bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical activity volume, intensity, and incident cardiovascular disease
Authors: Dempsey Paddy C , Rowlands Alex V , Strain Tessa , Zaccardi Francesco , Dawkins Nathan , Razieh Cameron , Davies Melanie J , Khunti Kamlesh K , Edwardson Charlotte L , Wijndaele Katrien , Brage Soren , Yates Tom
Published: October 2022

Aims

The interplay between physical activity (PA) volume and intensity is poorly understood in relation to cardiovascular disease (CVD) risk. This study aimed to investigate the role of PA intensity, over and above volume, in relation to incident CVD.

Methods and results

Data were from 88 412 UK Biobank middle-aged adults (58% women) without prevalent CVD who wore accelerometers on their dominant wrist for 7 days, from which we estimated total PA energy expenditure (PAEE) using population-specific validation. Cox proportional hazards regressions modelled associations between PAEE (kJ/kg/day) and PA intensity (%MVPA; the fraction of PAEE accumulated from moderate-to-vigorous-intensity PA) with incident CVD (ischaemic heart disease or cerebrovascular disease), adjusted for potential confounders. There were 4068 CVD events during 584 568 person-years of follow-up (median 6.8 years). Higher PAEE and higher %MVPA (adjusted for PAEE) were associated with lower rates of incident CVD. In interaction analyses, CVD rates were 14% (95% confidence interval: 5–23%) lower when MVPA accounted for 20% rather than 10% of 15 kJ/kg/d PAEE; equivalent to converting a 14 min stroll into a brisk 7 min walk. CVD rates did not differ significantly between values of PAEE when the %MVPA was fixed at 10%. However, the lowest CVD rates were observed for combinations of both higher PAEE and %MVPA.

Conclusion

Reductions in CVD risk may be achievable through higher PA volume and intensity, with the role of moderately intense PA appearing particularly important. This supports multiple approaches or strategies to PA participation, some of which may be more practical or appealing to different individuals.
Activating the ‘peerness’ of youth leaders in a community sports programme throughtechneandphronesis
Authors: Christensen Julie H , Evans Adam B , Klinker Charlotte D , Staal Marie T , Bentsen Peter , Nielsen Glen
Published: October 2022

Peer-to-peer approaches engage groups of people considered to share one or more characteristics that identify them as peers and draw on rationales of credibility, identification and role modelling in peer-to-peer interactions. Despite the popularity of the approach, the ways in which the peer leadership component specifically contributes to health promotion is not thoroughly understood. We suggest that a first step for making use of peer leader characteristics is to make explicit what the peer leadership component is expected to bring to a programme. To approach such an understanding, we investigated how peer leaders can be supported in activating their ‘peerness’ in health promotion programmes, using as a case the peer leader education of a youth-led, peer-to-peer community sports programme, implemented by the non-profit street sports organization, GAME. We analysed the peer leader training programme’s learning objectives and field notes from observations of the training programme. The empirical material was analysed using an abductive approach by drawing upon contemporary interpretations of two forms of knowledge originally proposed by Aristotle. In so doing, this article explores how the development of techne (practical knowledge) and phronesis (practical wisdom) was supported in a peer leader training programme for young people. Findings suggest that supporting the development of both these types of knowledge can strengthen programme planners’ attention to the contribution of peers. Concurrently, an emphasis on promoting phronesis in peer leader training can support and encourage peer leaders in activating their ‘peerness’ in peer-to-peer health promotion programmes.
‘Sheds for Life’: delivering a gender-transformative approach to health promotion in Men’s Sheds
Authors: McGrath Aisling , Murphy Niamh , Richardson Noel
Published: October 2022

Research has highlighted the importance of gendered approaches to engage men with health. Sheds for Life (SFL) is a health and wellbeing initiative that utilizes evidence-based and gender-specific approaches to engage hard to reach men with health promotion directly in the Men’s Sheds (Sheds) setting. To understand the impact of SFL and how participants (Shedders) experienced SFL in practice, this qualitative study applied a framework of constructivism and aimed to explore how gendered approaches impacted engagement with SFL through Shedder’s own accounts of their attitudes, opinions and experiences. Qualitative methods incorporating ethnographical observations, focus groups (n = 8) and short semi-structured interviews (n = 19) were conducted with SFL participants in the Shed setting. Reflexive thematic analysis was used to analyse the data to faithfully capture Shedders’ experiences while acknowledging the reflexive influence of the researcher. Findings led to three key themes: Creating the ‘right environment’; Normalizing meaningful conversations; a legacy for ‘talking health’ with subthemes of creating safety and trust and strengthening of bonds; and transforming perceptions of how men ‘do health’ with subthemes of reaping the benefits of engaging with health and reframing attitudes towards health. This is first study to capture Shedders’ experiences of a structured health promotion initiative in the Shed setting. Findings highlight the value in utilizing the Shed setting to engage men with health and the importance of gender-specific strategies which encourage a gender-transformative approach to men’s health promotion.
Genistein improves renal disease in a mouse model of nephropathic cystinosis: a comparison study with cysteamine
Authors: De Leo Ester , Taranta Anna , Raso Roberto , Polishchuk Elena , D’Oria Valentina , Pezzullo Marco , Goffredo Bianca Maria , Cairoli Sara , Bellomo Francesco , Battafarano Giulia , Camassei Francesca Diomedi , Del Fattore Andrea , Polishchuk Roman , Emma Francesco , Rega Laura Rita
Published: October 2022

