bluuebunny/crossref_metadata_2025 huggingface dataset:
The Early Bronze Age of the Southern Caucasus
Authors: Palumbi Giulio
Published: October 2016

The aim of this article is to highlight the social and cultural developments that took place in the Southern Caucasus during the Early Bronze Age. Between 3500 and 2500 BC ca., new pottery, architectural and metallurgical traditions, known collectively as Kura-Araxes, new settlement forms in the mountain regions and new funerary customs emerged. Examining these changes, the article draws a picture of the organization of the Early Bronze Age communities in the Southern Caucasus societies centering primarily on the household and horizontal kinship relationships. We argue that this model was radically different from those of the vertically organized societies of Southern Mesopotamia and Northern Caucasus. Finally, the paper focuses on the changing role of metals towards the mid-third millennium BC and that, by causing radical social transformations, also brought to an end the Kura-Araxes traditions.
The Ongoing Psychological Colonization of North American Indigenous People: Using Social Psychological Theories to Promote Social Justice
Authors: Fryberg Stephanie , Covarrubias Rebecca , Burack Jacob A.
Published: October 2016

Colonizing events of the past and present continue to disrupt and change the cultural practices, histories, families, and languages of North American Indigenous peoples. As a result, Indigenous people experience a cultural disconnect between the past and the future, what we refer to as a disruption of traditional cultural cycles, in ways that foster psychological risks. In this chapter, we first discuss how the ongoing colonization of Indigenous people in contemporary society, with specific examples from the media and education, undermines psychological well-being. Second, we offer a theory of culture change as a “promotion” approach to target and mend the cultural disruptions brought on by colonizing practices and thereby to improve well-being. Finally, we offer research-based action items for social psychologists and for society more generally to alleviate the ongoing colonization of Indigenous people.
Positive Freedom and the General Will
Authors: Bringhurst Piper L. , Gaus Gerald
Published: October 2016

This chapter shows how one understanding of positive liberty—freedom as reasoned control—is presupposed by relations of moral responsibility. Rousseau’s “quixotic quest”—insuring that all subjects of the moral law remain morally free—is necessary to maintain responsibility relations within a moral community. Unless all are free to exercise reasoned control in accepting moral demands, they cannot be held responsible for failure to comply. We then inquire whether the concept of the general will can reconcile positive freedom and moral responsibility with regulation by a common moral law. Rousseau’s account seems inappropriate for a deeply diverse society because it holds that the general will arises from an essential identity of citizens’ interests. Instead, Bosanquet’s work suggests two contemporary proposals for ways in which a diverse society might share a general will, explaining in turn how its members are all fit to be held responsible for violating its moral rules.
Under-reporting of Risky Drug Use Among Primary Care Patients in Federally Qualified Health Centers
Authors: Bone Curtis , Gelberg Lilian , Vahidi Mani , Leake Barbara , Yacenda-Murphy Julia , Andersen Ronald M.
Published: October 2016

Objective:

The Affordable Care Act encourages integration of behavioral health into primary care. We aim to estimate the level of under-reporting of drug use in federally qualified health centers (FQHCs) among self-reported risky drug users.

Methods:

Adult patients in the waiting rooms of 4 FQHCs who self-reported risky drug use on the screening instrument World Health Organization's Alcohol, Smoking and Substance Involvement Screening Test (score 4–26), who participated in the “Quit Using Drugs Intervention Trial,” submitted urine samples for drug testing. Under-reporters were defined as patients who denied use of a specific drug via questionnaire, but whose urine drug test was positive for that drug. Descriptive statistics, Pearson chi-square test, and logistic regression were used for analysis.

Results:

Of the 192 eligible participants, 189 (96%) provided urine samples. Fifty-four samples were negative or indeterminate, yielding 135 participants with positive urine drug tests for this analysis: 6 tested positive for amphetamines, 18 opiates, 21 cocaine, 97 marijuana. Thirty patients (22%) under-reported drug use and 105 (78%) reported drug use accurately. Under-reporting by specific substances was: amphetamines 66%, opiates 45%, cocaine 14%, and marijuana 7%. Logistic regression revealed that under-reporting of any drug was associated with history of incarceration and older age (odds ratios 2.6 and 3.3, respectively; P < 0.05).

Conclusions:

Under-reporting of drug use is prevalent even among self-reported drug users in primary care patients of FQHCs (22%), but varied considerably based on the substance used. Further research is indicated to assess the extent of under-reporting among all primary care patients, regardless of their self-reported drug use status.
Cannabis as Secondary Drug Is Not Associated With a Greater Risk of Death in Patients With Opiate, Cocaine, or Alcohol Dependence
Authors: Fuster Daniel , Sanvisens Arantza , Bolao Ferran , Zuluaga Paola , Rivas Inmaculada , Farré Magi , Tor Jordi , Muga Robert
Published: October 2016

Background:

The health burden of cannabis use in patients with other substance dependencies is not fully understood.

Objective:

To assess the impact of cannabis use as secondary drug on mortality of patients with other major substance use disorders.

Participants:

Patients with opiate, cocaine, or alcohol dependence admitted to detoxification from 2001 to 2010 at a teaching hospital in Badalona, Spain.

Main Measurements:

Sociodemographic characteristics, drug use, medical comorbidities, and urine drug screens were obtained at admission. Deaths were ascertained through clinical records and a death registry. Mortality rates and Cox regression models were used to analyze the association between urinary cannabis and mortality.

