bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term neurodevelopmental benefits of breastfeeding
Authors: Bar Sari , Milanaik Ruth , Adesman Andrew
Published: June 2016

Purpose of review

The American Academy of Pediatrics recommends exclusive breastfeeding for the first 6 months of an infant#$#apos;s life, with continuation of breastfeeding for at least a year or as mutually desired by mother and child. A robust body of research literature documenting the short-term medical, developmental, and emotional benefits of breastfeeding for infants and toddlers supports this position. This article reviews the neurodevelopmental benefits of breastfeeding as it relates to preschool and school-age children, with particular emphasis on cognitive development, attention-deficit/hyperactivity disorder, and autism spectrum disorder.

Recent findings

The majority of research studies examining breastfeeding and long-term neurodevelopmental outcomes suggest that children who breastfeed for longer than 6 months have better cognitive outcomes, lower risk of developing attention-deficit/hyperactivity disorder, and lower risk of being diagnosed with autism spectrum disorder.

Pediatricians play a critical role in educating and counseling families about infant nutrition and feeding. Along with the many positive short-term medical effects that breastfeeding confers, physicians should be aware of the growing body of research suggesting that there are also significant long-term neurodevelopmental benefits of breastfeeding.
SATB2 Expression Is Sensitive but Not Specific for Osteosarcomatous Components of Gynecologic Tract Carcinosarcomas: A Clinicopathologic Study of 60 Cases
Authors: Sangoi Ankur R. , Kshirsagar Malti , Horvai Andrew E. , Roma Andres A.
Published: June 2016

The novel marker special AT-rich sequence binding protein (SATB2) is highly sensitive for mesenchymal tumors with osteoblastic differentiation. However, SATB2 expression in gynecologic tract carcinosarcoma has not been previously explored. Given the potential prognostic and therapeutic implications of heterologous carcinosarcoma in the gynecologic tract, this study investigates the utility of SATB2 in identifying osteosarcomatous elements. A multi-institution database review identified consecutive cases of gynecologic tract carcinosarcoma including both heterologous and homologous types. Clinicopathologic parameters were recorded. Nuclear SATB2 immunoreactivity was scored from 1 representative whole-slide section from each case. Sixty gynecologic tract carcinosarcoma were identified (uterine corpus=47, ovary=11, fallopian tube=1, cervix=1) including 32 heterologous type (7 osteosarcoma, 3 mixed osteosarcoma/chondrosarcoma, 6 chondrosarcoma, 12 rhabdomyosarcoma, 4 mixed chondrosarcoma/rhabdomyosarcoma) and 28 homologous type. Patient ages ranged from 41 to 90 yr (average 67.9 yr). Mostly diffuse strong SATB2 positivity was present in 10/10 (100%) cases containing osteosarcoma. In these cases, SATB2 positivity was seen in malignant cells intimately associated with osteoid or bone [3/10 (30%) of these cases additionally showed patchy weak/moderate SATB2 staining in areas of nonosteogenic sarcoma elsewhere in the same tumor]. SATB2 positivity was present in 30/50 (60%) cases lacking osteosarcoma, predominantly as patchy moderate staining within undifferentiated sarcoma. No cases showed SATB2 positivity in chondrosarcoma or rhabdomyosarcoma components. SATB2 is a highly sensitive marker for osteosarcomatous differentiation in gynecologic tract carcinosarcoma, and is also highly specific when used to differentiate osteosarcoma from chondrosarcoma and rhabdomyosarcoma elements in these tumors. However, a positive SATB2 result may lack specificity for differentiating osteosarcoma from an undifferentiated sarcoma component.
Hypoxic-Ischemic Encephalopathy With Clinical and Imaging Abnormalities Limited to Occipital Lobe
Authors: Parmar Hemant A. , Trobe Jonathan D.
Published: June 2016

Background:

The vulnerable brain areas in hypoxic-ischemic encephalopathy (HIE) following systemic hypotension are typically the neocortex, deep cerebral gray nuclei, hippocampus, cerebellum, and the parieto-occipital arterial border zone region. The visual cortex is not commonly recognized as a target in this setting.

Methods:

Single-institution review from 2007 to 2015 of patients who suffered cortical visual loss as an isolated clinical manifestation following systemic hypotension and whose brain imaging showed abnormalities limited to the occipital lobe.

Results:

Nine patients met inclusion criteria. Visual loss at outset ranged from hand movements to 20/20, but all patients had homonymous field loss at best. In 1 patient, imaging was initially normal but 4 months later showed encephalomalacia. In 2 patients, imaging was initially subtle enough to be recognized as abnormal only when radiologists were advised that cortical visual loss was present.

Conclusions:

The occipital lobe may be an isolated target in HIE with cortical visual loss as the only clinical manifestation. Imaging performed in the acute period may appear normal or disclose abnormalities subtle enough to be overlooked. Radiologists informed of the clinical manifestations may be more attune to these abnormalities, which will become more apparent months later when occipital volume loss develops.
To what extent are the terminal stages of sepsis, septic shock, SIRS, and multiple organ dysfunction syndrome actually driven by a prion/amyloid form of fibrin?
Authors: Kell Douglas B. , Pretorius Etheresia
Published: June 2016