Cysteamine is currently the only therapy for nephropathic cystinosis. It significantly improves life expectancy and delays progression to end-stage kidney disease; however, it cannot prevent it. Unfortunately, compliance to therapy is often weak, particularly during adolescence. Therefore, finding better treatments is a priority in the field of cystinosis. Previously, we found that genistein, an isoflavone particularly enriched in soy, can revert part of the cystinotic cellular phenotype that is not sensitive to cysteamine in vitro. To test the effects of genistein in vivo, we fed 2-month-old wild-type and Ctns−/− female mice with either a control diet, a genistein-containing diet or a cysteamine-containing diet for 14 months. Genistein (160 mg/kg/day) did not affect the growth of the mice or hepatic functionality. Compared with untreated mice at 16 months, Ctns−/− mice fed with genistein had lower cystine concentrations in their kidneys, reduced formation of cystine crystals, a smaller number of LAMP1-positive structures and an overall better-preserved parenchymal architecture. Cysteamine (400 mg/kg/day) was efficient in reverting the lysosomal phenotype and in preventing the development of renal lesions. These preclinical data indicate that genistein ameliorates kidney injury resulting from cystinosis with no side effects. Genistein therapy represents a potential treatment to improve the outcome for patients with cystinosis.
Challenges in avoiding deep-water shark bycatch in Azorean hook-and-line fisheries
Authors: Fauconnet Laurence , Catarino Diana , Das Diya , Giacomello Eva , Gonzalez-Irusta José Manuel , Afonso Pedro , Morato Telmo
Published: October 2022

Deep-water sharks are highly diverse, vulnerable, and understudied as a group, despite the increasing pressures on their populations. Twenty-five species of deep-water sharks have been recorded in the Azores, an oceanic archipelago in the mid-North Atlantic, that are regularly caught as bycatch in hook-and-line fisheries. Avoiding the bycatch of deep-water sharks presents multiple challenges due to their high catchability, difficulties in correctly identifying species, and the general lack of data on these species. This review summarizes the findings of recent studies from the region, providing an up-to-date science-based framework for mitigating bycatch effects of Azorean hook-and-line fisheries. Several depth-based, area-based, and gear-based measures have been studied that demonstrate the potential to either avoid or increase the survival of deep-water shark bycatch. However, these measures may have limited efficacy for some species (e.g. highly mobile species) and thus, limited widespread applicability. Convincing fishers to avoid deep-water shark bycatch is also a challenge given the antagonistic interactions with sharks damaging the catch and fishing gear, while simultaneously a market incentive for shark liver oil remains. It highlights the need to proactively engage fishers and incentivize the mitigation of bycatch of deep-water sharks in Azorean waters.
Risks and adaptation options for the Mediterranean fisheries in the face of multiple climate change drivers and impacts
Authors: Hidalgo M , El-Haweet A E , Tsikliras A C , Tirasin E M , Fortibuoni T , Ronchi F , Lauria V , Ben Abdallah O , Arneri E , Ceriola L , Milone N , Lelli S , Hernández P , Bernal M , Vasconcellos M
Published: October 2022

The Mediterranean Sea is among the most vulnerable semi-enclosed seas to climate change. Multiple oceanic changes occur besides warming that can generate numerous ecological, social, and economic risks, challenging fisheries management at various spatial scales—from local to international. In this study, we applied a semi-quantitative climate risk assessment (CRA) to the Mediterranean small pelagic and demersal fisheries in relation to a diversity of climate-related drivers and impacts. We assessed the risks of climate change effects on demersal and small pelagic fisheries resources, fishing operations, livelihoods, and wider social and economic implications in seven sub-regions of the Mediterranean Sea. Ocean warming, an increase in extreme weather events, and changes in vertical stratification resulted in the most important climate drivers. Overall, climate drivers present higher risks to fishing resources and livelihoods than to fishing operations and wider social and economic impacts. The study puts into evidence geographic differences in terms of the drivers and impacts, with the south-eastern Mediterranean being the sub-region with higher risk levels for both fisheries, while the north-central Mediterranean also showed important risk levels for the demersal fisheries. The study furthermore discusses the most plausible adaptive measures in management, policy, research, and livelihoods to be potentially applied to address high priority risks, as well as various implementation concerns and technical effectiveness issues. Enhancing adaptive fisheries management needs to be the primary strategy for this region to reverse the high number of overfished stocks and build resilience to climate change.
A qualitative study exploring challenges and solutions to negotiating goals of care at the end of life in hospital settings
Authors: Devery Kim , Winsall Megan , Rawlings Deb
Published: October 2022

Background

Negotiating goals of care (GoC) with patients is an essential skill for all health-care professionals (HCPs) in hospitals. End-of-Life Essentials (EOLE) is a Commonwealth-funded project that delivers free, peer-reviewed, evidence-based, online education and practice change resources. To date, around 26 000 doctors, nurses and allied health professionals have registered to access the education. ‘Planning End-of-Life Care—Goals of Care’ features in the suite of EOLE modules and includes education around negotiating GoC with patients and families.