Results:

A total of 474 patients (20% women) were admitted with a median age of 38 years (interquartile range: 32–44 years). The main substances that motivated admissions were opiates (27%), cocaine (24%), and alcohol (49%). Positive urinary cannabis was detected in 168 patients (35%). Prevalence of cannabis use among patients with opiate, cocaine, or alcohol dependence was 46.5%, 42.9%, and 25.5%, respectively. At admission, 110 (23.7%) patients had human immunodeficiency virus infection and 217 (46.5%) had hepatitis C virus infection. Patients were studied for a median of 5.6 years (interquartile range: 2.6–7.7 years) (2454.7 person-years), and at the end of the study, 50 patients (10.5%) had died, yielding a mortality rate of 2.04 × 100 patient-years (95% confidence interval: 1.53–2.66). There was no association between cannabis detection and overall mortality in the adjusted regression models [hazard ratio (95% confidence interval): 1.12 (0.60–2.00), P = 0.73], but acquired immune deficiency syndrome-related deaths were more frequent in those positive for cannabis (26% vs 2%, P = 0.03).

Conclusion:

Positive urinary cannabis did not confer an increased risk of death in patients with severe opiate, cocaine or alcohol dependence.
Erectile Dysfunction Among Patients on Methadone Maintenance Therapy and Its Association With Quality of Life
Authors: Teoh Joni Bing Fei , Yee Anne , Danaee Mahmoud , Ng Chong Guan , Sulaiman Ahmad Hatim Bin
Published: October 2016

Objectives:

Erectile dysfunction (ED) is a problem commonly encountered by patients on methadone maintenance therapy (MMT). This study aimed to assess the prevalence of ED among this group of patients along with its risk factors and association with quality of life (QOL).

Methods:

Male patients on MMT in a tertiary hospital in Malaysia were included in the study. A total of 134 patients with sexual partners were assessed for ED using the International Index of Erectile Function. Patients were assessed for substance use using Opiate Treatment Index (OTI) and depression using the Malay version of the self-rated Montgomery-Asberg Depression Rating Scale (MADRS-BM). QOL was evaluated using World Health Organisation Quality of Life (WHOQOL)-BREF.

Results:

The prevalence of ED among patients on MMT was 67%, with 26.1% having mild ED, 30.4% having mild-to-moderate ED, 7.0% having moderate ED, and 17.2% having severe ED. Patients with depression were 4 times more likely to have ED compared with patients without depression, whereas increasing age significantly correlated with the severity of ED. Having ED predicted a poorer QOL in the social relationships domain.

Conclusion:

Depression is highly associated with ED, which negatively influences the social aspect of QOL among patients on methadone maintenance therapy.
Efficacy and Safety of Once-Daily Controlled-Release Pregabalin for the Treatment of Patients With Postherpetic Neuralgia
Authors: Huffman Cynthia L. , Goldenberg James N. , Weintraub James , Sanin Luis , Driscoll Joseph , Yang Ruoyong , Chew Marci L. , Scavone Joseph M.
Published: October 2016

Objectives:

To assess efficacy and safety of once-daily controlled-release (CR) formulation of pregabalin in patients with postherpetic neuralgia.

Methods:

An enriched enrollment, randomized withdrawal trial, with 6-week single-blind pregabalin treatment phase and 13-week double-blind phase, where patients with ≥50% decrease in mean pain score at single-blind end point from baseline were randomized (1:1) to pregabalin CR (82.5 to 660 mg/d) or placebo. Primary efficacy outcome was time to loss of therapeutic response (LTR) (<30% decrease in weekly mean pain score from single-blind baseline or discontinuation due to adverse event or lack of efficacy). Secondary efficacy outcomes included change in weekly mean pain score (1-wk recall period) at double-blind end point.

Results:

In total, 801 patients were randomized and treated in the single-blind phase, and 413 in the double-blind phase (208, pregabalin CR; 205, placebo). Pregabalin CR significantly increased time to LTR versus placebo (Kaplan-Meier analysis) with significantly fewer LTR events with pregabalin CR than with placebo (29 [13.9%] vs. 63 [30.7%]; P<0.0001). Median time to LTR was not estimable. Pregabalin CR significantly improved weekly mean pain score versus placebo: LS mean difference (95% CI) of −1.11 (−1.47, −0.75) and −1.00 (−1.34, −0.65) (P<0.0001) from single-blind baseline and double-blind baseline, respectively. Most commonly reported adverse events in the single-blind phase were dizziness, somnolence, and peripheral edema. Pregabalin CR was well tolerated.

Discussion:

Time to LTR was significantly longer with pregabalin CR than with placebo. Safety profile of pregabalin CR was comparable to that reported for the immediate-release formulation in patients with postherpetic neuralgia.
Dose–response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man
Authors: Heerdt Paul M. , Sunaga Hiroshi , Owen Joel S. , Murrell Matthew T. , Malhotra Jaideep K. , Godfrey Deena , Steinkamp Michelle , Savard Peter , Savarese John J. , Lien Cynthia A.
Published: October 2016

Background

CW002 is a benzylisoquinolinium nondepolarizing neuromuscular-blocking drug found to be inactivated by cysteine in preclinical studies. The current study represents a dose escalation clinical trial designed to describe CW002 potency, duration, cardiopulmonary side effects, and histamine release.

Methods

Healthy subjects anesthetized with sevoflurane/nitrous oxide were divided into five groups (n = 6), each receiving a fixed CW002 dose (0.02, 0.04, 0.06, 0.08, or 0.10 mg/kg), and one group (n = 4) receiving 0.14 mg/kg. Blood pressure and heart rate were continuously recorded along with airway dynamic compliance. Neuromuscular blockade was assessed with mechanomyography at the adductor pollicis. Arterial blood was obtained before and after CW002 injection for analysis of plasma histamine concentration. Potency was estimated from a baseline sigmoid Emax model.

Results

ED50 was found to be 0.036 mg/kg (95% CI, 0.020 to 0.053 mg/kg) and ED95 0.077 mg/kg (95% CI, 0.044 to 0.114 mg/kg). At 0.14 mg/kg (1.8 × ED95), 80% twitch depression occurred in 94 ± 18 s with complete block in 200 ± 87 s. Clinical recovery (25% of maximum twitch) occurred in 34 ± 3.4 min, with a 5 to 95% recovery interval of 35.0 ± 2.7 min. The time to a train-of-four ratio greater than 0.9 ranged from 59 to 86 min. CW002 did not elicit histamine release or significant (greater than 10%) changes in blood pressure, heart rate, or dynamic airway compliance.

