bluuebunny/crossref_metadata_2025 huggingface dataset:
Letter to Renata Gaddini
Authors: Winnicott Donald W.
Published: March 2017

Letter from Winnicott to Renata Gaddini on the symptomatology of ‘hair-pulling’.
Review: Children in Distress
Authors: Winnicott Donald W. , Clegg Alec , Megson Barbara
Published: March 2017

Winnicott’s critical review of Megson and Clegg’s book Children in Distress. Focussing on the ‘good old bad immediate external factors’, he asserts it might as well be about the weather.
Clinical Illustration of ‘The Use of an Object’
Authors: Winnicott Donald W.
Published: March 2017

Winnicott uses a clinical case study to elaborate the hypothesis of his ‘Use of an Object’ paper. The inhibitions in the patient’s inner world and his struggle to deploy his instinctual energies satisfactorily are discussed.
Letter to Karl and Sheila Britton
Authors: Winnicott Donald W.
Published: March 2017

Winnicott’s letter to Karl and Sheila Britton from Lenox Hill Hospital in New York on his deteriorating heart condition.
Letter to Joyce Coles
Authors: Winnicott Donald W.
Published: March 2017

Winnicott writes from Lenox Hill Hospital in New York to his long-standing secretary Joyce Coles, taking care of some domestic administration.
Letter to Joyce Coles
Authors: Winnicott Donald W.
Published: March 2017

Winnicott writes from Lenox Hill Hospital in New York to his long-standing secretary Joyce Coles on the work ahead.
Comments on My Paper ‘The Use of an Object’
Authors: Winnicott Donald W.
Published: March 2017

Winnicott comments on the responses of colleagues in the New York Psychoanalytic Society to his paper ‘The Use of an Object’. He points out the developmental growth in this area of ‘object use’ for certain patients who need to ‘destroy their object in fantasy and see it survives in reality’. He also states that what here appears as ‘destructive’ in actuality is the vitality and energy of what it means to be alive. Through clinical work in this area, the analyst may become a real object, existing outside the patient’s omnipotent fantasises, something that is not usually possible in cases of more acute mental illness.
Letter to Karl Britton
Authors: Winnicott Donald W.
Published: March 2017

A letter from Winnicott while he was ill from the sudden onset of a serious heart condition in a New York Hospital to his brother-in-law Karl and his wife Sheila, expressing hope of a good recovery.
Letter to Joyce Coles
Authors: Winnicott Donald W.
Published: March 2017

Winnicott writes from Lenox Hill Hospital in New York to his long-standing secretary Joyce Coles on his continuing experience in hospital.
Letter to Renata Gaddini
Authors: Winnicott Donald W.
Published: March 2017

Winnicott’s letter to Renata Gaddini from hospital in New York on the books Winnicott has been reading.
The Use of an Object in the Context of Moses and Monotheism
Authors: Winnicott Donald W.
Published: March 2017

In this paper, Winnicott discusses Freud’s late essay Moses and Monotheism and presents an advancement of Freud’s paper using the conclusions of his own work culminating in the paper ‘The Use of an Object’.
Some Principles of Child Analysis
Authors: Winnicott Donald W.
Published: March 2017

Winnicott’s notes on the principles of child analysis, probably made for teaching purposes. He notes similarities and differences between child and adult work and stages of child development. The characteristics of the analyst and what the child can teach the analyst, as well as the sociological implications of this work, are also discussed.
Letter to Child Care News
Authors: Winnicott Donald W.
Published: March 2017

Letter to the editor of Child Care News on the failure of behaviour therapy.
Additional Note on Psycho-Somatic Disorder
Authors: Winnicott Donald W.
Published: March 2017

In this note, Winnicott recounts the session of a female patient in relation to the clinical picture of the obscure connection of chronic skin conditions to psychotic disorders of the mind. Depersonalization and the skin as the boundary of the self are also discussed.
The Building Up of Trust
Authors: Winnicott Donald W.
Published: March 2017

In this paper, Winnicott discusses the conditions for the building up of trust in very young children. He writes about internal stress inherent in emotional growth and stresses which come from environmental provision such as unreliability and the break up of continuity in the child’s life.
Psychologists as a Group
Authors: Winnicott Donald W.
Published: March 2017

In this discussion, Winnicott admits that he is only partially equipped to talk about psychology due to various antagonisms and prejudices coming from psychology against dynamic psychology and the great number of writings antagonistic to those concerned with the development of the child outside the area of academic psychology. Winnicott is critical of academic psychology but not of psychologists as persons.
Letter to Michael Fordham
Authors: Winnicott Donald W.
Published: March 2017

Letter to Dr Fordham on speaking at a Jungian meeting.
Letter to Renata Gaddini
Authors: Winnicott Donald W.
Published: March 2017

Postcard to Dr Gaddini thanking her for her card.
Two Further Clinical Examples
Authors: Winnicott Donald W.
Published: March 2017

In these clinical examples and the theoretical considerations consequent to them, Winnicott broadens out the subject of personalisation and of psycho-somatic in-dwelling in considering a young woman with a severe disability and a healthy girl who happened to have a dark skin. This chapter includes two case histories and consultations together with their discussion.
Creativity and Its Origins
Authors: Winnicott Donald W.
Published: March 2017

In this paper, Winnicott discusses the origins of creativity, stating that creative apperception more than anything else is what makes the individual feel that life is worth living. He contrasts this with a relationship to external reality that is one of compliance, where the world and its details are recognized only as something to be fitted in with or demanding adaptation. He also approaches creativity from the position of male and female elements, using case material involving dissociation of male and female elements in men and women and discussing pure male and female elements.
Not Less Than Everything
Authors: Winnicott Donald W.
Published: March 2017