Objective

The aim of the study was to explore the views of module learners (HCPs) on challenges they have faced when negotiating GoC at the EOL with patients and families.

Methods

Participants were learners (HCPs) who registered to the EOLE website and engaged with the GoC module. Learners’ responses to the question posed at the end of the module ‘What are the hardest or most challenging things about negotiating GoC with patients and families?’ were extracted for a 12-month period. Qualitative data were analysed thematically in NVivo V.12, guided by the theoretical framework of pragmatism. An open, inductive approach was used to code the data, with axial coding used to refine and organize themes and subthemes.

Results

A total of 451 learner statements were analysed. Five themes emerged from the data: (i) differing views and opinions; (ii) challenges to understanding; (iii) managing emotions; (iv) initiating the EOL conversation and (v) lack of professional knowledge or capacity. Five subthemes were also organized under the theme ‘differing views and opinions’.

Conclusion

Planning EOL care demands high-level, compassionately skilful and sensitive care and services, which are in line with the patient’s and family’s wishes. In practice, however, there are many challenges to this, such as ensuring that patients, families, and HCPs are aware of different expectations regarding future health-care possibilities, and that HCPs are prepared for negotiating GoC to achieve quality and safe EOL care in hospitals.
Entomopathogenic Fungi, Isolated From Soils andBemisia tabaci(Hemiptera: Aleyrodidae) Adults, to Manage theEucalyptusRed Gum Lerp PsyllidGlycaspis brimblecombei(Hemiptera: Aphalaridae)
Authors: Domingues Maurício Magalhães , dos Santos Paula Leite , Gêa Bianca Cristina Costa , de Carvalho Vanessa Rafaela , de Oliveira Fabricio Naka , Soliman Everton Pires , Serrão José Eduardo , Zanuncio José Cola , Zanetti Ronald , Wilcken Carlos Frederico
Published: October 2022

The parasitoid Psyllaephagus bliteus Riek (Hymenoptera: Encyrtidae), entomopathogenic fungi, and chemical insecticides are the main strategies to manage the eucalypts pest Glycaspis brimblecombei Moore. The objective of this study was to isolate and to identify entomopathogenic fungi, collected from Bemisia tabaci Gennadius adults in soybean and tomato crops, and from soil samples in eucalypts, soybean, and native forest areas to evaluate their potential to manage G. brimblecombei. Twelve Beauveria and Cordyceps isolates were selected and compared with the commercial products Boveril Beauveria bassiana Bals. (Hypocreales: Cordycipitaceae), Metarril Metarhizium anisopliae Metschn. (Hypocreales: Clavicipitaceae), and Octane Cordyceps fumosorosea Wize (Hypocreales: Cordycipitaceae) and their respective strains. The fungal isolates were diluted in 0.1% aqueous Tween 80 at a concentration of 1.0 × 108 conidia/ml and sprayed on the G. brimblecombei nymphs with or without lerps. Pest mortality was higher and the TL50 and TL90 lower with the isolates LCBPF 11 C. javanica Frieder. & Bally (Hypocreales: Cordycipitaceae), LCBPF 12 (C. fumosorosea), and LCBPF 67 (C. fumosorosea) from B. tabaci adults. Fungi of the genera Beauveria and Cordyceps developed and caused high mortality of G. brimblecombei nymphs with lerps. The B. bassiana, C. cateniannulata Liang (Hypocreales: Cordycipitaceae), C. fumosorosea, C. javanica, and M. anisopliae isolates showed potential to manage G. brimblecombei. The lerp of this insect enhances entomopathogenic fungus development as a source of inoculum accelerating G. brimblecombei nymph mortality. Entomopathogenic fungi isolated from insects and soils are effective against G. brimblecombei and the presence of the lerp of this insect increases the effectiveness of its control.
Adjuvant nivolumab versus placebo following radical surgery for high-risk muscle-invasive urothelial carcinoma: a subgroup analysis of Japanese patients enrolled in the phase 3 CheckMate 274 trial
Authors: Tomita Yoshihiko , Kobayashi Ko , Kimura Go , Oya Mototsugu , Uemura Hirotsugu , Nishiyama Hiroyuki , Galsky Matthew D , Nasroulah Federico , Collette Sandra , Broughton Edward , Ünsal-Kaçmaz Keziban , Kamisuki Yukinori , Bajorin Dean F
Published: October 2022

Background

The phase 3 CheckMate 274 trial demonstrated superiority of adjuvant nivolumab over placebo after radical surgery in patients with high-risk muscle-invasive urothelial carcinoma. However, the efficacy and safety of adjuvant nivolumab in Japanese patients with muscle-invasive urothelial carcinoma have not been clarified.

Methods

Patients with muscle-invasive urothelial carcinoma were randomized to adjuvant nivolumab 240 mg or placebo (every 2 weeks via intravenous infusion) up to 120 days after radical surgery in CheckMate 274.

