senescence induced by age, dark, and salt stress. ERF34 also promoted salt stress tolerance at different stages of the plant life cycle such as seed germination and vegetative growth. Transcriptome analysis revealed that the overexpression of ERF34 increased the transcript levels of salt stress-responsive genes including COLD-REGULATED15A (COR15A), EARLY RESPONSIVE TO DEHYDRATION10 (ERD10), and RESPONSIVE TO DESICCATION29A (RD29A). Moreover, ERF34 directly bound to ERD10 and RD29A promoters and activated their expression. Our findings indicate that ERF34 plays a key role in the convergence of the salt stress response with the leaf senescence programmes, and is a potential candidate for crop improvement, particularly by enhancing salt stress tolerance.

Machine Learning Models That Integrate Tumor Texture and Perfusion Characteristics Using Low-Dose Breast Computed Tomography Are Promising for Predicting Histological Biomarkers and Treatment Failure in Breast Cancer Patients.

This prospective study enrolled 147 women with invasive breast cancer who underwent low-dose breast CT (80 kVp, 25 mAs, 1.01-1.38 mSv) before treatment. From each tumor, we extracted eight perfusion parameters using the maximum slope algorithm and 36 texture parameters using the filtered histogram technique. Relationships between CT parameters and histological factors were analyzed using five machine learning algorithms. Performance was compared using the area under the receiver-operating characteristic curve (AUC) with the DeLong test. The AUCs of the machine learning models increased when using both features instead of the perfusion or texture features alone. The random forest model that integrated texture and perfusion features was the best model for prediction (AUC = 0.76). In the integrated random forest model, the AUCs for predicting human epidermal growth factor receptor 2 positivity, estrogen receptor positivity, progesterone receptor positivity, ki67 positivity, high tumor grade, and molecular subtype were 0.86, 0.76, 0.69, 0.65, 0.75, and 0.79, respectively. Entropy of pre- and postcontrast images and perfusion, time to peak, and peak enhancement intensity of hot spots are the five most important CT parameters for prediction. In conclusion, machine learning using texture and perfusion characteristics of breast cancer with low-dose CT has potential value for predicting prognostic factors and risk stratification in breast cancer patients.

Regulation of autophagy by controlling Erk1/2 and mTOR for platelet-derived growth factor-BB-mediated vascular smooth muscle cell phenotype shift.

AIMS: Vascular smooth muscle cell (VSMC) phenotype shift is involved in the pathophysiology of vascular injury or platelet-derived growth factor (PDGF)-induced abnormal proliferation and migration of VSMCs. We aimed to investigate the underlying mechanism involved in PDGF-mediated signaling pathways and autophagy regulation followed by VSMC phenotype shift. MAIN METHODS: The proliferation, migration and apoptosis of cultured rat aortic VSMCs were measured, and cells undergoing phenotype shift and autophagy were examined. Specific inhibitors for target proteins in signaling pathways were applied to clarify their roles in regulating cell functions. KEY FINDINGS: PDGF-BB stimulation initiated autophagy activation and synthetic phenotype transition by decreasing α-smooth muscle-actin (SMA), calponin and myosin heavy chain (MHC) and increasing osteopontin (OPN) expression. However, U0126, a potent extracellular signal-regulated kinase 1/2 (Erk1/2) inhibitor, decreased PDGF-BB-induced LC3 expression, while rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), increased it. Furthermore, U0126 decreased the expresseion of autophagy-related genes (Atgs) such as beclin-1, Atg7, Atg5, and Atg12-Atg5 complex, indicating that Erk1/2 is a regulator of PDGF-BB-induced VSMC autophagy. Regardless of autophagy inhibition by U0126 or activation by rapamycin, the PDGF-BB-induced decrease in SMA, calponin and MHC and increase in OPN expression were inhibited. Furthermore, PDGF-BB-stimulated VSMC proliferation, migration and proliferating cell nuclear antigen (PCNA) expression were inhibited by U0126 and rapamycin. SIGNIFICANCE: These findings suggest that PDGF-BB-induced autophagy is strongly regulated by Erk1/2, an mTOR-independent pathway, and any approach for targeting autophagy modulation is a potential therapeutic strategy for addressing abnormal VSMC proliferation and migration.

Sodium propionate exerts anticancer effect in mice bearing breast cancer cell xenograft by regulating JAK2/STAT3/ROS/p38 MAPK signaling.