Three short autobiographical notes in which Winnicott reflects on his own death and recounts memories of his early childhood at home in Plymouth.
The Day-Dreamer
Authors: Winnicott Donald W.
Published: March 2017

A short story by Winnicott, possibly written in his mid 50s.
Found Objects and Waifs
Authors: Winnicott Donald W.
Published: March 2017

A brief set of notes on lost and idealised objects.
Notes on Play
Authors: Winnicott Donald W.
Published: March 2017

Extensive notes on play, its products, psychopathology and sense of achievement in relation to masturbation, society and adolescence.
The Niffle
Authors: Winnicott Donald W.
Published: March 2017

A case study of a boy who has lost his transitional object, a small woollen toy called the Niffle.
Outline for a Study in the Sociology of Knowledge
Authors: Winnicott Donald W.
Published: March 2017

A short, incomplete note on the relation of psychoanalysis to society and in particular to the British Psychoanalytic Society.
Ditty on Enoch Powell
Authors: Winnicott Donald W.
Published: March 2017

A short ditty on the British politician Enoch Powell.
Introduction to Volume 9
Authors: Jemstedt Arne
Published: March 2017

In the Introduction to Volume 9, covering the period of the end of Winnicott’s life, the themes of creativity, creative living, and the paper ‘The Use of an Object’ are discussed at length, stressing Winnicott’s own creativity and originality as a psychoanalytic thinker. Reference is made to Winnicott’s tolerance of paradox, to everyday creativity, to the infant’s creative illusion and its importance, to his benign omnipotence, to his creation of a ‘subjective’ object, and to the silent inner communications of the self, all in connection with the transitional object and phenomena concept, and finally to the states of ‘being’ and ‘doing’.
Introduction to Volume 10
Authors: Armellini Marco
Published: March 2017

In the Introduction to Volume 10 (Therapeutic Consultations in Child Psychiatry), Winnicott’s collection of child and adolescent consultations in child psychiatry, prepared before his death, is discussed. The consultations represent different ways of communicating about integrative and maturational processes, transitional objects and transitional phenomena, the location of cultural experience, environmental provision, mirroring, object usage and object finding, identifications and, above all, creativity and playing. Reference is made to child psychiatry, to the therapeutic consultation, to the ‘Squiggle Game’, and to the three distinct sections of the collection and their significance.
Case II: ‘Robin’ aet 5 Years
Authors: Winnicott Donald W.
Published: March 2017

This is case II in part 1 of Winnicott’s book Therapeutic Consultations in Child Psychiatry: the case of ‘Robin’, aet 5 years.
Case VIII: ‘Charles’ aet 9 Years
Authors: Winnicott Donald W.
Published: March 2017

This is case VIII in part 2 of Winnicott’s book Therapeutic Consultations in Child Psychiatry: the case of ‘Charles’ aet 9 years.
Case XI: ‘Hesta’ aet 16 Years
Authors: Winnicott Donald W.
Published: March 2017

This is case XI in part 2 of Winnicott’s book Therapeutic Consultations in Child Psychiatry: the case of ‘Hesta’ aet 16 years.
Case XXI: ‘George’ aet 13 Years
Authors: Winnicott Donald W.
Published: March 2017

This is case XXI in part 3 of Winnicott’s book Therapeutic Consultations in Child Psychiatry: the case of ‘George’ aet 13 years.
Preface
Authors: Winnicott Clare
Published: March 2017

Clare Winnicott’s Preface to Winnicott’s posthumously published book Human Nature, in which she outlines the historical background to the collection of notes which make up this work.
Introduction
Authors: Winnicott Donald W.
Published: March 2017

The Introduction to Part I of Human Nature. Winnicott introduces Part I as a look at human nature through the study of the child, using a developmental approach. He chooses to start at the age of four, and work backwards to the beginnings of the individual. He offers a psychoanalytic approach to paediatrics, in particular the emotional health of the child.
Ill-Health
Authors: Winnicott Donald W.
Published: March 2017

In this chapter, Winnicott looks at the interrelationship of body disease, and psychological disorder. He outlines in more detail somatic ill health, including the category of allergies, and then the effect of the psyche on the body and its functioning.
The Psycho-Somatic Field
Authors: Winnicott Donald W.
Published: March 2017

In this paper, Winnicott discusses Freud’s late essay Moses and Monotheism and presents a further development of Freud’s paper using the conclusions of his own work related in the paper ‘The Use of an Object’.
Hypochondriacal Anxiety
Authors: Winnicott Donald W.
Published: March 2017

In this chapter, Winnicott describes the development of ordinary doubt about the self into an extreme form and the struggle to manage the forces of ‘good’ and ‘evil’ within. Psychosomatic illness is the transferring of unmanageable fantasies into bodily states that then become all-controlling. The original fantasy sources of the difficulties then become unavailable for treatment without analytic intervention.
A Primary State of Being: Pre-Primitive Stages
Authors: Winnicott Donald W.
Published: March 2017

In this chapter, Winnicott looks at the earliest stages of emotional development and the fact of dependence of infant upon mother. From a kind of ‘not being’ the baby comes, with sensitive care, into a state of ‘being’. There is a paradox here for Winnicott: the baby is essentially alone and, without knowing it, also extremely dependent on the caring environment mother. Winnicott posits that this ‘aloneness’ is normal and occurs because dependence has not yet been recognised. He considers the place of Freud’s life and death instincts, proposing instead that the aloneness as life begins (and ideas about the ‘second death’ after life ends) arises as a result of a state of unawareness of dependence.
Editor’s Foreword
Authors: Ramzy Ishak
Published: March 2017