A well-established development of increasing disease severity leads from sepsis through septic shock, SIRS, multiple organ dysfunction syndrome and cellular and organismal death. We argue that a chief culprit is the LPS-induced anomalous coagulation of fibrinogen to produce a form of fibrin that is at once inflammatory, resistant to fibrinolysis, and underpins the disseminated intravascular coagulation commonly observed in sepsis. In particular, we argue that the form of fibrin produced is anomalous because much of its normal α-helical content is transformed to β-sheets, as occurs in established amyloidogenic and prion diseases. We hypothesise that these processes play a major role in the passage along the above pathways to organismal death, and that inhibiting them would be of great therapeutic value, a claim for which there is emerging evidence.
Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease
Authors: de Lange Katrina M. , Moutsianas Loukas , Lee James C. , Lamb Christopher A. , Luo Yang , Kennedy Nicholas A. , Jostins Luke , Rice Daniel L. , Gutierrez-Achury Javier , Ji Sun-Gou , Heap Graham , Nimmo Elaine R. , Edwards Cathryn , Henderson Paul , Mowat Craig , Sanderson Jeremy , Satsangi Jack , Simmons Alison , Wilson David C. , Tremelling Mark , Hart Ailsa , Mathew Christopher G. , Newman William G. , Parkes Miles , Lees Charlie W. , Uhlig Holm , Hawkey Chris , Prescott Natalie J. , Ahmad Tariq , Mansfield John C. , Anderson Carl A. , Barrett Jeffrey C.
Published: June 2016

Genetic association studies have identified 210 risk loci for inflammatory bowel disease1–7, which have revealed fundamental aspects of the molecular biology of the disease, including the roles of autophagy and Th17 cell signaling and development. We performed a genome-wide association study of 25,305 individuals, and meta-analyzed with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 26 new genome-wide significant loci, three of which contain integrin genes that encode molecules in pathways identified as important therapeutic targets in inflammatory bowel disease. The associated variants are also correlated with expression changes in response to immune stimulus at two of these genes (ITGA4, ITGB8) and at two previously implicated integrin loci (ITGAL, ICAM1). In all four cases, the stimulus-dependent expression increasing allele also increases disease risk. We applied summary statistic fine-mapping and identified likely causal missense variants in the primary immune deficiency genePLCG2and the negative regulator of inflammation,SLAMF8. Our results demonstrate that new common variant associations continue to identify genes and pathways of relevance to therapeutic target identification and prioritization.
Combined hybridization capture and shotgun sequencing for ancient DNA analysis of extinct wild and domestic dromedary camel
Authors: Mohandesan Elmira , Speller Camilla F. , Peters Joris , Uerpmann Hans‐Peter , Uerpmann Margarethe , De Cupere Bea , Hofreiter Michael , Burger Pamela A.
Published: June 2016

The performance of hybridization capture combined with next‐generation sequencing (NGS) has seen limited investigation with samples from hot and arid regions until now. We applied hybridization capture and shotgun sequencing to recover DNA sequences from bone specimens of ancient‐domestic dromedary (Camelus dromedarius) and its extinct ancestor, the wild dromedary from Jordan, Syria, Turkey and the Arabian Peninsula, respectively. Our results show that hybridization capture increased the percentage of mitochondrial DNA (mtDNA) recovery by an average 187‐fold and in some cases yielded virtually complete mitochondrial (mt) genomes at multifold coverage in a single capture experiment. Furthermore, we tested the effect of hybridization temperature and time by using a touchdown approach on a limited number of samples. We observed no significant difference in the number of unique dromedary mtDNA reads retrieved with the standard capture compared to the touchdown method. In total, we obtained 14 partial mitochondrial genomes from ancient‐domestic dromedaries with 17–95% length coverage and 1.27–47.1‐fold read depths for the covered regions. Using whole‐genome shotgun sequencing, we successfully recovered endogenous dromedary nuclear DNA (nuDNA) from domestic and wild dromedary specimens with 1–1.06‐fold read depths for covered regions. Our results highlight that despite recent methodological advances, obtaining ancient DNA (aDNA) from specimens recovered from hot, arid environments is still problematic. Hybridization protocols require specific optimization, and samples at the limit of DNA preservation need multiple replications of DNA extraction and hybridization capture as has been shown previously for Middle Pleistocene specimens.
Juxtapapillary choroid is thinner in normal‐tension glaucoma than in healthy eyes
Authors: Lee Kyoung Min , Lee Eun Ji , Kim Tae‐Woo
Published: June 2016

Purpose

To measure the juxtapapillary choroidal thickness in eyes with normal‐tension glaucoma (NTG) and to compare it with healthy eyes.

Methods

Twelve radial B‐scan images of the optic nerve head (ONH) were obtained from 96 patients with NTG and 48 healthy subjects matched by age using swept‐source (SS) optical coherence tomography (OCT). The juxtapapillary choroidal thickness was defined as the average choroidal thickness within 500 μm from the border tissue of Elschnig. Choroidal thinning in patients with NTG was assessed by calculating the relative choroidal thickness, defined as the ratio of the measured juxtapapillary choroidal thickness in each meridian to the corresponding value in age‐matched healthy controls. Retinal nerve fibre layer (RNFL) damage as reflected by circumpapillary RNFL thickness (measured using spectral‐domain OCT) was also assessed.

Results

The juxtapapillary choroid was significantly thinner in NTG eyes than in healthy control eyes in the inferotemporal and superotemporal sectors. The relative choroidal thinning was topographically associated with the hemispheric location of dominant RNFL damage. The average juxtapapillary choroidal thickness was not associated with either the global RNFL thickness or the visual field mean deviation. Age and untreated intraocular pressure were significantly associated with the juxtapapillary choroidal thickness in NTG eyes in both univariate and multivariate analyses (all p < 0.05).