Results

Of 49 patients in the Japanese subgroup, 27 and 22 patients were randomized to nivolumab and placebo, respectively. Eleven and 8 patients, respectively, had tumor PD-L1 expression level of 1% or more. The median disease-free survival times in the nivolumab and placebo groups were 29.67 months (95% confidence interval 7.79–not reached) and 9.72 months (95% confidence interval 4.73–not reached), respectively (hazard ratio 0.77, 95% confidence interval 0.35–1.69). The corresponding values in patients with tumor PD-L1 expression level of 1% or more were 29.67 months (95% confidence interval 2.63–not reached) and 25.95 months (95% confidence interval 5.59–not reached) (hazard ratio 1.10, 95% confidence interval 0.31–3.92), respectively. Treatment-related adverse events of Grade 3–4 occurred in 25.9 and 13.6% of patients in the nivolumab and placebo groups, respectively. The most common treatment-related adverse events in the nivolumab group were lipase increased, amylase increased and diarrhea. The changes in quality of life scores from baseline over time were similar in both groups.

Conclusions

The efficacy and safety results in the Japanese subgroup were consistent with the overall population of CheckMate 274.
Cultural Competency in Psychological Assessment
Authors: Mercado Alfonso , Venta Amanda
Published: October 2022

The Latinx population has experienced fast growth and is highly diverse, so access to linguistically and culturally relevant services is crucial yet extremely limited. This book highlights cultural competency in psychological assessment with a focus on working effectively with Latinx groups in mental health settings. It features a hybrid approach benefiting advanced graduate students in psychology, psychiatry residents, and current mental health practitioners. An emphasis on the diversity of Latinx groups—including culturally relevant concepts, cultural clinical interviewing, appropriate psychological assessments, and clinical implications for working with Latinx clients—is presented. The unique role of psychologists and mental health practitioners working effectively with Latinx groups in clinical, research, and advocacy settings is discussed throughout the book.
Psychometric Issues in Assessment with Latinx Persons
Authors: Mercado Alfonso , Venta Amanda
Published: October 2022

An overview of the psychometric issues in assessment with Latinx persons is introduced in this chapter. In addition, the effects of language and culture on psychological assessment are discussed, and the culture language interpretive matrix is introduced. The authors discuss the importance of cross-cultural psychometrics.
Basic considerations in abdominal trauma
Authors: Jhunjhunwala Rashi , Raykar Nakul , Ramos Juan Pablo , Puyana Juan Carlos , Kumar Vineet
Published: October 2022

Falls, workplace accidents, motor vehicle collisions with other vehicles, pedestrians, or stationary objects, physical assault, and interpersonal violence all result in injuries that may require evaluation and management by a trauma team. The optimal care of a patient with blunt or penetrating trauma includes a rapid but comprehensive initial assessment, prompt resuscitation, adjunct imaging, and decision-making on the need for intensive care or operative resources. This chapter provides an overview on abdominal trauma, from the initial evaluation and resuscitation, common patterns of injury, diagnostic testing, operative and non-operative management, and post-operative care. Trauma is not isolated to any particular part of the world, and resources vary. The management of injury must adapt to these variations. Where relevant, the chapter highlights these differences from the perspectives of the authors, trauma surgeons working in very different health systems, spanning three continents.
Retroperitoneal haematoma and injury
Authors: Navsaria Pradeep , Jonas Eduard , Nicol Andrew , Edu Sorin
Published: October 2022

The retroperitoneal space is a wide area lying posterior to the peritoneal cavity and contains a number of visceral (gastrointestinal and genitourinary), vascular, musculoskeletal, and nervous system structures, either wholly or partially. A simple location-based classification of traumatic retroperitoneal haematoma is as follows: central (Zone I), flank or peri-renal (Zone II), and pelvic (Zone III). The commonest Zone 1 aetiologies include injuries to the abdominal aorta and inferior vena cava, the coeliac axis, superior mesenteric artery, and proximal renal vasculature. A Zone II haematoma may result from injuries to the ascending or descending colon, duodenum, kidney, genito-urinary vascular structures, ureters, and muscular vessels. A Zone III haematoma is located in the pelvis which contains the rectum, the bladder, female genitalia, iliac vessels, and their tributaries. In general, all penetrating retroperitoneal haematomas must be explored. Blunt extraperitoneal haematomas are explored in Zone 1, explored in zone II if expanding, and in Zone III packed extra-peritoneally if expanding with post-packing angiography. An exception is a pre-operative CT scan that accurately grades a renal injury that can be managed expectantly. While it is beyond the scope of this chapter to describe the management of retroperitoneal vascular and blunt pelvic trauma; the focus will be on the management of kidney, ureter, pancreas, duodenum, and rectal injuries, which are managed according to their organ injury severity or anatomical location.
Acute abdomen
Authors: Tiwari Ankur V. , Haribhakti Sanjiv
Published: October 2022