Propionate is a short-chain fatty acid (SCFA) mainly produced from carbohydrates by gut microbiota. Sodium propionate (SP) has shown to suppress the invasion in G protein-coupled receptor 41 (GPR41) and GPR43-overexpressing breast cancer cells. In this study we investigated the effects of SP on the proliferation, apoptosis, autophagy, and antioxidant production of breast cancer cells. We showed that SP (5-20 mM) dose-dependently inhibited proliferation and induced apoptosis in breast cancer cell lines JIMT-1 (ER-negative and HER2-expressing) and MCF7 (ER-positive type), and this effect was not affected by PTX, thus not mediated by the GPR41 or GPR43 SCFA receptors. Meanwhile, we demonstrated that SP treatment increased autophagic and antioxidant activity in JIMT-1 and MCF7 breast cancer cells, which might be a compensatory mechanism to overcome SP-induced apoptosis, but were not sufficient to overcome SP-mediated suppression of proliferation and induction of apoptosis. We revealed that the anticancer effect of SP was mediated by inhibiting JAK2/STAT3 signaling which led to cell-cycle arrest at G0/G1 phase, and increasing levels of ROS and phosphorylation of p38 MAPK which induced apoptosis. In nude mice bearing JIMT-1 and MCF7 cells xenograft, administration of SP (20 mg/mL in drinking water) significantly suppressed tumor growth by regulating STAT3 and p38 in tumor tissues. These results suggest that SP suppresses proliferation and induces apoptosis in breast cancer cells by inhibiting STAT3, increasing the ROS level and activating p38. Therefore, SP is a candidate therapeutic agent for breast cancer.

Outcome of nonoperative treatment for hip fractures in elderly patients: A systematic review of recent literature.

Many studies have shown that surgical management still leads to the best outcomes in elderly patients with hip fractures, with some studies showing non-inferiority of nonsurgical management as compared to surgery in fragility fractures. Evidence-based guidelines on whether to operate on these patients are lacking. A systematic literature search was conducted regarding outcomes of nonoperatively treated hip fractures in elderly patients with various comorbidities. A structured literature review of multiple databases (PubMed, Web of Science, EMBASE, and Cochrane library) referenced articles from 2000 to 2020. A total of 596 patients from 11 published studies were identified. Mean age was 83.3 years. Overall 328 (69.7%) complications occurred in 470 patients with nonsurgical treatment. Pneumonia and urinary tract infections were the most common complications which occurred in 53 (16.1%) and 46 (14.0%) patients, respectively. Hip fracture patients who were treated nonoperatively had a higher in-hospital (17.1% vs. 4.4%; p < 0.001), 30-day (31.4% vs. 10.2%; p < 0.001), and 1-year (48.5% vs. 19.9%; p < 0.001) mortality compared to a matched group of operatively treated patients (n = 1464). Of the 110 patients whose reported cause of death was nonoperative care, 44 (40%) was due to pneumonia. Patients with nonoperative treatment following hip fracture were associated with substantially higher complication and mortality compared with patients who were treated operatively. Our study will help health-care providers and caregivers to enable more informed decision-making for families and patients confronted with a hip fracture.

Complications after internal screw fixation of nondisplaced femoral neck fractures in elderly patients: A systematic review.

OBJECTIVE: Internal fixation with cannulated screws for nondisplaced femoral neck fractures in the elderly has substantial reoperation and mortality rates. The selection of either internal fixation or arthroplasty for nondisplaced femoral neck fracture is debatable. METHODS: We performed a systematic review of the literature regarding complications in the internal fixation of nondisplaced femoral neck fractures in elderly (>60 years old) patients. We searched in multiple databases (PubMed, Web of Science, Embase, and Cochrane Library) for articles in this area; there was no limitation over the publication year. RESULTS: A total of 1971 patients were identified from 16 published studies. All these patients were over 60 years old. The minimum follow-up after the surgical procedure was 11 months (range: 11-183 months). A total of 329 fractures (16.7%) with radiographic and clinical failures after fixation were identified with regard to stable femoral neck fractures. The single most common complication after surgery was nonunion (129/329), with a pooled percentage of 39.2%. Osteonecrosis was found to be the second most common cause of revision surgery (31.9%). The overall reoperation rate attributable to surgical complications was 15.2% (300/1971 patients). Conversion to hip arthroplasty was performed in 244 patients (12.4%) after primary fixation. CONCLUSION: Our study elucidated further the complication rate of nondisplaced femoral neck fractures treated with internal screw fixation. Since the failure rate of screw fixation for stable femoral neck fractures in elderly patients is not low, we believe that hemiarthroplasty is a reasonable treatment option in select patients. LEVEL OF EVIDENCE: Level III, Therapeutic study.