Conclusions

Decreased microvascular circulation in the ONH as a result of juxtapapillary choroidal thinning could be an important part of the pathogenesis of optic nerve damage in NTG.
Effect of femtosecond laser‐assisted lens surgery on posterior capsule opacification in the human capsular bag in vitro
Authors: Wertheimer Christian , Kreutzer Thomas C. , Dirisamer Martin , Eibl‐Lindner Kirsten , Kook Daniel , Priglinger Siegfried , Mayer Wolfgang J.
Published: June 2016

Purpose

To compare posterior capsule opacification (PCO) by observing lens epithelial cell growth in the human capsular bag in vitro between conventional lens surgery using phacoemulsification (Phaco) technique and femtosecond laser‐assisted lens surgery (FLACS).

Methods

For the in vitro human capsular bag model, 18 cadaver eyes from nine human donors underwent three types of lens surgery. Three groups consisting of six capsular bags were established, that is FLACS, Phaco and extracapsular lens extraction (ECCE). The capsular bag was transferred into equal cell culture conditions after using one of the defined surgical approaches. Cellular growth of lens epithelial cells was observed and photo‐documented. The time until full cell‐coverage of the capsular bag was measured.

Results

The human capsular bag model can be successfully prepared using FLACS. There was no statistically significant difference in time until cell‐coverage of the human donor capsular bag in vitro in all three surgical settings (ECCE versus Phaco p = 0.6; ECCE versus FLACS p = 1.0; Phaco versus FLACS p = 1.0).

Conclusions

In our in vitro human capsular bag model, we could not observe a statistically significant difference in PCO formation using different surgical approaches of lens extraction. Therefore, PCO formation might not be attributed to the type of surgery. Furthermore, this study shows that FLACS can be used for the human capsular bag model preparation and validates the human capsular bag model for future research.
Rizatriptan overuse promotes hyperalgesia induced by dural inflammatory stimulation in rats by modulation of the serotonin system
Authors: Su Min , Ran Ye , Han Xun , Liu Yufei , Zhang Xu , Tan Qingche , Li Ruisheng , Yu Shengyuan
Published: June 2016

Clinical and preclinical studies have implicated serotonin (5‐HT) and the 5‐HT2A receptor (5‐HT2AR) in the pathogenesis of medication‐overuse headache (MOH). However, with no appropriate animal model to study this phenomenon it is difficult to differentiate the effects of chronic exposure to analgesics from the consequences of frequent headache attacks during the development of MOH. Therefore, this study used a novel animal model of MOH established by a combination of the overuse of rizatriptan (RIZ) and stimulation with dural inflammatory soup (IS) to investigate whether 5‐HT and 5‐HT2AR are involved in central plasticity and hyperalgesia. Similar to an IS infusion, IS‐RIZ treatment induced nociception‐related behaviours in Sprague–Dawley rats and increased Fos expression in the cortex and trigeminal pathway, whereas the RIZ injection alone did not. In addition, overuse of RIZ, administration of an IS stimulus, and a combination of these treatments, decreased the periorbital withdrawal threshold, with IS‐RIZ treatment having the most significant effects. Both chronic RIZ exposure and recurring nociception decreased 5‐HT expression, whereas IS‐RIZ treatment led to decreased expression of 5‐HT and upregulation of 5‐HT2AR, which was positively correlated with Fos activation. These findings suggest that overuse of RIZ does not directly induce pain via the activation of nociceptive pathways but may increase hyperalgesia by influencing the pain modulation system. Furthermore, decreased 5‐HT levels and upregulation of 5‐HT2AR may play important roles in this system. Taken together, these findings indicate that medication overuse and frequent headache attacks can promote the neural plasticity associated with MOH.
Atrophy of the pedunculopontine nucleus region in patients with sleep‐predominant seizures: A voxel‐based morphometry study
Authors: Cho Kyoo Ho , Cho Yang‐Je , Lee Byung In , Heo Kyoung
Published: June 2016

Non–rapid eye movement (NREM) sleep increases interictal epileptiform discharges and frequency of seizures, whereas REM sleep suppresses them. The pedunculopontine nucleus (PPN), one of the REM sleep–modulating structures, is postulated to have a potent antiepileptogenic role. We asked if patients with sleep‐predominant seizures (SPS) show volume changes in the region of the PPN compared to those with seizures occurring during awake state only (nSPS). The volume of the PPN region was assessed in patients with SPS, those with nSPS, and healthy volunteers, through voxel‐based morphometry and automated, nonbiased region of interest (ROI) analysis of T1 magnetic resonance (MR) images. The volume of PPN region was statistically smaller in patients with SPS (n = 33) than in those with nSPS (n = 40) and healthy controls (n = 30) after controlling for covariates. These results suggest that a structural change in the PPN may be associated with sleep‐predominant timing of seizure occurrence. Our findings might help understand the intervening pathomechanism that lies between the human sleep–wake cycle and epilepsy.
Risk stratification of decompensated cirrhosis patients by Chronic Liver Failure Consortium scores: Classification and regression tree analysis
Authors: Shi Yu , Shu Zheyue , Sun Wenjie , Yang Qiao , Yu Ye , Yang Gang , Wu Wei , Chen Si , Huang Wei , Wang Tingting , Yan Huadong
Published: June 2016

Aim

Decompensated cirrhosis patients have greatly variable prognosis. The aim of the study was to carry out a risk stratification for those patients by Chronic Liver Failure (CLIF) Consortium scores.

Methods

The performance of CLIF Consortium acute‐on‐chronic liver failure scores (CLIF‐C ACLFs) and CLIF Consortium Acute Decompensation scores (CLIF‐C ADs) were validated in 209 patients with ACLF and 1245 patients without ACLF at admission from the Ningbo Cohort. A classification and regression tree (CRT) analysis by CLIF‐C ACLFs/CLIF‐C ADs was carried out to stratify death risk among patients.