Acute abdomen (AA) is one of the most common conditions presenting in the emergency room (ER). There are several causes for AA, the most common being non-specific abdominal pain. These causes are related to the age of patients and the region of abdomen. The incidence of diseases causing such a condition are described in this chapter. A detailed history and thorough clinical examination are important in understanding the probable pathology of disease. Based on this information, the nature of the emergency is understood and treatment instituted. The use of different radiological modalities is vital in arriving at a diagnosis. There are rare causes of AA which, if they elude a diagnosis, makes it difficult to treat the patient. Several of these causes may not need surgical intervention and it is important for a clinician to suspect their presence and rule these out. Prompt management of underlying disease is desirable. A liberal approach towards investigation is advisable when considering inpatient management of patients presenting in the ER.
Neoplasms of the abdominal wall
Authors: Winder Alec Anthony , Davies Emma , Bagué Sílvia , Hayes Andrew
Published: October 2022

Abdominal wall tumours are rare and account for less than 10 per cent of all soft tissue tumours. They comprise a wide range of pathologies with varied clinical behaviours and differing responses to treatment. Therefore, it is necessary to have made a diagnosis of the abdominal wall neoplasm prior to instituting treatment. The two most common neoplasms affecting the muscles of the abdominal wall are desmoid-type fibromatosis and soft tissue sarcoma. This chapter discusses the imaging modalities and biopsy techniques used in securing a diagnosis, the aetiology and clinical behaviour of abdominal wall neoplasms, and the surgical and non-surgical treatments for these tumours.
HIV disease and the abdominal surgeon
Authors: Muller Elmi , Boutall Adam
Published: October 2022

This chapter evaluates important considerations for HIV positive patients undergoing surgery and highlight some of the important issues reported in the literature. Clinical data have been pooled from different cohorts in order to show some of the common issues encountered in HIV positive transplantation. Searches were performed on MEDLINE via PubMed, EMBASE, Cochrane CENTRAL to create a comprehensive table for current evidence for different issues currently encountered when transplanting HIV positive patients.
Anatomy and development of the duodenum and small intestine
Authors: Stringer Mark D.
Published: October 2022

The small intestine consists of the duodenum, jejunum, and ileum. The combined length of the jejunum and ileum measured from the duodenojejunal flexure to the ileocaecal junction in vivo varies considerably but is approximately 5 m in adults. The duodenum extends from the stomach to the duodenojejunal flexure; the proximal two-fifths of the remaining small intestine is the jejunum and the distal three-fifths is the ileum. The duodenum is mostly retroperitoneal while the jejunum and ileum are intraperitoneal and suspended by a fat-laden mesentery containing blood vessels, lymphatics, and nerves. There is no clear anatomical transition between the jejunum and the ileum but the morphology and histology of the proximal and distal regions of the small bowel differ significantly. The wall of the small intestine consists of a mucosa, submucosa, muscularis externa, and serosa. The mucosal surface is characterized by numerous intestinal villi, which are covered on their luminal surface by enterocytes bearing luminal microvilli. The small intestine is adapted for fluid, electrolyte, and nutrient absorption. Intestinal stem cells located in the intestinal crypts are the source of most cell types of the intestinal epithelium. The functions of the small intestine are regulated by the enteric nervous system, which is modulated by extrinsic autonomic nerves. The development of the human small intestine is largely complete by the end of the 12th week after fertilization.
Intestinal fistulae
Authors: Allan Philip J. , Epstein Jonathan , Lal Simon
Published: October 2022

Intestinal fistulae typically follow surgical procedures, often when the operation has been performed in the emergency setting, or in individuals with specific underlying conditions, such as inflammatory bowel disease or cancer. The key management of these patients should follow an algorithm, an acronym of SNAP—sepsis, nutrition, anatomy, and plan. This allows an experienced multidisciplinary team to work through and treat the patient effectively as problems are encountered to bring the patient to the optimal physical and psychological readiness for reconstructive surgery with the aim of restoring intestinal continuity. This chapter looks at the different types of intestinal fistulae that occur, the impact on patients, and their management.
Techniques of small bowel surgery
Authors: Kim David H. , Kao Lillian S.
Published: October 2022

Surgery of the small bowel comprises a significant portion of the repertoire required of the general surgeon. Understanding small bowel anatomy and core technical principles will allow him or her to navigate almost any clinical scenario. Multiple options exist for reconstruction, and familiarity with these gives the surgeon flexibility to confront unexpected situations. Sound decision-making and meticulous technique at the index operation help prevent complications such as anastomotic leaks. Furthermore, knowledge of potential complications allows for a high index of suspicion and early intervention. Treatment and outcomes of complications depend on the actual type and timing of detection.
Tourette Syndrome
Authors: Martino Davide , Leckman James
Published: October 2022

Tourette syndrome (TS) is now recognized as a common neurodevelopmental disorder affecting children and adults. It has gained increasingly public awareness and scientific interest worldwide. Knowledge of its clinical presentation and available treatment approaches has increased dramatically over the last two decades. Tourette Syndrome offers a unique, comprehensive, and up-to-date overview of TS. The volume highlights the latest findings regarding clinical presentation, underlying genetic, epigenetic, immunological, and neurobiological causal mechanisms, and state-of-the-art therapies. Importantly, in this digital world of ours and given the ongoing pandemic, this volume also provides a detailed review of the latest available multifaceted and multidisciplinary treatment options including psychoeducational and cognitive-behavioral interventions, many of which can now be accessed online. More than 50 leading scientists and expert clinicians from across the globe authored the chapters. Readers can also access videotaped presentations recorded by several of these scholars. Fortunately, several of these presentations include individuals with TS and related conditions who have graciously volunteered to discuss their life’s journey. This volume is a useful source for a wide audience of scholars and clinicians, all of whom will have access to what is known so far on TS and related conditions within their area of expertise. It provides readers an opportunity to expand and update their knowledge base in other areas of science and advocacy. Families and health professionals will also have access to updates from a broad range of advocacy associations and organizations all around the world that are dedicated to improving lives of individuals with TS.
Tourette Syndrome: Circuits and Neurotransmitters
Authors: Singer Harvey S. , Augustine Farhan
Published: October 2022