Conclusions

In healthy subjects receiving sevoflurane/nitrous oxide, CW002 at 1.8 × estimated ED95 produces a clinical duration less than 40 min, elicits no histamine release, and has minimal cardiopulmonary side effects.
Evaluation of the Effects of Physical Activity, Cardiorespiratory Condition, and Neuromuscular Fitness on Direct Healthcare Costs and Sickness-Related Absence Among Nursing Personnel With Recurrent Nonspecific Low Back Pain
Authors: Kolu Päivi , Tokola Kari , Kankaanpää Markku , Suni Jaana
Published: October 2016

Study Design.

A cross-sectional study, part of a randomized controlled trial.

Objective.

To evaluate the association of physical activity, cardiorespiratory fitness, and neuromuscular fitness with direct healthcare costs and sickness-related absence among nursing personnel with nonspecific low back pain.

Summary of Background Data.

Low back pain creates a huge economic burden due to increased sick leave and use of healthcare services.

Methods.

Female nursing personnel with nonspecific low back pain were included (n = 219). Physical activity was assessed with accelerometry and a questionnaire. In addition, measurements of cardiorespiratory and muscular fitness were conducted. Direct costs and sickness-related absence for a 6-month period were collected retrospectively by questionnaire. Health care utilization and absence from work were analyzed with a general linear model.

Results.

The mean total costs were 80.5% lower among women who met physical activity recommendations than inactive women. Those with a higher mean daily intensity level of 10-minute activity sessions showed lower total costs than women in the lowest tertile (middle: 64.0% of the lowest; highest: 54.3% of the lowest). Women with good cardiorespiratory fitness (the highest tertile) as measured with the 6-minute-walk test (based on walking distance) had 77.0% lower total costs when compared with the lowest tertile. Women in the highest third for the modified push-up test had 84.0% lower total costs than those with the poorest results (the bottom tertile).

Conclusion.

High cardiorespiratory and muscular fitness and meeting physical activity recommendations for aerobic and muscular fitness were strongly associated with lower total costs among nursing personnel with pain-related disorders of recurrent nonspecific low back pain. Actions to increase physical activity and muscle conditioning may significantly save on healthcare costs and decrease sick-leave costs due to low back pain.

Level of Evidence: 3
Prospective evaluation of prognostic indicators for early recurrence of cutaneous melanoma
Authors: Matheson Julia A.H. , te Marvelde Luc , Mailer Sonia , Speakman David , Spillane John , Henderson Michael A. , Gyorki David E.
Published: October 2016

The majority of melanomas are thin lesions with an excellent prognosis; however, significant tumor heterogeneity exists, and a small percentage of patients with early-stage disease may progress to metastatic recurrence. This study aimed to assess whether prognostic factors previously shown to be significant in predicting stage I and stage II melanoma recurrence were consistent in a large prospectively collected patient cohort, and to identify novel prognostic factors associated with early recurrence to inform follow-up protocols. There were 1029 patients with stage I and stage II melanoma included in the analysis, of whom 123 developed a recurrence during follow-up (median 2.13 years). Multivariable analysis identified ulceration, presence of mitoses, Clark level, presence of lymphovascular invasion, and a history of autoimmune disease as factors independently associated with recurrence. These data identified patients with stage I–II melanoma with very low-risk for recurrence: no ulceration, zero mitoses, a low Clark level, no lymphovascular invasion, and possibly no history of autoimmune disease. These patients do not require intensive follow-up: 12 monthly reviews and full skin checks may be appropriate. Ongoing research into prognostic factors for recurrence in early-stage melanoma is important.
The Plastic Surgeon at Work and Play: Surgeon Health, Practice Stress, and Work–Home Balance
Authors: Bentz Michael L.
Published: October 2016

Plastic surgeon wellness encompasses physical and mental health, considered in the context of practice stress. In addition, the challenges of work–home balance can lead to substantial negative impact on the surgeon, family, staff, and patients. The data-driven impact of each of these three components with personal vignettes, both individually and collectively, is presented by Michael Bentz, MD as the 2016 presidential address of American Association of Plastic Surgeons.
BILATERAL INTRAOCULAR HEMORRHAGE SECONDARY TO CEREBRAL VENOUS SINUS THROMBOSIS
Authors: Kunle-Hassan Feyi , Dattani Minaxi , Snead Martin , Subash Mala
Published: October 2016

Purpose:

To report a case of bilateral intraocular hemorrhage secondary to cerebral venous sinus thrombosis with no associated intracranial hemorrhage.

Methods:

Case report.

Results:

A 32-year-old Asian gentleman presented with left reduced vision as a result of a left subhyaloid macular hemorrhage associated with severe headache. Right retinal hemorrhages were also present. Magnetic resonance imaging and computed tomography brain imaging demonstrated cerebral transverse venous sinus thrombosis.

Conclusion:

Intraocular hemorrhage has previously been described in association with intracranial hemorrhage and in particular subarachnoid hemorrhage (Terson syndrome). We describe a similar clinical picture in the context of cerebral venous sinus thrombosis with no associated intracranial hemorrhage.
Nodulo-Ulcerative Ocular Surface Squamous Neoplasia in 6 Patients: A Rare Presentation
Authors: Kaliki Swathi , Freitag Suzanne K. , Chodosh James
Published: October 2016

Purpose:

To describe clinical presentation and histopathological features of a nodulo-ulcerative variant of ocular surface squamous neoplasia (OSSN).

Methods:

Retrospective study.