Results

The CLIF‐C ACLFs and CLIF‐C ADs showed higher predictive accuracy than Model for End‐stage Liver Disease (MELD) scores, MELD plus serum sodium (MELD‐Na) scores, and Child–Turcotte–Pugh classification (CP) at main time points (28, 90, 180, and 365 days), determined by area under the receiver–operating characteristic curve and concordance index in ACLF and no‐ACLF patients at admission. The CRT analysis categorized ACLF patients into two groups (advanced and early ACLF), and no‐ACLF patients into three groups (high‐, medium‐, and low‐risk AD) according to risk of death. However, early ACLF and high‐risk AD patients had comparable mortality at the main time points. The CRT model had a higher area under the receiver–operating characteristic curve than MELDs, MELD‐Nas, and CPs in predicting prognosis in all patients.

Conclusions

The CLIF‐C ACLF and CLIF‐C AD are better prognostic scores than MELD, MELD‐Na, and CP in predicting mortality of ACLF and no‐ACLF patients. A combined use of CLIF– Sequential Organ Failure Assessment, CLIF‐C ACLFs, and CLIF‐C ADs could identify cirrhosis patients at high death risk and assist clinical decisions for management.
Effect of standard tuberculosis treatment on naive, memory and regulatory T‐cell homeostasis in tuberculosis–diabetes co‐morbidity
Authors: Kumar Nathella P. , Moideen Kadar , Viswanathan Vijay , Kornfeld Hardy , Babu Subash
Published: June 2016

Perturbations in CD4+ and CD8+ T‐cell phenotype and function are hallmarks of tuberculosis–diabetes co‐morbidity. However, their contribution to the pathogenesis of this co‐morbidity and the effect of anti‐tuberculosis treatment on the phenotype of the T‐cell subsets is poorly understood. In this study, we examined the frequency of different T‐cell subsets in individuals with pulmonary tuberculosis (PTB) with diabetes mellitus (DM) or without coincident diabetes mellitus (NDM) before, during and after completion of anti‐tuberculosis chemotherapy. PTB‐DM is characterized by heightened frequencies of central memory CD4+ and CD8+ T cells and diminished frequencies of naive, effector memory and/or effector CD4+ and CD8+ T cells at baseline and after 2 months of treatment but not following treatment completion in comparison with PTB‐NDM. Central memory CD4+ and CD8+ T‐cell frequencies exhibited a positive correlation with fasting blood glucose and glycated haemoglobin A1c levels, whereas the frequencies of naive and effector memory or effector CD4+ and CD8+ T cells exhibited a negative correlation. However, the frequencies of CD4+ and CD8+ T‐cell subsets in individuals with PTB exhibited no significant relationship with bacterial burdens. Finally, although minor alterations in the T‐cell subset compartment were observed at 2 months of treatment, significantly decreased frequencies of central memory and significantly enhanced frequencies of naive CD4+ and CD8+ T cells were observed at the completion of treatment. Our data reveal a profound effect of coexistent diabetes on the altered frequencies of central memory, effector memory and naive T cells and its normalization following therapy.
Impact of FIB‐4 index on hepatocellular carcinoma incidence during nucleos(t)ide analogue therapy in patients with chronic hepatitis B: An analysis using time‐dependent receiver operating characteristic
Authors: Tada Toshifumi , Kumada Takashi , Toyoda Hidenori , Tsuji Kunihiko , Hiraoka Atsushi , Tanaka Junko
Published: June 2016

Background and Aim

Nucleos(t)ide analogue (NA) therapy has been reported to reduce the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). However, even during NA therapy, development of HCC has been observed in patients with CHB. Therefore, we clarified the predictive power of clinical factors for HCC incidence using receiver operating characteristic (ROC) analysis that takes time dependence into account.

Methods

A total of 539 patients with CHB treated with NAs were enrolled. Univariate, multivariate, and time‐dependent ROC curves for clinical factors associated with the development of HCC were analyzed.

Results

Eighty‐one patients developed HCC during the follow‐up period (median duration, 5.9 years). α‐fetoprotein (AFP) and FIB‐4 index at 24 weeks from the initiation of treatment and sex were significantly associated with HCC incidence according to the log‐rank test. Cox proportional hazards models including the covariates of sex, hepatitis B genotype, basal core promoter mutations, AFP at 24 weeks, and FIB‐4 index at 24 weeks showed that FIB‐4 index >2.65 (HR, 5.03; 95% CI, 3.06–8.26; P < 0.001) and male sex were independently associated with HCC incidence. In addition, time‐dependent ROC analysis showed that compared with AFP at 24 weeks, FIB‐4 index at 24 weeks had higher predictive power for HCC incidence throughout the follow‐up period.

Conclusions

Elevated FIB‐4 index at 24 weeks in patients with CHB receiving NA therapy is a risk factor for developing HCC. The FIB‐4 index is an excellent predictor of HCC development.
Asthma and sleep disturbance in adolescents and young adults: A cohort study
Authors: Garden Mark , O'Callaghan Michael , Suresh Sadasivam , Mamum Abdullah A , Najman Jake M
Published: June 2016

Aims

A longitudinal birth cohort provides an opportunity to study the impact of childhood conditions persisting into adulthood. This study examines the cross‐sectional association of asthma with sleep quality and snoring in the adolescent and young adult population and the extent to which asthma, sleep quality and snoring at 14 years independently predict themselves or each other at 21 years.