Tourette syndrome (TS) is a complex disorder characterized by the presence of persistent, fluctuating motor and vocal tics and the coexistence of neuropsychological difficulties. The pathobiology of TS involves the complex and integrated cortico-striatal-thalamo-cortical (CSTC) circuits. This chapter systematically analyzes the involvement in TS of all the neurotransmitter systems relevant to CSTC circuits. A major role for dopamine continues to be the most consistently observed neurotransmitter change in this condition. Of the various dopaminergic hypotheses proposed, an alteration of the tonic-phasic neurotransmitter release system appears most viable. However, it remains highly likely that TS patients exhibit dysfunction in several neurotransmitter systems, although new evidence is warranted to better understand the dysfunction of non-dopaminergic systems, particularly serotonergic, glutamatergic, and GABAergic ones.
General Introduction
Authors: Barnard David
Published: October 2022

This chapter surveys changes in the landscape of palliative care since the first edition and presents an overview of the book’s overarching themes: (1) there are frequent discrepancies between professionals’ and patients’ or families’ assessments of the effectiveness of care; (2) the transition from active treatment (primarily curative or life-prolonging in intent) to palliative treatment (primarily aimed at comfort and support) is often a gradual, confusing, ambivalent process; (3) differences in socioeconomic status, race, and ethnicity between patients, families, and their professional caregivers can complicate and even undermine effective palliative care; (4) relationships between patients, families, and caregivers pass through many stages over time; (5) professional caregivers, as well as patients and families, bring their histories of death and loss into the caring relationship; (6) patients who display a religiously or spiritually grounded serenity as death approaches sometimes provoke suspicion or skepticism in their professional caregivers, who worry about unexpressed anxieties and fears; (7) growth and change are possible throughout the time of a person’s dying, for individuals and for their relationships; (8) people have varying success in trying to maintain a sense of normalcy and continuity in their sense of personal identity in advanced illness.
Shamira Cook
Authors: Lambrinidou Yanna
Published: October 2022

Shamira Cook, a poor, Black, single mother with a history of heroin addiction, was 34 years old when diagnosed with cancer. She saw her illness as an urgent call to share her story with the world and set the record straight on who she really was. She was also determined to do everything possible to extend her life. For some members of her hospice team, her unwillingness to surrender to the institutionally preferred plan of care was a challenge. It raised questions about whether she understood the gravity of her condition, and it created disagreements about whether she was “hospice-appropriate” or a “drain” on the system. Underneath the tensions that arose lay conflicting ideologies about hospice’s obligation to patients who do not fit the dominant patient profile. Is it to “nudge” them into an end-of-life path that complies with institutional ideals or to accompany them on a journey that might be less familiar to hospice staff but that grants them more control? This case offers a glimpse of end-of-life care when institutions take positions that contradict the patient’s wishes. It also raises questions about institutional racism and classism as well as discrimination against people with substance abuse pasts.
Sadie Fineman
Authors: Boston Patricia
Published: October 2022

Sadie Fineman was 80 years old when her doctors discovered that she had a large cancerous mass in her pancreas. Despite a course of experimental therapy, the tumor continued to grow, and the best option that Mrs. Fineman’s doctors could offer was palliative care. Mrs. Fineman and her family made it clear to the palliative care team that she wanted to be cared for at home, even though there were many times when the nursing care she required exceeded the knowledge and skills of her family. This was not her caregivers’ only challenge; the Fineman family insisted that the word “cancer” be avoided in all dealings with the patient, to keep the truth from her at all costs.
Trauma
Authors: Thurairatnam Rebecca , Mir Fauzia
Published: October 2022

Maxillofacial trauma forms a significant percentage of major trauma and anaesthetists are routinely involved in initial assessment, stabilization, and perioperative care of these patients. Anaesthetic considerations for maxillofacial trauma are discussed in this chapter, including a brief overview of the epidemiology, aetiology, and classification of maxillofacial trauma. Commonly associated injuries of relevance to the anaesthetist are also discussed. These include traumatic brain injuries and dural tears, cervical spine, pharyngeal, oesophageal, and ocular injuries, as well as iatrogenic maxillofacial trauma. Emergency airway management, the recognition of acute airway compromise, and specific airway management techniques are explored, including the applicability of failed tracheal intubation guidelines and the use of videolaryngoscopy in complex maxillofacial trauma. Preoperative assessment and preparation, intraoperative tracheal tube changes, and postoperative anaesthetic considerations in maxillofacial trauma patients are also discussed.
Malignancy
Authors: Gerstman Michelle , Lacey Orla J. , Kerawala Cyrus
Published: October 2022