The editor of The Piggle, Ishak Ramzy, describes his experience of meeting and working with Winnicott, and describes the history of the clinical notes on the Piggle.
Twelfth Consultation
Authors: Winnicott Donald W.
Published: March 2017

The thirteenth chapter of The Piggle consists of Winnicott’s verbatim report and commentary on the twelfth consultation with Gabrielle, 8 October, 1965, along with three letters from her mother and one from Gabrielle.
Fifteenth Consultation
Authors: Winnicott Donald W.
Published: March 2017

The sixteenth chapter of The Piggle consists of Winnicott’s verbatim report and commentary on the fifteenth consultation with Gabrielle, 3 August, 1966.
Sixteenth Consultation
Authors: Winnicott Donald W.
Published: March 2017

The seventeenth chapter of The Piggle consists of Winnicott’s verbatim report and commentary on the sixteenth and final consultation with Gabrielle, 28 October, 1966, and afterword written by her parents.
Behavioral interventions to improve asthma outcomes: a systematic review of recent publications
Authors: Mosnaim Giselle S. , Akkoyun Esra , Eng Joshua , Shalowitz Madeleine U.
Published: March 2017

Purpose of review

Asthma outcomes are influenced by factors at multiple ecological levels: the individual and his/her family, home, medical care, and community. This systematic review describes recently published single-level and multilevel behavioral interventions to improve asthma outcomes.

Recent findings

Of the 23 total title/abstracts reviewed in the original systematic search of PubMed, Ovid, Scopus, PsychINFO, and CIHAHL reference review databases, six met inclusion criteria. Five of the studies focused on low-income and/or minority populations. Promising interventions include culturally tailored online asthma self-management programs and family-centered asthma education delivered at the bedside during hospitalization for an acute asthma exacerbation.

Culturally, tailored online self-management programs offer difficult-to-reach populations asthma support that can be completed at the time and pace most convenient for the individual user. Family-focused asthma education, delivered at the bedside during an acute asthma hospitalization by highly motivated lay volunteers, is an efficacious and low-cost approach to improving pediatric asthma self-management.
Novel immunotherapy and treatment modality for severe food allergies
Authors: Nagakura Ken-ichi , Sato Sakura , Yanagida Noriyuki , Ebisawa Motohiro
Published: March 2017

Purpose of review

In recent years, many studies on oral immunotherapy (OIT) have been conducted; however, few have focused on severe food allergies. The purpose of this review was to assess the efficacy and safety of oral immunotherapies for patients with severe food allergy.

Recent findings

We reviewed multiple immunotherapy reports published within a few years or reports focusing on severe food allergies. We also investigated recent studies on OIT and novel food allergy management.

Immunotherapies targeting low-dose antigen exposure and oral food challenges using low-dose target volumes may be safer than conventional OIT. It is necessary to consider which immunotherapy regimen is appropriate based on allergy severity of the patient.
Effect of Thoracic Epidural Anesthesia on Ventricular Excitability in a Porcine Model
Authors: Howard-Quijano Kimberly , Takamiya Tatsuo , Dale Erica A. , Yamakawa Kentaro , Zhou Wei , Buckley Una , Mahajan Aman
Published: March 2017

Background

Imbalances in the autonomic nervous system, namely, excessive sympathoexcitation, contribute to ventricular tachyarrhythmias. While thoracic epidural anesthesia clinically suppresses ventricular tachyarrhythmias, its effects on global and regional ventricular electrophysiology and electrical wave stability have not been fully characterized. The authors hypothesized that thoracic epidural anesthesia attenuates myocardial excitability and the proarrhythmic effects of sympathetic hyperactivity.

Methods

Yorkshire pigs (n = 15) had an epidural catheter inserted (T1 to T4) and a 56-electrode sock placed on the heart. Myocardial excitability was measured by activation recovery interval, dispersion of repolarization, and action potential duration restitution at baseline and during programed ventricular extrastimulation or left stellate ganglion stimulation, before and 30 min after thoracic epidural anesthesia (0.25% bupivacaine).

Results

After thoracic epidural anesthesia infusion, there was no change in baseline activation recovery interval or dispersion of repolarization. During programmed ventricular extrastimulation, thoracic epidural anesthesia decreased the maximum slope of ventricular electrical restitution (0.70 ± 0.24 vs. 0.89 ± 0.24; P = 0.021) reflecting improved electrical wave stability. Thoracic epidural anesthesia also reduced myocardial excitability during left stellate ganglion stimulation–induced sympathoexcitation through attenuated shortening of activation recovery interval (−7 ± 4% vs. −4 ± 3%; P = 0.001), suppression of the increase in dispersion of repolarization (313 ± 293% vs. 185 ± 234%; P = 0.029), and reduction in sympathovagal imbalance as measured by heart rate variability.