The Identification of Immune-Related Plasma Proteins Associated with Spontaneous Preterm Delivery and Intra-Amniotic Infection in Women with Premature Cervical Dilation or an Asymptomatic Short Cervix.

BACKGROUND: We aimed to investigate whether various immune-related plasma proteins, alone or in combination with conventional clinical risk factors, can predict spontaneous preterm delivery (SPTD) and intra-amniotic infection in women with premature cervical dilation or a short cervix (≤ 25 mm). METHODS: This retrospective study included 80 asymptomatic women with premature cervical dilation (n = 50) or a short cervix (n = 30), who underwent amniocentesis at 17-29 weeks. Amniotic fluid (AF) was cultured, and maternal plasma was assayed for interleukin (IL)-6, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and complements C3a and C5a, using enzyme-linked immunosorbent assay (ELISA) kits. The primary outcome measures were SPTD at < 32 weeks and positive AF cultures. RESULTS: The plasma levels of IL-6, C3a, and C5a, but not of MMP-9 and TIMP-1, were significantly higher in women with SPTD at < 32 weeks than in those who delivered at ≥ 32 weeks. The women who delivered at < 32 weeks had more advanced cervical dilatation, and higher rates of antibiotic and tocolytic administration and were less likely to be given vaginal progesterone than those who delivered at ≥ 32 weeks. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma IL-6 and C3a levels, and cervical dilatation (area under the curve [AUC], 0.901). The AUC for this model was significantly greater than that for any single variable included in the predictive model. In the univariate analysis, plasma IL-6 level was the only significant predictor of intra-amniotic infection. CONCLUSION: In women with premature cervical dilation or a short cervix, maternal plasma IL-6, C3a, and C5a levels could be useful non-invasive predictors of SPTD at < 32 weeks. A combination of these biomarkers and conventional clinical factors may clearly improve the predictability for SPTD, as compared with the biomarkers alone. An increased plasma level of IL-6 predicted intra-amniotic infection.

Hepatoprotective effects of an Acer tegmentosum Maxim extract through antioxidant activity and the regulation of autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Acer tegmentosum Maxim (AT), the East Asian stripe maple, is an herb used to treat liver disease and is approved as a functional food in Korea. AT protects against hepatic disorders, atopic dermatitis, and diabetes mellitus. AIM OF THE STUDY: We explored the mechanism of the hepatoprotective effects of AT extract in in vitro and in vivo levels. MATERIALS AND METHODS: AT extract from Acer tegmentosum Maxim was extracted by hot water. Hepatoprotective effects of AT extract were confirmed using carbon tetrachloride (CCl4)- or alcohol-induced mouse model, and H2O2- or alcohol-induced HepG2 (liver hepatocellular carcinoma cell line) cells by measuring GOT, GPT, TG, and MDA levels. Hematoxylin and eosin (H&E) staining was used to observe the pathological analysis. Cytotoxicity or protective effect of AT extract was confirmed using MTT assay in HepG2 cells. Antioxidant effect of AT extract was measured using DPPH or H2DCFDA assay. Mechanism study of antioxidant and autophagy was carried out using western blotting and immunofluorescence analysis. RESULTS: AT extract increased the viability of HepG2 cells treated with H2O2 and ethanol, and protected the liver against damage induced by CCl4 and alcohol. The AT extract increased the levels of nuclear respiratory factor 2 (Nrf2) and heme oxygenase-1 (HO-1). The level of microtubule-associated protein light chain 3 (LC3)-Ⅱ, beclin-1, autophagy-related genes (Atg) such as Atg3 and Atg12-5 as markers of autophagy activation was also increased. Moreover, the AT extract increased activation of mitogen-activated protein kinase (MAPK), which regulated autophagy and HO-1. CONCLUSION: Therefore, these results indicate that the AT extract has a hepatoprotective effect by increasing antioxidant activity and inducing autophagy.

Does short-term weekly teriparatide improve healing in unstable intertrochanteric fractures?