Methods

Data from a 21‐year follow‐up of mothers and their children recruited into the Mater–University of Queensland Study of Pregnancy (n = 7223). Complete asthma and sleep information (questionnaire data) was available for 5015 participants at 14 years and 3527 at 21 years, with 3237 participants at both 14 and 21 years.

Results

Poor sleep quality and snoring were independently associated with asthma at 14 years and 21 years, with stronger associations evident in women. At 21 years, associations were mediated by asthma symptom severity. Asthma, sleep quality and snoring at 14 years each strongly and independently predicted themselves at 21 years. Asthma at 14 years predicted snoring at 21 years, while poor sleep quality and snoring in women predicted asthma at 21 years, the latter partially mediated by body mass index.

Conclusions

The relationship between asthma, sleep quality and snoring varied by gender. Sleep quality and snoring should be considered in the assessment and holistic management of asthma. The predictive relationship seen between 14 and 21 years provides an opportunity to address these issues at a younger age.
The proportion of local allergic rhinitis to Dermatophagoides pteronyssinus in children
Authors: Buntarickpornpan Pichittra , Veskitkul Jittima , Pacharn Punchama , Visitsunthorn Nualanong , Vichyanond Pakit , Tantilipikorn Pongsakorn , Jirapongsananuruk Orathai
Published: June 2016

Background

Local allergic rhinitis (LAR) is diagnosed by the positive response to nasal allergen provocation test (NAPT) to aeroallergen and/or local synthesis of specific IgE (sIgE). This entity is found in half of the adults with non‐allergic rhinitis (NAR). In children, very few data of the prevalence and characteristics of LAR were reported.

Methods

Children 8–18 years with NAR were recruited. A NAPT with Dermatophagoides pteronyssinus extract (NAPT‐Dp) at 200, 600, and 2000 AU/ml, respectively, at 15‐min interval was performed. The immediate response was assessed using the clinical symptom score, peak nasal inspiratory flow (PNIF), and acoustic rhinometry (ARM). The nasal tryptase and sIgE‐Dp were measured at baseline and 15 min and 1 h after a positive NAPT‐Dp. Two allergic rhinitis (AR) patients were used as positive controls.

Results

Fifty‐four NAR children (61.1% boys) with the mean ± SD age of 11.1 ± 2.1 years were enrolled. The median duration of disease was 6.3 years. The most frequent comorbidity was asthma (38.9%). Eighty‐seven percent of patients had mild persistent severity. NAPT‐Dp was positive in 2/54 (3.7%) of NAR children who had increased symptom score and decreased minimal cross‐sectional area (MCA) on ARM as well as PNIF. However, there was no change in the nasal tryptase and sIgE‐Dp. The control AR patients had positive NAPT‐Dp and increased nasal tryptase at 15 min without the change of sIgE‐Dp.

Conclusion

LAR is an uncommon condition in children. Further investigation in a large population of children with NAR is needed.
The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations
Authors: Meeth Katrina , Wang Jake Xiao , Micevic Goran , Damsky William , Bosenberg Marcus W.
Published: June 2016

The remarkable success of immune therapies emphasizes the need for immune‐competent cancer models. Elegant genetically engineered mouse models of a variety of cancers have been established, but their effective use is limited by cost and difficulties in rapidly generating experimental data. Some mouse cancer cell lines are transplantable to immunocompetent host mice and have been utilized extensively to study cancer immunology. Here, we describe the Yale University Mouse Melanoma (YUMM) lines, a comprehensive system of mouse melanoma cell lines that are syngeneic to C57BL/6, have well‐defined human‐relevant driver mutations, and are genomically stable. This will be a useful tool for the study of tumor immunology and genotype‐specific cancer biology.
Hemophagocytic lymphohistiocytosis: Pathogenesis, diagnosis, and management
Authors: Morimoto Akira , Nakazawa Yozo , Ishii Eiichi
Published: June 2016

Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening hyperinflammatory syndrome that is classified into primary and secondary HLH. Primary HLH consists of monogenic disorders that mainly affect the perforin‐mediated cytotoxicity of cytotoxic T lymphocytes and natural killer cells. Secondary HLH occurs as a complication in various settings such as infection, malignancy, autoimmune disease, and post‐allogeneic hematopoietic stem cell transplantation. Both primary and secondary HLH are characterized by uncontrolled hypercytokinemia that results in myelosuppression and vascular endothelium damage. More than 10% of patients with HLH die within 2 months of diagnosis due to bleeding in the visceral organs, opportunistic infection due to neutropenia, or multiple organ failure. The most obvious presentations of HLH are persistent fever refractory to antimicrobial agents and hyperferritinemia due to hypersecretion of various cytokines. The first rule is not to overlook signs of hypercytokinemia and to settle the hyperactivated immunological state as soon as possible. In addition, to improve outcome, it is essential to identify the disorders underlying HLH and provide disorder‐appropriate treatment.
Childhood sexual abuse and supportive factors
Authors: Baytunca Muharrem Burak , Ata Emsal , Ozbaran Burcu , Kaya Ahsen , Kose Sezen , Aktas Ekin Ozgur , Aydın Rezzan , Guney Selcen , Yuncu Zeki , Erermis Serpil , Bildik Tezan , Aydin Cahide
Published: June 2016

Background

Childhood sexual abuse (CSA) can be a devastating life experience and is associated with a higher incidence of mental disorders and suicide attempts. The aim of this study was therefore to identify predictors of mental disorder and suicide attempt in children and adolescents with a history of CSA.