Anaesthesia for oromaxillofacial malignancy surgery can range from minor diagnostic tissue biopsies to major cancer resection, neck dissection, and flap reconstructive procedures. However, the principles and approach remain the same—thorough airway evaluation (including radiological assessment and nasendoscopy), a planned and agreed airway management strategy, preparation for failure, and prioritization of patient oxygenation at all times. This chapter describes oromaxillofacial cancer epidemiology, the range of indications for cancer surgery, the essentials of airway assessment, the range of advanced airway management and oxygenation techniques, the fundamentals of intraoperative care, advanced tracheal extubation strategies, and procedure-specific guidance, including the principles of free flap reconstruction.
Other antihypertensive agents
Authors: Patil Shankar , Tayebjee Muzahir , Nadar Sunil K.
Published: October 2022

First-line agents for management of hypertension include beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, and diuretics. However, a sizeable proportion of patients have hard-to-treat hypertension or resistant hypertension, and require the addition of other agents such as alpha adrenergic blockers or centrally acting drugs. These drugs are not recommended for initiation of therapy in newly diagnosed hypertension. However, they are recommended as add-on therapy in difficult-to-treat hypertension. This chapter will review these so-called third- or fourth-line agents. It will also review agents that are currently being investigated which show huge potential in management of hypertension.
Expansion of the genetic code through reassignment of redundant sense codons using fully modified tRNA
Authors: McFeely Clinton A L , Dods Kara K , Patel Shivam S , Hartman Matthew C T
Published: October 2022

Breaking codon degeneracy for the introduction of non-canonical amino acids offers many opportunities in synthetic biology. Yet, despite the existence of 64 codons, the code has only been expanded to 25 amino acids in vitro. A limiting factor could be the over-reliance on synthetic tRNAs which lack the post-transcriptional modifications that improve translational fidelity. To determine whether modified, wild-type tRNA could improve sense codon reassignment, we developed a new fluorous method for tRNA capture and applied it to the isolation of roughly half of the Escherichia coli tRNA isoacceptors. We then performed codon competition experiments between the five captured wild-type leucyl-tRNAs and their synthetic counterparts, revealing a strong preference for wild-type tRNA in an in vitro translation system. Finally, we compared the ability of wild-type and synthetic leucyl-tRNA to break the degeneracy of the leucine codon box, showing that only captured wild-type tRNAs are discriminated with enough fidelity to accurately split the leucine codon box for the encoding of three separate amino acids. Wild-type tRNAs are therefore enabling reagents for maximizing the reassignment potential of the genetic code.
A cryptic transactivation domain of EZH2 binds AR and AR’s splice variant, promoting oncogene activation and tumorous transformation
Authors: Wang Jun , Park Kwang-Su , Yu Xufen , Gong Weida , Earp H Shelton , Wang Gang Greg , Jin Jian , Cai Ling
Published: October 2022

Enhancer of Zeste Homolog 2 (EZH2) and androgen receptor (AR) are crucial chromatin/gene regulators involved in the development and/or progression of prostate cancer, including advanced castration-resistant prostate cancer (CRPC). To sustain prostate tumorigenicity, EZH2 establishes non-canonical biochemical interaction with AR for mediating oncogene activation, in addition to its canonical role as a transcriptional repressor and enzymatic subunit of Polycomb Repressive Complex 2 (PRC2). However, the molecular basis underlying non-canonical activities of EZH2 in prostate cancer remains elusive, and a therapeutic strategy for targeting EZH2:AR-mediated oncogene activation is also lacking. Here, we report that a cryptic transactivation domain of EZH2 (EZH2TAD) binds both AR and AR spliced variant 7 (AR-V7), a constitutively active AR variant enriched in CRPC, mediating assembly and/or recruitment of transactivation-related machineries at genomic sites that lack PRC2 binding. Such non-canonical targets of EZH2:AR/AR-V7:(co-)activators are enriched for the clinically relevant oncogenes. We also show that EZH2TAD is required for the chromatin recruitment of EZH2 to oncogenes, for EZH2-mediated oncogene activation and for CRPC growth in vitro and in vivo. To completely block EZH2’s multifaceted oncogenic activities in prostate cancer, we employed MS177, a recently developed proteolysis-targeting chimera (PROTAC) of EZH2. Strikingly, MS177 achieved on-target depletion of both EZH2’s canonical (EZH2:PRC2) and non-canonical (EZH2TAD:AR/AR-V7:co-activators) complexes in prostate cancer cells, eliciting far more potent antitumor effects than the catalytic inhibitors of EZH2. Overall, this study reports a previously unappreciated requirement for EZH2TAD for mediating EZH2’s non-canonical (co-)activator recruitment and gene activation functions in prostate cancer and suggests EZH2-targeting PROTACs as a potentially attractive therapeutic for the treatment of aggressive prostate cancer that rely on the circuits wired by EZH2 and AR.
Structural and functional determinants of the archaeal 8-oxoguanine-DNA glycosylase AGOG for DNA damage recognition and processing
Authors: Franck Coste , Stéphane Goffinont , Julien Cros , Virginie Gaudon , Martine Guérin , Norbert Garnier , Fabrice Confalonieri , Didier Flament , Josef Suskiewicz Marcin , Bertrand Castaing
Published: October 2022