Results:

Six patients were identified with a nodulo-ulcerative variant of OSSN. Mean age at presentation was 56 years. One patient was immunosuppressed because of human immunodeficiency virus infection. The initial misdiagnosis was necrotizing scleritis/sclerokeratitis (n = 4), intraepithelial neoplasia (n = 1), and chalazion (n = 1). The mean delay in diagnosis as OSSN was 6 months. The lesion involved bulbar conjunctiva in 5 patients and tarsal conjunctiva in 1 patient. The mean maximum tumor dimension was 16 mm, and the mean area of conjunctivoscleral/conjunctivotarsal necrosis was 8 mm. The primary treatment for nodulo-ulcerative OSSN included excisional biopsy (n = 2), plaque radiotherapy (n = 1), and orbital exenteration (n = 3). Tumor recurrence was noted in two patients necessitating orbital exenteration. At last follow-up, globe salvage could be achieved in only 1 case. Histopathology showed invasive conjunctival squamous cell carcinoma in all cases with lesions being well-differentiated (n = 4), moderately differentiated (n = 1), and with mucoepidermoid differentiation (n = 1). Underlying scleral/tarsal tumor infiltration was evident in all 6 (100%) cases. Intraocular tumor extension was evident in 3 cases infiltrating the iris (n = 2), ciliary body (n = 3), and choroid (n = 3). Orbital tumor extension was evident in 2 cases because of tumor recurrence. No metastasis or death was recorded at a mean follow-up of 26 months.

Conclusions:

The nodulo-ulcerative variant of OSSN is rare and is most often misdiagnosed as necrotizing scleritis/sclerokeratitis causing a delay in the diagnosis. It is an aggressive lesion with increased occurrence of intraocular or orbital tumor extension.
Kojic Acid
Authors: Gust Peter J. , Luke Janiene D.
Published: October 2016

A drug is defined in physiology as being a substance that exerts an effect on the body once it has been ingested. Drugs take many forms in their attempt to enter the body including capsules, injections, creams, ointments, inhalants, liquids, and dermal patches. The purpose of this column is to take a closer look at drugs that are used in the field of dermatology. More specifically, this column hopes to bring an understanding to the reader regarding mechanism of action, administration, dosage, adverse effects, and viable alternatives to each particular drug being discussed. In this article, the role of the drug kojic acid, as a dermatologic treatment for hyperpigmentation disorders, as well as other novel uses will be discussed.
Itchy Blisters and Pink Bumps on the Hands and Elbows
Authors: So Jessica Kim , Jacob Sharon E.
Published: October 2016

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. In this modality, there is transfer of patient medical information electronically (including history and visual data) obtained in one location to a provider who is in another location (Roman & Jacob, 2015). The construct of the TeleDermViewPoint column is such that cases are presented in a standardized teledermatology reader format reflective of an actual teledermatology report. This is a case of itchy blisters and pink bumps on the hands and elbows.
Racial Discrimination and Psychological Wellbeing of Pregnant Women
Authors: Giurgescu Carmen , Zenk Shannon N. , Engeland Christopher G. , Garfield Lindsey , Templin Thomas N.
Published: October 2016

Purpose:

African American women are more likely to be exposed to racial discrimination and to experience psychological distress compared with white women. Although studies have shown that social support is positively related to psychological wellbeing, little is known about the potential buffering effect of social support on the relationship between racial discrimination and psychological wellbeing of pregnant women. The purpose of this study was to determine if social support moderates effects of racial discrimination on psychological wellbeing among pregnant African American women.

Study Design and Methods:

Using a cross-sectional design, 107 African American women between 15 and 26 weeks gestation from an urban university-based midwifery practice completed questionnaires.

Results:

Women who reported more experiences of racial discrimination also reported lower levels of social support and psychological wellbeing (p <.05).

Clinical Implications:

Maternal child nurses should be aware that experiences of racial discrimination have negative effects on psychological wellbeing of pregnant African American women regardless of their levels of social support. However, social support can reduce psychological distress and improve wellbeing of pregnant women. Therefore, nurses need to provide pregnant women with positive and supportive experiences that may improve their psychological wellbeing.
The Cost-efficiency and Care Effectiveness of Probiotic Administration with Antibiotics to Prevent Hospital-Acquired Clostridium difficile Infection
Authors: Starn Emily S. , Hampe Holly , Cline Thomas
Published: October 2016

Health care facility–acquired Clostridium difficile infections (HCFA-CDI) have increased over the last several decades despite facilities developing protocols for prescribing probiotics with antibiotics to prevent HCFA-CDI. The literature does not consistently support this. A retrospective medical record review evaluated the care effectiveness of this practice. Care effectiveness was not found; patients receiving probiotics with antibiotics were twice as likely to develop HCFA-CDI (P = .004). Except with glycopeptides, patients were 1.88 times less likely to experience HCFA-CDI (P = .05).
Percutaneous Lung Biopsy in the Molecular Profiling Era
Authors: Lee Christopher , Guichet Phillip L. , Abtin Fereidoun
Published: October 2016

Purpose:

This study aimed to assess the current practice patterns of radiologists performing percutaneous lung biopsies.

Materials and Methods:

This cross-sectional study used a web-based survey sent to the Society of Thoracic Radiology membership from August to October 2015. Responses were collected anonymously, and results were tallied.

Results:

A total of 244 Society of Thoracic Radiology members responded to the survey. One hundred thirty-seven radiologists regularly perform percutaneous lung biopsies, of whom 102 (74%) practice at an academic teaching hospital. Computed tomography (CT) and CT fluoroscopy were the modalities of choice for image guidance, preferred by 82 (60%) and 48 (35%) respondents, respectively. Twenty (15%) respondents preferred fine-needle aspiration (FNA) alone, 57 (42%) preferred core needle biopsy (CNB) alone, and 59 (43%) preferred both FNA and CNB in the same setting. On-site cytology was routinely requested by 70 (71%) respondents with access to such services. In cases of suspected lung cancer, 79 (60%) respondents estimated sending tissue for molecular analysis >25% of the time. Forty-three (32%) respondents reported using intraprocedural preventive measures to minimize risk of pneumothorax.