Conclusions

Our study describes the electrophysiologic mechanisms underlying antiarrhythmic effects of thoracic epidural anesthesia during sympathetic hyperactivity. Thoracic epidural anesthesia attenuates ventricular myocardial excitability and induces electrical wave stability through its effects on activation recovery interval, dispersion of repolarization, and the action potential duration restitution slope.
Breast cancer education for schoolgirls: an exploratory study
Authors: Brown Nicola , Smith Jenny , Brasher Amanda , Omrani Atefeh , Wakefield-Scurr Joanna
Published: March 2017

Adolescent girls are an important target group for breast cancer education and promoting breast awareness. However, research has not established schoolgirls’ perceived importance of breast cancer education or explored factors that may impact engagement. This study aimed to identify schoolgirls’ concerns about breast cancer, desire to know more and perceived importance of breast cancer education, and explored associations with demographic factors. Of 2089 schoolgirls (11–18 years) surveyed, 1958 completed all relevant breast cancer questions and demographic factors (ethnicity, school type, breast size, physical activity level and age). χ
2-Tests assessed associations between demographics, desire to know more and perceived importance of breast cancer. Overall, 44% of schoolgirls reported concerns about breast cancer, 72% wanted to know more and 77% rated the topic as extremely important. Breast size was not associated with wanting to know more about breast cancer. Schoolgirls who wanted to know more about breast cancer were White, from single-sex schools with boys at sixth form, more physically active and older. However, among other ethnic groups, school types and physical activity levels, the proportion of girls who wanted to know more about breast cancer was still high (≥61%). This study provides evidence of the need for breast cancer education for schoolgirls across all school types, irrespective of breast size or physical activity levels. The results highlight the need to be inclusive and engage schoolgirls from all ethnic groups and to promote breast awareness at a young age to ensure effective breast cancer education.
The Effectiveness of Matrix Cauterization With Bichloracetic Acid in the Treatment of Ingrown Toenails
Authors: Terzi Erdinc , Guvenc Ulas , Tursen Belma , Tursen Umit , Kaya Tamer Irfan
Published: March 2017

BACKGROUND

Chemical matricectomy is performed mainly by 2 agents, phenol and sodium hydroxide. Chemical matricectomy with phenol has a low recurrence rate and good cosmetic results, but it produces extensive tissue destruction and can result in drainage and a delayed healing time. These adverse effects have brought forward the use of chemical agents such as sodium hydroxide and trichloroacetic acid for matricectomy.

OBJECTIVE

This prospective study aimed mainly to evaluate the efficacy of partial nail avulsion and selective chemical cauterization of the matrix using 90% bichloracetic acid (BCA) in the treatment of the ingrown nails.

MATERIALS AND METHODS

A total of 30 patients with 58 ingrown toenail edges were included in this study. All of the patients underwent chemical matricectomy with 90% BCA after partial nail avulsion. Adverse effects such as postoperative pain and drainage were minimal in most of the patients.

RESULTS

One patient who underwent matricectomy had recurrence in a single nail edge (1.8%) at the 12th month of the follow-up. No recurrence was observed in 29 patients during mean follow-up period. This was considered to be statistically significant (p < .001).

CONCLUSION

This is the first study to use BCA for the treatment of ingrown toenail. Partial nail avulsion followed by BCA matricectomy is a safe, simple, and effective method with low rates of postoperative morbidity and high rates of success. Therefore, partial nail avulsion and BCA matricectomy can be used as an alternative treatment method for the treatment of ingrown toenails.
Improving Pressure Ulcer Reconstruction: Our Protocol and the COP (Cone of Pressure) Flap
Authors: Gargano Francesco , Edstrom Lee , Szymanski Karen , Schmidt Scott , Bevivino Jack , Zienowicz Richard , Stark Jennifer , Taylor Helena O. , Podda Silvio , Liu Paul
Published: March 2017

Background:

Surgical treatment of pressure ulcers is challenging for high recurrence rates. Deepithelialized flaps have been used previously with the aim to eliminate shearing forces and the cone of pressure (COP) effect. The goal of this study is to adopt a standardized protocol and evaluate if 2 different flap techniques affect outcomes.

Methods:

The novel COP flap is illustrated. Twenty patients were prospectively treated with flap coverage over a 36-month period. According to the flap type, patients were assigned to 2 groups: group 1 with 11 patients treated with the COP flap and group 2 with 9 patients treated with conventional flap without anchoring technique. We adopted a standardized protocol of debridement, tissue cultures, and negative-pressure wound therapy. Rotation fasciocutaneous flaps were used for both groups and mean follow-up was 19 months. The COP flap is a large deepithelialized rotation flap inset with transcutaneous nonabsorbable bolster sutures. The 2 groups were comparable for demographics and ulcer location and size (P < 0.05). Five patients showed positive cultures and were treated with antibiotics and negative-pressure therapy before surgery.

Results:

Recurrence rates were 12% in the COP flap group and 60% in the conventional flap coverage group (P < 0.001). Results were compared at 16-month follow-up.

Conclusions:

The COP flap significantly reduces recurrences and eliminates shearing forces, suture ripping, and tension on superficial soft-tissue layers. The technique can be applied to both ischial and sacral pressure sores. The flap provides padding over bony prominence without jeopardizing flap vascularity.
EARLY DETECTION OF RETINAL HEMANGIOBLASTOMAS IN VON HIPPEL–LINDAU DISEASE USING ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY
Authors: Chen Xuejing , Sanfilippo Christian J. , Nagiel Aaron , Hosseini Hamid , Mitchell Devery , McCannel Colin A. , Schwartz Steven D. , McCannel Tara A.
Published: March 2017

Purpose:

To study the use of ultra-widefield fluorescein angiography (UWF FA) in the detection and management of retinal capillary hemangioblastomas in patients with von Hippel–Lindau disease.

Methods:

This is a retrospective study of patients with von Hippel–Lindau disease who underwent UWF FA using the Optos camera at a single center from June 2009 to May 2015. The clinical use of UWF FA was reviewed, and the number of hemangioblastomas identified on UWF FA was compared with ophthalmoscopy and a simulated seven standard field (7SF) FA montage.