Slow recovery after hip fracture has been associated with negative consequences. Thus, there is medical need to improve healing and functional recovery after intertrochanteric fracture. The aim of this study was to measure whether short-term teriparatide would improve healing in intertrochanteric fractures after internal fixation as measured by (1) clinical scores, (2) radiographic fracture healing, and (3) complication rates. We retrospectively reviewed 96 patients (average age, 82 years) who underwent closed reduction and internal fixation with proximal femoral nail (PFN) for unstable intertrochanteric fractures between 2014 and 2016. Of the 96 patients, 56 patients were treated with a PFN alone (group 1). These patients were compared with 46 patients for whom the same device was used and a weekly subcutaneous injection of PTH 1-34 (teriparatide) was prescribed postoperatively (group 2). Questionnaire surveys or telephone interviews were conducted, and patients completed a self-report Harris hip score and visual analog scale scores. The radiological time to fracture healing was assessed as the primary end point. Postoperative complication rates were compared. Functional outcomes at 6 months after surgery were similar in both groups. There were no differences between groups in the proportion of patients achieving radiographic fracture healing. The frequency of patients reporting adverse events was 20% (10 of 50) in group 1 versus 17% (8 of 46) in group 2 ( p = 0.744). Short-term teriparatide did not improve radiographic signs of fracture healing of an intertrochanteric fracture and reduce the incidence of complications. The effect of teriparatide on fracture healing remains uncertain. Further multicenter prospective studies are needed to demonstrate objective long-term results of parathyroid hormone therapy in patient with hip fracture. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Per-oral cross-facial sural nerve graft for facial reanimation.

BACKGROUND: Cross-facial nerve graft is considered the treatment of choice for facial reanimation in patients with unilateral facial palsy caused by central facial nerve damage. In most cases, a traditional parotidectomy skin incision is used to locate the buccal and zygomatic branches of the facial nerve. METHODS: In this study, cross-facial nerve graft with the sural nerve was planned for three patients with facial palsy through an intraoral approach. RESULTS: An incision was made on the buccal cheek mucosa, and the dissection was performed to locate the buccal branch of the facial nerve. The parotid papillae and parotid duct were used as anatomic landmarks to locate the buccal branch. CONCLUSIONS: The intraoral approach is more advantageous than the conventional extraoral approach because of clear anatomic marker (parotid papilla), invisible postoperative scar, reduced tissue damage from dissection, and reduced operating time.

Plasma inflammatory and immune proteins as predictors of intra-amniotic infection and spontaneous preterm delivery in women with preterm labor: a retrospective study.

BACKGROUND: We investigated whether various inflammatory and immune proteins in plasma predict intra-amniotic infection and imminent preterm delivery in women with preterm labor and compared their predictive ability with that of amniotic fluid (AF) interleukin (IL)-6 and serum C-reactive protein (CRP). METHODS: This retrospective cohort study included 173 consecutive women with preterm labor who underwent amniocentesis for diagnosis of infection and/or inflammation in the AF. The AF was cultured, and assayed for IL-6. CRP levels and cervical length by transvaginal ultrasound were measured at the time of amniocentesis. The stored maternal plasma was assayed for IL-6, matrix metalloproteinase (MMP)-9, and complements C3a and C5a using ELISA kits. The primary and secondary outcome criteria were positive AF cultures and spontaneous preterm delivery (SPTD) within 48 h, respectively. Univariate, multivariate, and receiver operating characteristic analysis were used for the statistical analysis. RESULTS: In bivariate analyses, elevated plasma IL-6 level was significantly associated with intra-amniotic infection and imminent preterm delivery, whereas elevated plasma levels of MMP-9, C3a, and C5a were not associated with these two outcomes. On multivariate analyses, an elevated plasma IL-6 level was significantly associated with intra-amniotic infection and imminent preterm delivery after adjusting for confounders, including high serum CRP levels and short cervical length. In predicting intra-amniotic infection, the area under the curve (AUC) was significantly lower for plasma IL-6 than for AF IL-6 but was similar to that for serum CRP. Differences in the AUCs between plasma IL-6, AF IL-6, and serum CRP were not statistically significant in predicting imminent preterm delivery. CONCLUSIONS: Maternal plasma IL-6 independently predicts intra-amniotic infection in women with preterm labor; however, it has worse diagnostic performance than that of AF IL-6 and similar performance to that of serum CRP. To predict imminent preterm delivery, plasma IL-6 had an overall diagnostic performance similar to that of AF IL-6 and serum CRP. Plasma MMP-9, C3a, and C5a levels could not predict intra-amniotic infection or imminent preterm delivery.

An Enantioselective Total Synthesis of (+)-Duocarmycin SA.

An efficient, concise enantioselective total synthesis of the potent antitumor antibiotic (+)-duocarmycin SA is described. The invented route is based on a disconnection strategy that was devised to facilitate rapid and efficient synthesis of key core compounds to enable preclinical structure-activity relationship investigations. The key tricycle core was constructed with a highly enantioselective indole hydrogenation to set the stereocenter and a subsequent hitherto unexplored vicarious, nucleophilic-substitution/cyclization sequence to effectively forge a final indole ring. Additionally, the development of a stable sulfonamide protecting group capable of mild chemoselective cleavage greatly enhanced sequence yield and throughput. An understanding of key reaction parameters ensured a robust, reproducible sequence easily executable on decagram scales to this highly promising class of compounds.