Conclusions:

Among surveyed radiologists who perform percutaneous lung biopsies, most utilize CT guidance with either CNB alone or in conjunction with FNA. A small minority routinely performs FNA alone, which may negatively impact diagnostic accuracy and provide insufficient tissue for molecular profiling. Education of all radiologists regarding the importance of routinely acquiring and sending greater amounts of tissue for molecular/genomic assessment of suspected lung cancer is needed.
Extensive Horizontal Gene Transfer in Cheese-Associated Bacteria
Authors: Bonham Kevin S. , Wolfe Benjamin E. , Dutton Rachel J.
Published: October 2016

Acquisition of genes through horizontal gene transfer (HGT) allows microbes to rapidly gain new capabilities and adapt to new or changing environments. Identifying widespread HGT regions within multispecies microbiomes can pinpoint the molecular mechanisms that play key roles in microbiome assembly. We sought to identify horizontally transferred genes within a model microbiome, the cheese rind. Comparing 31 newly-sequenced and 134 previously sequenced bacterial isolates from cheese rinds, we identified over 200 putative horizontally transferred genomic regions containing 4,733 protein coding genes. The largest of these regions are enriched for genes involved in siderophore acquisition, and are widely distributed in cheese rinds in both Europe and the US. These results suggest that horizontal gene transfer (HGT) is prevalent in cheese rind microbiomes, and the identification of genes that are frequently transferred in a particular environment may provide insight into the selective forces shaping microbial communities.
A dual-strategy expression screen for candidate connectivity labels in the developing thalamus
Authors: Bibollet-Bahena Olivia , Okafuji Tatsuya , Hokamp Karsten , Mitchell Kevin J.
Published: October 2016

The thalamus or “inner chamber” of the brain is divided into ~30 discrete nuclei, with highly specific patterns of afferent and efferent connectivity. To identify genes that may direct these patterns of connectivity, we used two strategies. First, we used a bioinformatics pipeline to survey the predicted proteomes of nematode, fruitfly, mouse and human for extracellular proteins containing any of a list of motifs found in known guidance or connectivity molecules. Second, we performed clustering analyses on the Allen Developing Mouse Brain Atlas data to identify genes encoding surface proteins expressed with temporal profiles similar to known guidance or connectivity molecules. In both cases, we then screened the resultant genes for selective expression patterns in the developing thalamus. These approaches identified 82 candidate connectivity labels in the developing thalamus. These molecules include many members of the Ephrin, Eph-receptor, cadherin, protocadherin, semaphorin, plexin, Odz/teneurin, Neto, cerebellin, calsyntenin and Netrin-G families, as well as diverse members of the immunoglobulin (Ig) and leucine-rich receptor (LRR) superfamilies, receptor tyrosine kinases and phosphatases, a variety of growth factors and receptors, and a large number of miscellaneous membrane-associated or secreted proteins not previously implicated in axonal guidance or neuronal connectivity. The diversity of their expression patterns indicates that thalamic nuclei are highly differentiated from each other, with each one displaying a unique repertoire of these molecules, consistent with a combinatorial logic to the specification of thalamic connectivity.
Measuring the criticality of the `magic condition' for a beam-expanding monochromator
Authors: Martinson Mercedes , Chapman Dean
Published: October 2016

It has been established that for cylindrically bent crystals the optimal beam characteristics occur when the geometric and single-ray foci are matched. In the beam-expanding monochromator developed for the BioMedical Imaging and Therapy beamlines at the Canadian Light Source, it was unclear how critical this `magic condition' was for preserving the transverse coherence of the beam. A study was conducted to determine whether misalignments away from the ideal conditions would severely affect the transverse coherence of the beam, thereby limiting phase-based imaging techniques. The results were that the magic condition has enough flexibility to accommodate deviations of about ±1° or ±5 keV.
Comparison of thallium(I) complexes with mesityl-substituted tris(pyrazolyl)hydroborate ligands, [Tl{HB(3-Ms-5-Mepz)3}] and [Tl{HB(3-Ms-5-Mepz)2(3-Me-5-Mspz)}]
Authors: Fujisawa Kiyoshi , Shimizu Masaya , Szilagyi Robert K.
Published: October 2016

Tris(pyrazolyl)borate (scorpionate) ligands can be considered as the most prolific ligands in contemporary coordination chemistry due to the availability of various steric and electronic substituents at the pyrazolyl rings that allow fine-tuning of the open-coordination site for metal centres. The thallium(I) complexes of anionic tridentate-chelating scorpionate ligands, namely [tris(3-mesityl-5-methyl-1H-pyrazol-1-yl-κN2)hydroborato]thallium(I) monohydrate, [Tl(C39H46BN6)]·H2O, (I), and [bis(3-mesityl-5-methyl-1H-pyrazol-1-yl-κN2)(5-mesityl-3-methyl-1H-pyrazol-1-yl-κN2)hydroborato]thallium(I), [Tl(C39H46BN6)], (II), show a {TlIN3} coordination, with average TlI—N bond lengths of 2.53 and 2.55 Å in (I) and (II), respectively. The overall TlIcoordination geometry is distorted trigonal pyramidal, with the average N—TlI—N angle being approximately 73° for both. The dihedral angle between the planes of the pyrazolyl and benzene rings of the mesityl group is 82° in (I), while the corresponding angles in (II) are in the range 64–104°. The structural differences between the two ligands are expected to contribute to the different reactivities of the transition metal coordination complexes towards activation of small molecules such as dioxygen and ethylene.
Steric and electronic factor comparisons in hydrotris(3-phenylpyrazolyl)borate nickel(II) aryloxides
Authors: Green William L. , Sirianni Eric R. , Yap Glenn P. A. , Riordan Charles G.
Published: October 2016