Results:

Twenty eyes of 10 patients were identified. Only 33% of lesions seen on UWF FA were also found on ophthalmoscopy, and 88% of lesions visualized on UWF FA were located outside the 7SF overlay. In 5 eyes that had gaze steering, 18% of lesions could be visualized only on gaze-steered images. For the 14 eyes with data available, 6 had procedures recommended and 8 eyes observed based on data from UWF FA. One of 20 eyes had a lesion on ophthalmoscopy that was missed by imaging.

Conclusion:

Ultra-widefield FA using the Optos camera is helpful for the evaluation and management of patients with von Hippel–Lindau disease. The UWF FA with gaze steering appears to detect more hemangioblastomas than ophthalmoscopy and conventional angiography.
Implementation strategies in pediatric neurocritical care
Authors: Markham Christopher , Proctor Enola K. , Pineda Jose A.
Published: March 2017

Purpose of review

Brain-directed critical care for children is a relatively new area of subspecialization in pediatric critical care. Pediatric neurocritical care teams combine the expertise of neurology, neurosurgery, and critical care medicine. The positive impact of delivering specialized care to pediatric patients with acute neurological illness is becoming more apparent, but the optimum way to implement and sustain the delivery of this is complicated and poorly understood. We aim to provide emerging evidence supporting that effective implementation of pediatric neurocritical care pathways can improve patient survival and outcomes. We also provide an overview of the most effective strategies across the field of implementation science that can facilitate deployment of neurocritical care pathways in the pediatric ICU.

Recent findings

Implementation strategies can broadly be grouped according to six categories: planning, educating, restructuring, financing, managing quality, and attending to the policy context. Using a combination of these strategies in the last decade, several institutions have improved patient morbidity and mortality. Although much work remains to be done, emerging evidence supports that implementation of evidence-based care pathways for critically ill children with two common neurological diagnoses – status epilepticus and traumatic brain injury – improves outcomes.

Pediatric and neonatal neurocritical care programs that support evidence-based care can be effectively structured using appropriately sequenced implementation strategies to improve outcomes across a variety of patient populations and in a variety of healthcare settings.
Orthopaedic Snafus
Authors: Smith Mary Atkinson , Walsh Colleen , Levin Barbara , Eten Kathryn L. , Yager Melissa
Published: March 2017

The potential for adverse events exists when treating and managing orthopaedic patients in the intraoperative or postoperative environments, especially when it comes to falls, surgical site infections, venous thromboembolism, and injuries to nerves and blood vessels. Orthopaedic nurses play a vital role in the promotion and use of evidence-based interventions to decrease the incidence of these adverse events, improve quality of care, and minimize the financial burden related to these adverse events.
The Effects of Postdischarge Telephone Counseling and Short Message Service on the Knee Function, Activities of Daily Living, and Life Satisfaction of Patients Undergoing Total Knee Replacement
Authors: Park Kyung Hye , Song Mi Ryeong
Published: March 2017

BACKGROUND:

No study comparing short message service (SMS) texts and telephone counseling for patients undergoing total knee replacement (TKR) has been reported.

PURPOSE:

The purpose of the study was to provide postdischarge telephone counseling and SMS texts to TKR patients and to analyze the effects of these services on their knee function (KF), activities of daily living (ADL), and life satisfaction (LS).

METHODS:

This study used a randomized clinical trial design. This study was conducted with 40 patients (counseling group: 21; SMS group: 19). In the telephone counseling group and the SMS group, KF, ADL, and LS were assessed before surgery and 1 and 3 months after TKR.

RESULTS:

Telephone counseling and SMS texts have the same effects on KF, ADL, and LS of TKR patients.

CONCLUSION:

Future research is needed to determine optimal frequency and duration of post-TKR SMS to support patients who have undergone TKR.
Acute Myeloid Leukemia (AML): Upregulation of BAALC/MN1/MLLT11/EVI1 Gene Cluster Relate With Poor Overall Survival and a Possible Linkage With Coexpression of MYC/BCL2 Proteins
Authors: Akhter Ariz , Farooq Fahad , Elyamany Ghaleb , Mughal Muhammad K. , Rashid-Kolvear Fariborz , Shabani-Rad Meer-Taher , Street Lesley , Mansoor Adnan
Published: March 2017

Background:

Molecular heterogeneity accounts for the variable and often poor prognosis in acute myeloid leukemia (AML). The current risk stratification strategy in clinical practice is limited to karyotyping and limited molecular studies screening for genetic mutations such as FLT-3 and NPM1. There is opportunity to identify further molecular prognostic markers, which may also lay the groundwork for the development of novel targeted therapies. Complex molecular technologies require transition into widely available laboratory platforms, for better integration into routine clinical practice.

Method:

In a defined subset (MYC
+
/BCL2
+
or MYC
−
/BCL2
−
) of AML patients (n=20), we examined expression signature of several genes (n=12) of established prognostic value in AML. RNA expression and MYC/BCL2 protein pattern was correlated with 3 cytogenetic risk groups and overall survival.

Results:

K-means++ unsupervised clustering defined 2 distinct groups with high and low transcript levels of BAALC/MN1/MLLT11/EVI1/SOCS2 genes (>2.5-fold difference; P<0.001). This mRNA signature trended with higher prevalence of MYC/BCL2 coexpression (P<0.057) and poor overall survival (P<0.036), but did not correlate with conventional cytogenetic risk groups (P<0.084).