Methods

A total of 181 Turkish children and adolescents with a history of CSA were evaluated for age, gender, suicide attempts, family relationships and educational background. Abuse involving the insertion of an organ or foreign object into the individual's body was designated as “qualified sexual abuse” (QSA); other forms of sexual abuse were designated “basic sexual abuse” (BSA).

Results

Suicide attempts were significantly higher in adolescent girls in the QSA subgroup; age, gender, family integrity, and school attendance were not associated with risk of mental disorders in this group. Among BSA patients, family integrity was significantly associated with suicide attempts. Suicide attempts were approximately 10‐fold higher (OR, 10.154; 95% CI: 2.020–51.051; P = 0.005) in children from broken families. Family integrity and school attendance were also noted as weak protective factors against mental disorders in BSA patients. The incidence of mental disorders was 3.5‐fold higher in children who had not been attending school (OR, 3.564; 95% CI: 1.379–9.211; P = 0.009).

Conclusion

Family integrity and school attendance were weakly related with psychopathology (e.g. mental disorders or suicide attempts) in BSA survivors but not in QSA survivors. Female gender and puberty also increased the likelihood of suicide attempt in QSA survivors.
Identification of a Fluorescent Protein from Rhacostoma Atlantica
Authors: Tota Michael R. , Allen Jeanna M. , Karolin Jan O. , Geddes Chris D. , Ward William W.
Published: June 2016

We have cloned a novel fluorescent protein from the jellyfish Rhacostoma atlantica. The closest known related fluorescent protein is the Phialidium yellow fluorescent protein, with only a 55% amino acid sequence identity. A somewhat unusual alanine–tyrosine–glycine amino acid sequence forms the presumed chromophore of the novel protein. The protein has an absorption peak at 466 nm and a fluorescence emission peak at 498 nm. The fluorescence quantum yield was measured to be 0.77 and the extinction coefficient is 58 200 M−1 cm−1. Several mutations were identified that shift the absorption peak to about 494 nm and the emission peak to between 512 and 514 nm.
Multiphase dolomitization of deeply buried Cambrian petroleum reservoirs, Tarim Basin, north‐west China
Authors: Jiang Lei , Cai Chunfang , Worden Richard H. , Crowley Stephen F. , Jia Lianqi , Zhang Ke , Duncan Ian J.
Published: June 2016

Cambrian dolostone reservoirs in the Tarim Basin, China, have significant potential for future discoveries of petroleum, although exploration and production planning is hampered by limited understanding of the occurrence and distribution of dolomite in such ancient rocks buried to nearly 8 km. The study herein accessed new drill core samples which provide an opportunity to understand the dolomitization process in deep basins and its impact on Cambrian carbonate reservoirs. This study documents the origin of the dolostone reservoirs using a combination of petrology, fluid‐inclusion microthermometry, and stable and radiogenic‐isotopes of outcrop and core samples. An initial microbial dolomitization event occurred in restricted lagoon environments and is characterized by depleted δ13C values. Dolomicrite from lagoonal and sabkha facies, some fabric‐retentive dolomite and fabric‐obliterative dolomite in the peloidal shoal and reef facies show the highest δ18O values. These dolomites represent relatively early reflux dolomitization. The local occurrence of K‐feldspar in dolomicrite indicates that some radiogenic strontium was contributed via terrigenous input. Most fabric‐retentive dolomite may have precipitated from seawater at slightly elevated temperatures, suggested by petrological and isotopic data. Most fabric‐obliterative dolomite, and medium to coarse dolomite cement, formed between 90°C and 130°C from marine evaporitic brine. Saddle dolomite formed by hydrothermal dolomitization at temperatures up to 170°C, and involved the mixing of connate brines with Sr‐ enriched hydrothermal fluids. Intercrystalline, moldic, and breccia porosities are due to the early stages of dolomitization. Macroscopic, intergranular, vuggy, fracture and dissolution porosity are due to burial‐related dissolution and regional hydrothermal events. This work has shown that old (for example, Cambrian or even Precambrian) sucrosic dolomite with associated anhydrite, buried to as much as 8000 m, can still have a high potential for hosting substantial hydrocarbon resources and should be globally targeted for future exploration.
Anticipated Stigma and Defensive Individualism During Postincarceration Job Searching*
Authors: Ray Bradley , Grommon Eric , Rydberg Jason
Published: June 2016

Obtaining employment is one of the most difficult challenges for individuals released from prison. This research explores the strategies recently released male parolees employ in attempting to find work, with specific attention to the role of anticipated stigma from their ex‐convict status. Through the use of in‐depth longitudinal interviews, this research contributes to our understanding of returning prisoner's experiences in job searching. We find that although a majority of the sample anticipated stigma as a barrier to employment, those who did expressed an extreme self‐reliance consistent with defensive individualism. This reluctance to draw on social networks may ultimately be counter‐productive to the search for employment.
Waveguide metatronics: Lumped circuitry based on structural dispersion
Authors: Li Yue , Liberal Iñigo , Della Giovampaola Cristian , Engheta Nader
Published: June 2016

A microwave test bed for metatronic “lumped” circuitry is introduced by exploiting structural dispersion in waveguides.
Interfacial gauge methods for incompressible fluid dynamics
Authors: Saye Robert
Published: June 2016

A new class of numerical algorithms facilitates accurate computational modeling of intricate fluid interface phenomena.
DUF3380 Domain from a Salmonella Phage Endolysin Shows Potent
N
-Acetylmuramidase Activity
Authors: Rodríguez-Rubio Lorena , Gerstmans Hans , Thorpe Simon , Mesnage Stéphane , Lavigne Rob , Briers Yves
Published: June 2016