Hydrotris(pyrazolyl)borate (Tp) ligands, also known as scorpionates, are potent tridentate donors that effectively bind metal ions in a face-capping array. Hydrotris(3-phenylpyrazolyl)borate enforces a tetrahedral environment on NiIIto model metalloenzymes. The syntheses and structural characterizations of a number of [hydrotris(3-phenylpyrazolyl)borato]nickel(II) aryloxides were performed to provide insight into the environment of the model active site; these compounds are chlorido[hydrotris(3-phenylpyrazolyl-κN2)borato](3-phenyl-1H-pyrazole-κN2)nickel(II) chloroform monosolvate, [Ni(C27H22BN6)Cl(C9H8N2)]·CHCl3, (2), [hydrotris(3-phenylpyrazolyl-κN2)borato](phenolato-κO)nickel(II), [Ni(C27H22BN6)(C6H5O)], (3), (2,6-dimethylphenolato-κO)[hydrotris(3-phenylpyrazolyl-κN2)borato]nickel(II) [Ni(C27H22BN6)(C8H9O)], (4), (4-tert-butylphenolato-κO)[hydrotris(3-phenylpyrazolyl-κN2)borato]nickel(II), [Ni(C27H22BN6)(C10H13O)], (5), and [hydrotris(3-phenylpyrazolyl-κN2)borato](phenolato-κO)(tetrahydrofuran-κO)nickel(II) tetrahydrofuran monosolvate, [Ni(C27H22BN6)(C6H5O)(C4H8O)]·C4H8O, (6). Alkyl groups,e.g. tert-butyl in (5) and methyl in (4), electronically activate the aryloxide group to intramolecular π–π stacking but can be frustrated by steric encumbrance at the interacting ring faces. The flexibility at the nickel coordination site, afforded by the uncrowded B atom of the TpPhligand, allows tetrahydrofuran coordination in the phenolate compound.
The silver(I) complex [HB{3-(CF3),5-(CH3)Pz}3]AgNCCH3supported by a partially fluorinated scorpionate ligand
Authors: Dias H. V. Rasika , Kulkarni Naveen
Published: October 2016

Tris(pyrazolyl)borates are used extensively in metal coordination chemistry and belong to a class of ligands generally referred to as scorpionates. The steric and electronic properties of these ligands can be modified quite easily by varying the substituents on the 3-, 4-, and 5-positions of the pyrazolyl moieties on the B atom. Fluorinated tris(pyrazolyl)borates are useful in the stabilization of rare silver(I) complexes. The silver(I) adduct (acetonitrile-κN){tris[5-methyl-3-(trifluoromethyl)pyrazol-1-yl-κN2]hydroborato}silver(I), [Ag(C15H13BF9N6)(CH3CN)] or [HB{3-(CF3),5-(CH3)Pz}3]AgNCCH3, was obtained by treating [HB{3-(CF3),5-(CH3)Pz}3]Na with CF3SO3Ag in the presence of acetonitrile, and was isolated in 85% yield. Single-crystal X-ray diffraction analysis reveals that the AgIcenter has a pseudo-tetrahedral all-nitrogen coordination sphere, and is supported by a tris(pyrazolyl)borate ligand that binds to the AgIcenter in a κ3-fashion.
Molecular structures of tris(1-tert-butyl-2-mercaptoimidazolyl)hydroborate complexes of titanium, zirconium and hafnium
Authors: Rong Yi , Sambade David , Parkin Gerard
Published: October 2016

Cyclopentadienyl and tris(pyrazolyl)hydroborate have found much use as supporting ligands in the chemistry of titanium, zirconium and hafnium, especially with respect to applications involving olefin polymerization catalysis. In contrast, closely related tris(1-alkyl-2-mercaptoimidazolyl)hydroborate, [TmR], ligands have so far found little application to the chemistry of these elements, despite the fact that such ligands are currently used extensively in coordination chemistry. In view of the fact that a substituent in the 2-position exerts a direct influence on the steric environment of the metal center, we report here the application of the sterically demanding tris(1-tert-butyl-2-mercaptoimidazolyl)hydroborate [Tm^{{\rm Bu}^{\rm t}}] ligand to these metals. Dichlorido(η5-cyclopentadienyl)[tris(1-tert-butyl-2-sulfanylidene-2,3-dihydro-1H-imidazol-3-yl)borato-κ3S,S′,H]zirconium(IV) benzene hemisolvate, [Zr(C21H34BN6S3)(C5H5)Cl2]·0.5C6H6, (I), dichlorido(η5-cyclopentadienyl)[tris(1-tert-butyl-2-sulfanylidene-2,3-dihydro-1H-imidazol-3-yl)borato-κ3S,S′,H]titanium(IV) benzene hemisolvate, [Ti(C21H34BN6S3)(C5H5)Cl2]·0.5C6H6, (II), [bis(1-tert-butyl-2-sulfanylidene-2,3-dihydro-1H-imidazol-3-yl)borato-κ3S,S′,H]dichlorido(η5-cyclopentadienyl)zirconium(IV), [Zr(C14H24BN4S2)(C5H5)Cl2], (III), (1-tert-butyl-2,3-dihydro-1H-imidazole-2-thione-κS)(1-tert-butyl-2-sulfanylidene-1H-imidazol-3-ido-κ2N3,S)dichlorido(η5-cyclopentadienyl)zirconium(IV) benzene monosolvate, [Zr(C7H11N2S)(C7H12N2S)(C5H5)Cl2]·C6H6, (IV), and tribenzyl[tris(1-tert-butyl-2-sulfanylidene-2,3-dihydro-1H-imidazol-3-yl)borato-κ3S,S′,S′′]hafnium(IV) benzene tetrasolvate, [Hf(C7H7)3(C21H34BN6S3)]·4C6H6, (V), have been structurally characterized by X-ray diffraction. The [Tm^{{\rm Bu}^{\rm t}}^{{\rm Bu}^{\rm t}}] ligand coordinates to Ti and Zr in Cp[κ3S2,H-Tm^{{\rm Bu}^{\rm t}}]MCl2[M = Zr, (I), and Ti, (II)] in a κ3S2,Hmode, while the benzyl compounds [Tm^{{\rm Bu}^{\rm t}}]M(CH2Ph)3[M = Zr and Hf, (V)] exhibit κ3S3coordination.
Side-on coordination mode of a pyrazolyl group in the structure of a divalent [Sm{B(3-Mepz)4}2] complex (3-Mepz is 3-methylpyrazol-1-yl)
Authors: Arikawa Yasuhiro , Inada Kei-ichiro , Onishi Masayoshi
Published: October 2016