Risk factors for failure in the newborn hearing screen test in very preterm twins.

BACKGROUND: We aimed to identify prenatal and postnatal risk factors associated with abnormal newborn hearing screen (NHS) results and subsequently confirmed sensorineural hearing loss (SNHL) in preterm twin neonates. METHODS: Electronic medical records of 159 twin neonates who were born alive after ≤32 weeks were retrospectively reviewed for hearing loss in both ears. Histopathologic examination of the placenta was performed and clinical data, including method of conception and factors specific to twins, were retrieved from a computerized perinatal database. The main outcome measure was failure to pass the NHS test. The generalized estimation equations model was used for twins. RESULTS: Thirty-two neonates (20.1%) had a "refer" result, and, on the confirmation test, permanent SNHL was identified in 4.4% (7/159) of all neonates. Neonates who had a "refer" result on the NHS test were more likely to be of lower birth weight, more likely to have been conceived with the use of in vitro fertilization (IVF), and more likely to have higher rates of intraventricular hemorrhage (IVH) and bronchopulmonary dysplasia. However, monochorionic placentation, death of the co-twin, or being born first was not associated with a "refer" result on the NHS test. Multivariable logistic regression revealed that conception after IVF and the presence of IVH were the only variables to be statistically significantly associated with "refer" on the NHS test. No parameters studied were found to be significantly different between the SNHL and no SNHL groups, probably because of the relatively small number of cases of SNHL. CONCLUSION: In preterm twin newborns, IVF and the presence of IVH were independently associated with an increased risk of abnormal NHS results, whereas the factors specific to twins were not associated with abnormal NHS results.

Brucella infection following total joint arthroplasty: A systematic review of the literature.

INTRODUCTION: The aim of this systematic review was to analyze the results of published treatment options in Brucella infection following total joint arthroplasty (TJA). METHODS: We performed a systematic review of the literature regarding outcomes of Brucella infection after TJA (hip and knee). We searched multiple databases for articles in the area published from 1950 to 2016. RESULTS: A total of 18 patients (12 male and 6 female; mean age 59 years) from 14 published studies were identified. The minimum follow-up time was 6 months (range, 6-120 months). Seven patients were treated with debridement or antibrucella treatment only. Eleven patients (61%) underwent removal of the prosthesis and were treated with one or two-stage exchange arthroplasty. The mean duration of antibiotic therapy was 5.8 months. There was no relapse of infection. CONCLUSIONS: In the absence of loosening of the components of the prosthesis, an attempt to treat Brucella infection medically might be a reasonable choice. One or two-stage exchange arthroplasty could provide successful results without relapse of infection when combined with appropriate antibiotherapy. LEVEL OF EVIDENCE: Level III, therapeutic study.

Lower preoperative Hounsfield unit values are associated with intra-operative fractures in cementless bipolar hemiarthroplasty.

The use of Hounsfield units (HU) from CT scanning to assess regional BMD has been described. Therefore, we evaluated whether HU could be used to identify osteoporosis of the proximal part of the femur. The results showed that HU assessment is associated with the presence of intra-operative fracture during arthroplasty. INTRODUCTION: The aim with this study was to determine the association of preoperative Hounsfield unit (HU) in hip computed tomography (CT) with intra-operative osteoporotic fracture during cementless hemiarthroplasty. METHODS: In this retrospective study, we reviewed all patients who underwent cementless bipolar hemiarthroplasty for femoral neck fractures between 2014 and 2016. Patients with intra-operative metaphyseal fractures (n = 25) during surgery were identified from a retrospectively collected patient database and matched with nonfracture controls (n = 75) on the basis of age and sex. The differences between patients with intra-operative fractures and without intra-operative fractures were compared regarding preoperative HU. Correlations of HU value of femur neck with BMD and T scores were determined. RESULTS: Analysis of HU values at the fracture level showed a significantly lower value in the fracture group than in the controls (1186 vs 1340, p = 0.005). The correlation between HU and BMD of femur neck was significant (r 2 = 0.347; p < 0.001). The correlation between HU of femur neck and BMD of spine was also significant (r 2 = 0.133; p < 0.001). CONCLUSIONS: HU assessment using preoperative CT scan is associated with the presence of intra-operative fracture during bipolar hemiarthroplasty. We believe that HU values of the proximal femur could be used to assess local bone quality.