Bacteriophage-encoded endolysins are highly diverse enzymes that cleave the bacterial peptidoglycan layer. Current research focuses on their potential applications in medicine, in food conservation, and as biotechnological tools. Despite the wealth of applications relying on the use of endolysin, little is known about the enzymatic properties of these enzymes, especially in the case of endolysins of bacteriophages infecting Gram-negative species. Automated genome annotations therefore remain to be confirmed. Here, we report the biochemical analysis and cleavage site determination of a novel
Salmonella
bacteriophage endolysin, Gp110, which comprises an uncharacterized
d
omain of
u
nknown
f
unction (DUF3380; pfam11860) in its C terminus and shows a higher specific activity (34,240 U/μM) than that of 14 previously characterized endolysins active against peptidoglycan from Gram-negative bacteria (corresponding to 1.7- to 364-fold higher activity). Gp110 is a modular endolysin with an optimal pH of enzymatic activity of pH 8 and elevated thermal resistance. Reverse-phase high-performance liquid chromatography (RP-HPLC) analysis coupled to mass spectrometry showed that DUF3380 has
N
-acetylmuramidase (lysozyme) activity cleaving the β-(1,4) glycosidic bond between
N
-acetylmuramic acid and
N
-acetylglucosamine residues. Gp110 is active against directly cross-linked peptidoglycans with various peptide stem compositions, making it an attractive enzyme for developing novel antimicrobial agents.

IMPORTANCE
We report the functional and biochemical characterization of the
Salmonella
phage endolysin Gp110. This endolysin has a modular structure with an enzymatically active domain and a cell wall binding domain. The enzymatic activity of this endolysin exceeds that of all other endolysins previously characterized using the same methods. A domain of unknown function (DUF3380) is responsible for this high enzymatic activity. We report that DUF3380 has
N
-acetylmuramidase activity against directly cross-linked peptidoglycans with various peptide stem compositions. This experimentally verified activity allows better classification and understanding of the enzymatic activities of endolysins, which mostly are inferred by sequence similarities. Three-dimensional structure predictions for Gp110 suggest a fold that is completely different from that of known structures of enzymes with the same peptidoglycan cleavage specificity, making this endolysin quite unique. All of these features, combined with increased thermal resistance, make Gp110 an attractive candidate for engineering novel endolysin-based antibacterials.
Regulation of Pyrroloquinoline Quinone-Dependent Glucose Dehydrogenase Activity in the Model Rhizosphere-Dwelling Bacterium Pseudomonas putida KT2440
Authors: An Ran , Moe Luke A.
Published: June 2016

Soil-dwelling microbes solubilize mineral phosphates by secreting gluconic acid, which is produced from glucose by a periplasmic glucose dehydrogenase (GDH) that requires pyrroloquinoline quinone (PQQ) as a redox coenzyme. While GDH-dependent phosphate solubilization has been observed in numerous bacteria, little is known concerning the mechanism by which this process is regulated. Here we use the model rhizosphere-dwelling bacterium
Pseudomonas putida
KT2440 to explore GDH activity and PQQ synthesis, as well as gene expression of the GDH-encoding gene (
gcd
) and PQQ biosynthesis genes (
pqq
operon) while under different growth conditions. We also use reverse transcription-PCR to identify transcripts from the
pqq
operon to more accurately map the operon structure. GDH specific activity and PQQ levels vary according to growth condition, with the highest levels of both occurring when glucose is used as the sole carbon source and under conditions of low soluble phosphate. Under these conditions, however, PQQ levels limit
in vitro
phosphate solubilization. GDH specific activity data correlate well with
gcd
gene expression data, and the levels of expression of the
pqqF
and
pqqB
genes mirror the levels of PQQ synthesized, suggesting that one or both of these genes may serve to modulate PQQ levels according to the growth conditions. The
pqq
gene cluster (
pqqFABCDEG
) encodes at least two independent transcripts, and expression of the
pqqF
gene appears to be under the control of an independent promoter and terminator.

IMPORTANCE
Plant growth promotion can be enhanced by soil- and rhizosphere-dwelling bacteria by a number of different methods. One method is by promoting nutrient acquisition from soil. Phosphorus is an essential nutrient that plants obtain through soil, but in many cases it is locked up in forms that are not available for plant uptake. Bacteria such as the model bacterium
Pseudomonas putida
KT2440 can solubilize insoluble soil phosphates by secreting gluconic acid. This chemical is produced from glucose by the activity of the bacterial enzyme glucose dehydrogenase, which requires a coenzyme called PQQ. Here we have studied how the glucose dehydrogenase enzyme and the PQQ coenzyme are regulated according to differences in bacterial growth conditions. We determined that glucose dehydrogenase activity and PQQ production are optimal under conditions when the bacterium is grown with glucose as the sole carbon source and under conditions of low soluble phosphate.
Metabolism of
myo
-Inositol by Legionella pneumophila Promotes Infection of Amoebae and Macrophages
Authors: Manske Christian , Schell Ursula , Hilbi Hubert
Published: June 2016