Conclusions:

This pilot study provides useful data, which may help further refine the prognostic scheme of AML patients outside conventional cytogenetic risk groups. It also presents some biological rationale for future studies to explore the use of novel agents targeting MYC and/or BCL2 genes in combination with conventional chemotherapy protocols for AML.
Differential Expression of Cytochrome C Oxidase Subunit I Along the Colorectal Adenoma: Carcinoma Progression
Authors: Hewedi Iman H. , Farid Rola M. , Sidhom Karima F. , Salman Manal I. , Mostafa Rabab G.
Published: March 2017

Loss in apoptosis competence often results in augmented genomic instability contributing to carcinogenesis. Cytochrome c oxidase subunit I (CcOI) can help assess apoptosis resistance in paraffin-embedded biopsies. In total, 50 colorectal cases including 10 control cases of colectomy for non-neoplastic condition, 15 cases of adenomatous colorectal polyps, and 25 cases of colorectal carcinoma were investigated in this retrospective study for immunohistochemical expression of CcOI. The staining pattern of CcOI was assessed and indices of aberrant expression were calculated as crypt-restricted loss and overall decreased immunostaining (ODI). ODI calculated in the adenocarcinoma tumor tissue was designated as Tr ODI. The crypt-restricted loss and ODI indices of the aberrant CcOI expression are significantly higher in the adenomatous polyps group (2.5% and 47.54%) and in the non-neoplastic mucosa among adenocarcinoma group (2.78% and 49.1%) when they are compared with the control group (0.55% and 7.32%) (P<0.001). A highly significant correlation was noted between Tr ODI and the tumor grade, the nodal status, and the stage among adenocarcinomas. In conclusion, colonic tumors arise in a field of crypts with aberrations in CcOI expression. This aberration is linked to biologically aggressive tumors. CcOI immunostaining may be applied on mucosal samples from patients with colonic adenomatous polyps and patients with previous cancer colon resection to determine individuals who are in need for frequent colonoscopies and/or chemopreventive strategies. Future follow-up studies are warranted to determine the level of expression predictive of recurrence or progression.
Detection of Loss of Heterozygosity (LOH) Using Circulating Cell-free DNA (cfDNA) by Fluorescence-based Multiplex PCR for Identification of Patients With Prostate Cancer
Authors: Seyedolmohadessin S-Maryam , Akbari Mohammad T. , Nourmohammadi Zahra , Basiri Abbas , Pourmand Gholamreza
Published: March 2017

Several lines of evidence suggest that loss of heterozygosity (LOH) in specific chromosomal regions is a common mechanism for the inactivation of tumor-suppressor genes that are implicated in the pathogenesis of prostate cancer (PCa). Short tandem repeat (STR) sequences are extremely reliable genetic markers for the detection of LOH associated with cancers. Hence, in the current study, we investigated the detection of LOH at 6 STR markers (D8S360, D9S1748, D9S171, D8S137, D6S1631, and THRB) using blood circulating cell-free DNA (cfDNA), which can be used to distinguish PCa from benign prostatic hyperplasia (BPH). A total of 136 individuals were included in the study, 76 male patients diagnosed with PCa (50 male patients with localized PCa and 26 male patients with metastatic PCa) as experimental subjects and 60 male patients with BPH as controls. Circulating cfDNA was extracted from plasma samples and amplified with fluorescence-labeled primers specific for known STR markers. We also evaluated the serum prostate-specific antigen in both groups. Our findings revealed that the frequency of LOH at D8S360, D9S1748, D9S171, D8S137, and D6S1631 was significantly higher in PCa subjects than in controls (P<0.05). Of the 6 STR markers, LOH at D8S360 could discriminate metastatic PCa from localized PCa. We found that 71.05% of patients with PCa and 1.66% of BPH subjects had LOH at least at 3 of the markers in cfDNA. Our findings provide additional evidence to support the hypothesis that analysis of LOH at D8S360, D9S1748, D9S171, D8S137, and D6S1631 STR markers using cfDNA can be applied as a noninvasive diagnostic approach for the detection of PCa.
Cellular Interplay and Cytokine Hierarchy Cause Pathological Cardiac Hypertrophy inRAF1-Mutant Noonan Syndrome
Authors: Yin Jiani C. , Platt Mathew J. , Tian Xixi , Wu Xue , Backx Peter H. , Simpson Jeremy A. , Araki Toshiyuki , Neel Benjamin G.
Published: March 2017

Noonan syndrome (NS) is caused by mutations in RAS/ERK pathway genes, and is characterized by craniofacial, growth, cognitive and cardiac defects. NS patients with kinase-activatingRAF1alleles typically develop pathological left ventricular hypertrophy (LVH), which is reproduced inRaf1L613V/+knock-in mice. Here, using inducibleRaf1L613Vexpression, we show that LVH results from the interplay of cardiac cell types. CardiomyocyteRaf1L613Venhances Ca2+sensitivity and cardiac contractility without causing hypertrophy.Raf1L613Vexpression in cardiomyocytes or activated fibroblasts exacerbates pressure overload-evoked fibrosis. Endothelial/endocardial (EC)Raf1L613Vcauses cardiac hypertrophy without affecting contractility. Co-culture and neutralizing antibody experiments reveal a cytokine (TNF/IL6) hierarchy inRaf1L613V-expressingECs that drives cardiomyocyte hypertrophyin vitro. Furthermore, post-natal TNF inhibition normalizes the increased wall thickness and cardiomyocyte hypertrophyin vivo. We conclude that NS cardiomyopathy involves cardiomyocytes, ECs, and fibroblasts, TNF/IL6 signaling components represent potential therapeutic targets, and abnormal EC signaling might contribute to other forms of LVH.
TheToxoplasmacentrocone houses cell cycle regulatory factors
Authors: Naumov Anatoli , Kratzer Stella , Ting Li-Min , Kim Kami , Suvorova Elena S. , White Michael W.
Published: March 2017