The discovery of polypyrazolylborate ligands allowed the development of various chemical fields and these ligands are an alternative to cyclopentadienyl, because both ligands have the same charge and donate the same number of electrons, as well as adopting the same facial geometry. Easy control of the bulkiness of polypyrazolylborate ligands is possible by modification of the substituents in the 3- and 5-positions of the pyrazolyl rings. The title complex, bis[tetrakis(3-methyl-1H-pyrazol-1-yl)borato]samarium(II), [Sm(C16H20BN8)2], was synthesized from the reaction of SmI2with potassium tetrakis(3-methyl-1H-pyrazol-1-yl)borate, denoted K[B(3-Mepz)4], in tetrahydrofuran. The X-ray structure analysis revealed an unusual side-on coordination mode of a 3-methylpyrazolyl group through an N=N group in the B(3-Mepz)4ligand. The distortion is defined by the B—N—N—Sm torsion angle [85.5 (4)°]. This is in contrast to the structure of the similar divalent samarium complex [Sm(Tp^{{\rm Me}_2})2] [Tp^{{\rm Me}_2} is tris(3,5-dimethylpyrazol-1-yl)borate], which displays normal κ3-bonding modes of the Tp^{{\rm Me}_2} ligands.
New homodinuclear tris(3-alkylpyrazolyl)borate complexes of CoIIand NiIIwith a tetraacetylethane dianion as a bridging ligand
Authors: Mikhalyova Elena A. , Trofimenko Swiatoslaw , Zeller Matthias , Addison Anthony W. , Pavlishchuk Vitaly V.
Published: October 2016

Polynuclear complexes and coordination polymers of 3dmetals have attracted significant interest evoked by a number of their unique properties. One of the most common approaches to the directed synthesis of coordination polymers is the linking of pre-prepared discrete coordination units by polydentate ligands. The formation of polynuclear complexes is usually a spontaneous process and precise prediction of the products of such reactions is virtually impossible in most cases. Tris(pyrazolyl)borates (Tp) act as tripodal `capping' ligands which form stable complexes with 3dmetal ions. In such 1:1 compounds, three metal-ion coordination sites are occupied by N atoms from a Tp anion. This limits the number of remaining coordination sites, and thus the number of additional ligands which may coordinate, and opens an attractive approach for the directed design of desirable structures by exploiting ligands with appropriate composition and topology. In the present study, Tp anions with neopentyl [TpNp, tris(3-neopentylpyrazolyl)borate] and cyclohexyl [TpCy, tris(3-cyclohexylpyrazolyl)borate] substituents were used as `capping' ligands and the dianion of tetraacetylethane (3,4-diacetylhexa-2,4-diene-2,5-diolate, tae2−) was employed as a bridge. The dinuclear complexes (μ-3,4-diacetylhexa-2,4-diene-2,5-diolato-κ4O2,O3:O4,O5)bis{[tris(3-cyclohexyl-1H-pyrazol-1-yl-κN2)borato]cobalt(II)} acetonitrile disolvate, [Co2(C27H40BN6)2(C10H12O4)]·2CH3CN, (I)·2CH3CN, and (μ-3,4-diacetylhexa-2,4-diene-2,5-diolato-κ4O2,O3:O4,O5)bis{[tris(3-neopentyl-1H-pyrazol-1-yl-κN2)borato]nickel(II)}, [Ni2(C24H40BN6)2(C10H12O4)], (II), were synthesized by the reaction of the mononuclear complexes TpCyCoCl or TpNpNiCl with H2tae (3,4-diacetylhexane-2,5-dione or tetraacetylethane) in the presence of NEt3as base. Compounds (I) and (II) were characterized by mass spectrometry, elemental analysis, and X-ray crystallography. They possess similar molecular structures, X-ray diffraction revealing them to be dinuclear in nature and composed of discrete Tp–Munits in which two metal ions are linked by a tae2−dianion. Each metal ion possesses a five-coordinate square-pyramidal environment. The interplanar angles between the acetylacetonate fragments are significantly smaller than the near-90° values commonly observed.
The non-isomorphous crystal structures of NHC—Au—Cl and NHC—Au—Br (NHC is 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene)
Authors: Tacke Matthias , Dada Oyinlola , O'Beirne Cillian , Zhu Xiangming , Müller-Bunz Helge
Published: October 2016

Gold monochloride and monobromide can be transformed into monomeric complexes by ligands such as CO, PPh3or Me2S, and such ligand-stabilized gold monochloride compounds have been investigated as catalysts, luminescent materials and anticancer drugs, especially when coordinated to a lipophilic benzyl-substituted N-heterocyclic carbene (NHC) ligand. The triclinic structures of NHC–Au–Cl {chlorido(1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene)gold, [AuCl(C29H24N2)]} and NHC—Au—Br {bromido(1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene)gold, [AuBr(C29H24N2)]}, determined by X-ray crystallography at 100 K, have one and four molecules, respectively, in their asymmetric units. The chloride compound shows an almost linear C—Au—Cl fragment [179.76 (8)°], with an Au—C distance of 1.976 (3) Å and an Au—Cl distance of 2.3013 (6) Å, while the bromide compound shows surprisingly large geometry deviations, from 1.969 (12) to 2.016 (10) Å for the Au—C distance and from 2.4279 (14) to 2.4796 (12) Å for the Au—Br distance, in the four independent molecules.
An alternative to the goodness of fit
Authors: Henn Julian
Published: October 2016