Legionella pneumophila
is a natural parasite of environmental amoebae and the causative agent of a severe pneumonia termed Legionnaires' disease. The facultative intracellular pathogen employs a bipartite metabolism, where the amino acid serine serves as the major energy supply, while glycerol and glucose are mainly utilized for anabolic processes. The
L. pneumophila
genome harbors the cluster
lpg1653
to
lpg1649
putatively involved in the metabolism of the abundant carbohydrate
myo
-inositol (here termed inositol). To assess inositol metabolism by
L. pneumophila
, we constructed defined mutant strains lacking
lpg1653
or
lpg1652
, which are predicted to encode the inositol transporter IolT or the inositol-2-dehydrogenase IolG, respectively. The mutant strains were not impaired for growth in complex or defined minimal media, and inositol did not promote extracellular growth. However, upon coinfection of
Acanthamoeba castellanii
, the mutants were outcompeted by the parental strain, indicating that the intracellular inositol metabolism confers a fitness advantage to the pathogen. Indeed, inositol added to
L. pneumophila
-infected amoebae or macrophages promoted intracellular growth of the parental strain, but not of the Δ
iolT
or Δ
iolG
mutant, and growth stimulation by inositol was restored by complementation of the mutant strains. The expression of the P

iol

promoter and bacterial uptake of inositol required the alternative sigma factor RpoS, a key virulence regulator of
L. pneumophila
. Finally, the parental strain and Δ
iolG
mutant bacteria but not the Δ
iolT
mutant strain accumulated [U-
14
C
6
]inositol, indicating that IolT indeed functions as an inositol transporter. Taken together, intracellular
L. pneumophila
metabolizes inositol through the
iol
gene products, thus promoting the growth and virulence of the pathogen.

IMPORTANCE
The environmental bacterium
Legionella pneumophila
is the causative agent of a severe pneumonia termed Legionnaires' disease. The opportunistic pathogen replicates in protozoan and mammalian phagocytes in a unique vacuole. Amino acids are thought to represent the prime source of carbon and energy for
L. pneumophila
. However, genome, transcriptome, and proteome studies indicate that the pathogen not only utilizes amino acids as carbon sources but possesses broader metabolic capacities. In this study, we analyzed the metabolism of inositol by extra- and intracellularly growing
L. pneumophila
. By using genetic, biochemical, and cell biological approaches, we found that
L. pneumophila
accumulates and metabolizes inositol through the
iol
gene products, thus promoting the intracellular growth, virulence, and fitness of the pathogen. Our study significantly contributes to an understanding of the intracellular niche of a human pathogen.
Hypertension in autosomal dominant polycystic kidney disease: a meta-analysis
Authors: Marlais Matko , Cuthell Oliver , Langan Dean , Dudley Jan , Sinha Manish D , Winyard Paul J D
Published: June 2016

Context

Autosomal dominant polycystic kidney disease (ADPKD) is a common disorder that can cause hypertension during childhood, but the true prevalence of hypertension during childhood is not known.

Objective

We undertook a systematic review and meta-analysis to determine the prevalence of hypertension in children with ADPKD.

Data sources

Systematic review of articles published between 1980 and 2015 in MEDLINE and EMBASE.

Study selection

Studies selected by two authors independently if reporting data on prevalence of hypertension in children and young persons aged <21 years with a diagnosis of ADPKD. Observational series were included with study populations of >15 children. Articles were excluded if inadequate diagnostic criteria for hypertension were used. Studies with selection bias were included but analysed separately.

Data extraction

Data extracted on prevalence of hypertension, proteinuria and reduced renal function using standardised form. Meta-analysis was performed to calculate weighted mean prevalence.

Results

903 articles were retrieved from our search; 14 studies met the inclusion criteria: 1 prospective randomised controlled trial; 8 prospective observational studies; and 5 retrospective cross-sectional studies. From 928 children with clinically confirmed ADPKD, 20% (95% CI 15% to 27%) were hypertensive. The estimated prevalence of proteinuria in children with ADPKD is 20% (8 studies; 95% CI 9% to 40%) while reduced renal function occurred in 8% (5 studies; 95% CI 2% to 26%).

Limitations

Studies showed a high degree of methodological heterogeneity (I2=73.4%, τ2=0.3408, p<0.0001). Most studies did not use ambulatory blood pressure (BP) monitoring to diagnose hypertension.

Conclusions

In this meta-analysis we estimate 20% of children with ADPKD have hypertension. In the population, many children with ADPKD are not under regular follow-up and remain undiagnosed. We recommend that all children at risk of ADPKD have regular BP measurement.
The impact of 12 months treatment with ivacaftor on Scottish paediatric patients with cystic fibrosis with the G551D mutation: a review
Authors: Dryden Carol , Wilkinson Jane , Young David , Brooker Richard John
Published: June 2016

We reviewed the impact of ivacaftor on Scottish paediatric patients with cystic fibrosis ≥6 years of age after 12 months of treatment. Statistically significant improvements in FEV1 and body mass index and a reduction in sweat chloride, all comparable with previously published data were observed. The findings also suggested reduced use of intravenous antibiotics and oral antibiotics. No significant adverse effects were observed but a possible association with cataract formation could not be excluded. This review suggests that, in the short term at least, ivacaftor is effective and safe in paediatric patients ≥6 years of age with G551D.
Poverty-Related Diseases College: a virtual African-European network to build research capacity
Authors: Dorlo Thomas P C , Fernández Carmen , Troye-Blomberg Marita , de Vries Peter J , Boraschi Diana , Mbacham Wilfred F
Published: June 2016

The Poverty-Related Diseases College was a virtual African-European college and network that connected young African and European biomedical scientists working on poverty-related diseases. The aim of the Poverty-Related Diseases College was to build sustainable scientific capacity and international networks in poverty-related biomedical research in the context of the development of Africa. The Poverty-Related Diseases College consisted of three elective and mandatory training modules followed by a reality check in Africa and a science exchange in either Europe or the USA. In this analysis paper, we present our experience and evaluation, discuss the strengths and encountered weaknesses of the programme, and provide recommendations to policymakers and funders.