Our knowledge of cell cycle regulatory mechanisms in apicomplexan parasites is very limited. In this study, we describe a novelToxoplasma gondiifactor, essential for chromosome replication 1 (ECR1), that has a vital role in chromosome replication and the regulation of cytoplasmic and nuclear mitotic structures. ECR1 was discovered by complementation of a temperature sensitive (ts) mutant that suffers lethal, uncontrolled chromosome replication at 40°C similar to a ts-mutant carrying a defect in topoisomerase. ECR1 is a 52kDa protein containing divergent RING and TRAF-Sina like zinc-binding domains that is dynamically expressed in the tachyzoite cell cycle. ECR1 first appears in the centrocone compartment of the nuclear envelope in early S phase and then in the nucleus in late S phase where it reaches maximum expression. Following nuclear division, but before daughters resolve from the mother, ECR1 is down regulated and is absent in new daughter parasites. The proteomics of ECR1 identified interactions with the ubiquitin-mediated protein degradation machinery and the minichromosome maintenance complex and the loss of ECR1 led to increased stability of a key member of this complex, MCM2. ECR1 also forms a stable complex with the CDK-related kinase, TgCrk5, which shares a similar cell cycle expression and localization during tachyzoite replication. Altogether, the results of this study suggest ECR1 may be a unique E3 ligase that regulates DNA licensing and other mitotic processes. Importantly, the localization of ECR1/TgCrk5 in the centrocone indicates this Apicomplexa-specific spindle compartment houses important regulatory factors that control the parasite cell cycle.

IMPORTANCE

Parasites of the apicomplexan family are important causes of human disease including malaria, toxoplasmosis, and cryptosporidiosis. Parasite growth is the underlying cause of pathogenesis, yet despite this importance the molecular basis for parasite replication is poorly understood. Filling this knowledge gap cannot be accomplished by mining recent whole genome sequencing because apicomplexan cell cycles differ substantially and lack many of the key regulatory factors of well-studied yeast and mammalian cell division models. We have utilized forward genetics to discover essential factors that regulate cell division in these parasites using theToxoplasma gondiimodel. An example of this approach is described here with the discovery of a putative E3 ligase/protein kinase mechanism involved in regulating chromosome replication and mitotic processes of asexual stage parasites.
Horizontal Gene Transfer of Functional Type VI Killing Genes by Natural Transformation
Authors: Thomas Jacob , Watve Samit S. , Ratcliff William C. , Hammer Brian K.
Published: March 2017

Horizontal gene transfer can have profound effects on bacterial evolution by allowing individuals to rapidly acquire adaptive traits that shape their strategies for competition. One strategy for intermicrobial antagonism often used by Proteobacteria is the genetically-encoded contact-dependent Type VI secretion system (T6SS); a weapon used to kill heteroclonal neighbors by direct injection of toxic effectors. Here, we experimentally demonstrate thatVibrio choleraecan acquire new T6SS effector genes via horizontal transfer and utilize them to kill neighboring cells. Replacement of one or more parental alleles with novel effectors allows the recombinant strain to dramatically outcompete its parent. Through spatially-explicit simulation modeling, we show that the HGT is risky: transformation brings a cell into conflict with its former clonemates, but can be adaptive when superior T6SS alleles are acquired. More generally, we find that these costs and benefits are not symmetric, and that high rates of HGT can act as hedge against competitors with unpredictable T6SS efficacy. We conclude that antagonism and horizontal transfer drive successive rounds of weapons-optimization and selective sweeps, dynamically shaping the composition of microbial communities.
Crystal structures of three 4-substituted-2,2′-bipyridines synthesized by Sonogashira and Suzuki–Miyaura cross-coupling reactions
Authors: Luong Thi Thu Thuy , Nguyen Bich Ngan , Nguyen Hien , Van Meervelt Luc
Published: March 2017

Facile synthetic routes for three 4-substituted 2,2′-bipyridine derivatives, 4-[2-(4-methylphenyl)ethynyl]-2,2′-bipyridine, C19H14N2, (I), 4-[2-(pyridin-3-yl)ethynyl]-2,2′-bipyridine, C17H11N3, (II), and 4-(indol-4-yl)-2,2′-bipyridine, C18H13N3, (III),viaSonogashira and Suzuki–Miyaura cross-coupling reactions, respectively, are described. As indicated by X-ray analysis, the 2,2′-bipyridine core, the ethylene linkage and the substituents of (I) and (II) are almost planar [dihedral angles between the two ring systems: 8.98 (5) and 9.90 (6)° for the two molecules of (I) in the asymmetric unit and 2.66 (14)° for (II)], allowing π-conjugation. On the contrary, in (III), the indole substituent ring is rotated significantly out of the bipyridine plane [dihedral angle = 55.82 (3)°], due to steric hindrance. The crystal packings of (I) and (II) are dominated by π–π interactions, resulting in layers of molecules parallel to (30-2) in (I) and columns of molecules along theaaxis in (II). The packing of (III) exhibits zigzag chains of molecules along thecaxis interacting through N—H...N hydrogen bonds and π–π interactions. The contributions of unknown disordered solvent molecules to the diffraction intensities in (II) were removed with the SQUEEZE [Spek (2015).Acta Cryst.C71, 9–18] algorithm ofPLATON. The given chemical formula and other crystal data do not take into account these solvent molecules.
Crystal structure of bis(4-benzoylpyridine-κN)bis(methanol-κO)bis(thiocyanato-κN)cobalt(II)
Authors: Suckert Stefan , Werner Julia , Jess Inke , Näther Christian
Published: March 2017