An alternative measure to the goodness of fit (GoF) is developed and applied to experimental data. The alternative goodness of fit squared (aGoFs) demonstrates that the GoF regularly fails to provide evidence for the presence of systematic errors, because certain requirements are not met. These requirements are briefly discussed. It is shown that in many experimental data sets a correlation between the squared residuals and the variance of observed intensities exists. These correlations corrupt the GoF and lead to artificially reduced values in the GoF and in the numerical value of thewR(F2). Remaining systematic errors in the data sets are veiled by this mechanism. In data sets where these correlations do not appear for the entire data set, they often appear for the decile of largest variances of observed intensities. Additionally, statistical errors for the squared goodness of fit, GoFs, and the aGoFs are developed and applied to experimental data. This measure shows how significantly the GoFs and aGoFs deviate from the ideal value one.
Crystal structures of 6-chloroindan-1-one and 6-bromoindan-1-one exhibit different intermolecular packing interactions
Authors: Caruso Alessio , Blair Benjamin , Tanski Joseph M.
Published: October 2016

The two title compounds are analogs of 1-indanone that are substituted at the 6-position with chlorine and bromine. Although very similar in molecular structure, the crystal structures are not isomorphous and reveal that 6-chloroindan-1-one, C9H7ClO (I), and 6-bromoindan-1-one, C9H7BrO (II), exhibit unique intermolecular packing motifs. The molecules of the chloro analog (I) pack with a herringbone packing motif of C—H...O interactions, whereas the bromo derivative (II) packs with offset face-to-face π-stacking, C—H...O, C—H...Br and Br...O interactions. Compound (II) was refined as a two-component non-merohedral twin, BASF 0.0762 (5).
Crystal structure of rac-2,3-diphenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one 1-oxide
Authors: Yennawar Hemant P. , Yang Ziwei , Silverberg Lee J.
Published: October 2016

In the title compound, C16H15NO2S [alternative name: rac-2,3-diphenyl-1,3-thiazinan-4-one 1-oxide], the thiazine ring exhibits an envelope conformation, with the S atom forming the flap. The sulfoxide O atom is in a pseudo-axial position on the thiazine ring and is trans to the phenyl group on C-2. The phenyl rings form a dihedral angle of 89.47 (19)°. In this racemate crystal, homochiral molecules form slabs parallel to (010) of thickness b/2 which then stack with alternating chirality in the b-axis direction. The stacking is aided by edge-to-face interactions between the phenyl rings of racemic molecules. Within each of the single-enantiomer slabs, the molecules are held by C—H...O-type interactions, with an H...O distance of 2.30 Å, forming infinite chains along the c-axis direction, as well by the edge-to-face interactions between phenyl rings of neighboring molecules in the a-axis direction.
Crystal structure and Hirshfeld surface analysis of 1-carboxy-2-(3,4-dihydroxyphenyl)ethan-1-aminium bromide 2-ammonio-3-(3,4-dihydroxyphenyl)propanoate
Authors: Kathiravan Perumal , Balakrishnan Thangavelu , Venkatesan Perumal , Ramamurthi Kandasamy , Percino María Judith , Thamotharan Subbiah
Published: October 2016

In the title molecular salt, C9H12NO4
+·Br−·C9H11NO4, one of the dopa molecules is in the cationic form in which the α-amino group is protonated and the α-carboxylic acid group is uncharged, while the second dopa molecule is in the zwitterion form. The Br− anion occupies a special position and is located on a twofold rotation axis. The two dopa molecules are interconnected by short O—H...O hydrogen bonds. In the crystal, the various units are linked by O—H...O, N—H...Br and N—H...O hydrogen bonds, forming a three-dimensional framework. The title compound was refined as an inversion twin with an absolute structure parameter of 0.023 (8).
Cyclosporin a induces renal episodic hypoxia
Authors: Fähling M. , Mathia S. , Scheidl J. , Abramovitch R. , Milman Z. , Paliege A. , Peters H. , Persson P. B. , Heyman S. N. , Rosenberger C.
Published: October 2016

Aim

Cyclosporin A (CsA) causes renal toxicity. The underlying mechanisms are incompletely understood, but may involve renal hypoxia and hypoxia‐inducible factors (Hifs). We sought for hypoxia and Hif in mouse kidneys with CsA‐induced toxicity, assessed their time course, Hif‐mediated responses and the impact of interventional Hif upregulation.

Methods

Mice received CsA or its solvent cremophore for up to 6 weeks. Low salt diet (Na+↓) was given in combination with CsA to enhance toxicity. We assessed fine morphology, renal function, blood oxygen level‐dependent magnetic resonance imaging under room air and following changes in breathing gas composition which correlate with vascular reactivity, pimonidazole adducts (which indicate O2 tensions below 10 mmHg), Hif‐α proteins, as well as expression of Hif target genes. Stable Hif upregulation was achieved by inducible, Pax8‐rtTA‐based knockout of von Hippel–Lindau protein (Vhl‐KO), which is crucial for Hif‐α degradation.

Results

Cyclosporin A transiently increased renal deoxyhaemoglobin (R2*). Augmented vascular reactivity was observed at 2 h, but decreased at 24 h after CsA treatment. Na+↓/CsA provoked chronic renal failure with tubular degeneration and interstitial fibrosis. Nephron segments at risk for injury accumulated pimonidazole adducts, as well as Hif‐α proteins. Remarkably, Hif target gene expression remained unchanged, while factor‐inhibiting Hif (Fih) was enhanced. Na+↓/CsA/Vhl‐KO aggravated morpho‐functional outcome of chronic renal CsA toxicity.

Conclusions

Cyclosporin A provokes episodic hypoxia in nephron segments most susceptible to chronic CsA toxicity. Fih is upregulated and likely blocks further Hif activity. Continuous tubular Hif upregulation via Vhl‐KO worsens the outcome of chronic CsA‐induced renal toxicity.