The crystal structure of the title compound, [Co(NCS)2(C12H9NO)2(CH3OH)2], consists of cobalt(II) cations that are octahedrally coordinated by two N-terminal bonding thiocyanato anions, two methanol molecules and two 4-benzoylpyridine ligands into discrete complexes that are located on centres of inversion. These complexes are further linked by O—H...O hydrogen bonding between the hydroxy H atom of the methanol ligand and the carbonyl O atom of the 4-benzoylpyridine ligand of a neighboring complex into layers parallel to (101). No pronounced intermolecular interactions are observed between these layers.
Crystal structure and Hirshfeld surface analysis of 1-(4-bromophenyl)-2-{[5-(pyridin-3-yl)-1,3,4-oxadiazol-2-yl]sulfanyl}ethan-1-one
Authors: Bano Huma , Hussain Shafqat , Khan Khalid M. , Perveen Shahnaz , Yousuf Sammer
Published: March 2017

In the title compound, C15H10BrN3O2S, the dihedral angles between the 1,3,4-oxadiazole ring and the 3-pyridinyl and bromobenzene rings are 12.17 (15) and 18.74 (15)°, respectively. In the crystal, the molecules are linked into [100] chains by way of C—H...O, C—H...N, C—H...S hydrogen bonds. The Hirshfeld surface analysis indicates that the most important contributions to the packing are H...H (19.5%), N...H (17.3%), C...H (15.5%), Br...H (11.7%), and O...H (11.0%) interactions.
Data mining of iron(II) and iron(III) bond-valence parameters, and their relevance for macromolecular crystallography
Authors: Zheng Heping , Langner Karol M. , Shields Gregory P. , Hou Jing , Kowiel Marcin , Allen Frank H. , Murshudov Garib , Minor Wladek
Published: March 2017

The bond-valence model is a reliable way to validate assumed oxidation states based on structural data. It has successfully been employed for analyzing metal-binding sites in macromolecule structures. However, inconsistent results for heme-based structures suggest that some widely used bond-valenceR0parameters may need to be adjusted in certain cases. Given the large number of experimental crystal structures gathered since these initial parameters were determined and the similarity of binding sites in organic compounds and macromolecules, the Cambridge Structural Database (CSD) is a valuable resource for refining metal–organic bond-valence parameters.R0bond-valence parameters for iron(II), iron(III) and other metals have been optimized based on an automated processing of all CSD crystal structures. Almost allR0bond-valence parameters were reproduced, except for iron–nitrogen bonds, for which distinctR0parameters were defined for two observed subpopulations, corresponding to low-spin and high-spin states, of iron in both oxidation states. The significance of this data-driven method for parameter discovery, and how the spin state affects the interpretation of heme-containing proteins and iron-binding sites in macromolecular structures, are discussed.
Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site
Authors: Pidugu Lakshmi Swarna Mukhi , Neu Heather , Wong Tin Lok , Pozharski Edwin , Molloy John L. , Michel Sarah L. J. , Toth Eric A.
Published: March 2017

3-Hydroxyanthranilate 3,4-dioxygenase (3HAO) is an enzyme in the microglial branch of the kynurenine pathway of tryptophan degradation. 3HAO is a non-heme iron-containing, ring-cleaving extradiol dioxygenase that catalyzes the addition of both atoms of O2to the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3-HANA) to form quinolinic acid (QUIN). QUIN is a highly potent excitotoxin that has been implicated in a number of neurodegenerative conditions, making 3HAO a target for pharmacological downregulation. Here, the first crystal structure of human 3HAO with the native iron bound in its active site is presented, together with an additional structure with zinc (a known inhibitor of human 3HAO) bound in the active site. The metal-binding environment is examined both structurally andviainductively coupled plasma mass spectrometry (ICP-MS), X-ray fluorescence spectroscopy (XRF) and electron paramagnetic resonance spectroscopy (EPR). The studies identified Met35 as the source of potential new interactions with substrates and inhibitors, which may prove useful in future therapeutic efforts.
Is dimerization a common feature in thioredoxins? The case of thioredoxin fromLitopenaeus vannamei
Authors: Campos-Acevedo Adam A. , Sotelo-Mundo Rogerio R. , Pérez Javier , Rudiño-Piñera Enrique
Published: March 2017

The quaternary structure of the redox protein thioredoxin (Trx) has been debated. For bacterial Trx, there is no question regarding its monomeric state. In humans and other eukaryotes, the presence of a cysteine residue at the crystallographic symmetry axis points to the relevance of dimer formation in solution andin vivo. Crystallographic data for shrimp thioredoxin (LvTrx) obtained under different redox conditions reveal a dimeric arrangement mediated by a disulfide bond through residue Cys73 and other hydrophobic interactions located in the crystallographic interface, as reported for human Trx. Through the analysis of five mutants located at the crystallographic interface, this study provides structural and biochemical evidence for the existence in solution of monomeric and dimeric populations of wild-typeLvTrx and five mutants. Based on the results of biochemical assays, SAXS studies and the crystallographic structures of three of the studied mutants (Cys73Ser, Asp60Ser and Trp31Ala), it is clear that the Cys73 residue is essential for dimerization. However, its mutation to Ser produces an enzyme which has similar redox activityin vitroto the wild type. A putative regulatory function of dimerization is proposed based on structural analysis. Nonetheless, the biological role ofLvTrx dimerization needs to be experimentally unveiled. Additionally, the findings of this work reopen the discussion regarding the existence of similar behaviour in human thioredoxin, which shares a Cys at position 73 withLvTrx, a structural feature that is also present in some Trxs from vertebrates and crustaceans.