8-Oxoguanine (GO) is a major purine oxidation product in DNA. Because of its highly mutagenic properties, GO absolutely must be eliminated from DNA. To do this, aerobic and anaerobic organisms from the three kingdoms of life have evolved repair mechanisms to prevent its deleterious effect on genetic integrity. The major way to remove GO is the base excision repair pathway, usually initiated by a GO-DNA glycosylase. First identified in bacteria (Fpg) and eukaryotes (OGG1), GO-DNA glycosylases were more recently identified in archaea (OGG2 and AGOG). AGOG is the less documented enzyme and its mode of damage recognition and removing remains to be clarified at the molecular and atomic levels. This study presents a complete structural characterisation of apo AGOGs from Pyrococcus abyssi (Pab) and Thermococcus gammatolerans (Tga) and the first structure of Pab-AGOG bound to lesion-containing single- or double-stranded DNA. By combining X-ray structure analysis, site directed mutagenesis and biochemistry experiments, we identified key amino acid residues of AGOGs responsible for the specific recognition of the lesion and the base opposite the lesion and for catalysis. Moreover, a unique binding mode of GO, involving double base flipping, never observed for any other DNA glycosylases, is revealed. In addition to unravelling the properties of AGOGs, our study, through comparative biochemical and structural analysis, offers new insights into the evolutionary plasticity of DNA glycosylases across all three kingdoms of life.
The protein common assembly database (ProtCAD)—a comprehensive structural resource of protein complexes
Authors: Xu Qifang , Dunbrack Roland L
Published: October 2022

Proteins often act through oligomeric interactions with other proteins. X-ray crystallography and cryo-electron microscopy provide detailed information on the structures of biological assemblies, defined as the most likely biologically relevant structures derived from experimental data. In crystal structures, the most relevant assembly may be ambiguously determined, since multiple assemblies observed in the crystal lattice may be plausible. It is estimated that 10–15% of PDB entries may have incorrect or ambiguous assembly annotations. Accurate assemblies are required for understanding functional data and training of deep learning methods for predicting assembly structures. As with any other kind of biological data, replication via multiple independent experiments provides important validation for the determination of biological assembly structures. Here we present the Protein Common Assembly Database (ProtCAD), which presents clusters of protein assembly structures observed in independent structure determinations of homologous proteins in the Protein Data Bank (PDB). ProtCAD is searchable by PDB entry, UniProt identifiers, or Pfam domain designations and provides downloads of coordinate files, PyMol scripts, and publicly available assembly annotations for each cluster of assemblies. About 60% of PDB entries contain assemblies in clusters of at least 2 independent experiments. All clusters and coordinates are available on ProtCAD web site (http://dunbrack2.fccc.edu/protcad).
PROTAC-DB 2.0: an updated database of PROTACs
Authors: Weng Gaoqi , Cai Xuanyan , Cao Dongsheng , Du Hongyan , Shen Chao , Deng Yafeng , He Qiaojun , Yang Bo , Li Dan , Hou Tingjun
Published: October 2022

Proteolysis targeting chimeras (PROTACs), which harness the ubiquitin-proteasome system to selectively induce targeted protein degradation, represent an emerging therapeutic technology with the potential to modulate traditional undruggable targets. Over the past few years, this technology has moved from academia to industry and more than 10 PROTACs have been advanced into clinical trials. However, designing potent PROTACs with desirable drug-like properties still remains a great challenge. Here, we report an updated online database, PROTAC-DB 2.0, which is a repository of structural and experimental data about PROTACs. In this 2nd release, we expanded the number of PROTACs to 3270, which corresponds to a 96% expansion over the first version. Meanwhile, the numbers of warheads (small molecules targeting the proteins of interest), linkers, and E3 ligands (small molecules recruiting E3 ligases) have increased to over 360, 1500 and 80, respectively. In addition, given the importance and the limited number of the crystal target-PROTAC-E3 ternary complex structures, we provide the predicted ternary complex structures for PROTACs with good degradation capability using our PROTAC-Model method. To further facilitate the analysis of PROTAC data, a new filtering strategy based on the E3 ligases is also added. PROTAC-DB 2.0 is available online at http://cadd.zju.edu.cn/protacdb/.
Sung Shu Chien: The founder of modern Chinese botany
Authors: Liu Huan , Huang Kaijing , Yuan Xuefan , Cheng Hao
Published: October 2022

Sung Shu Chien (钱崇澍, 1883–1965) (Fig. 1) was a famous botanist and educator in China, one of the founders of Chinese plant taxonomy, plant physiology, geobotany, and floristics. He devoted his whole life to scientific research and education, and was a founder of modern Chinese botany. Sung Shu Chien pioneered several research fields in modern Chinese botany. In 1916, he published the first literature in Latin on the naming and classification of plants. In the following year, he published the earliest thesis on the application of modern scientific methods of plant physiology in China. He wrote the first paper in the area of plant ecology and geobotany in China. He was a pioneer in the systematic study of the families Orchidaceae, Urticaceae, Fabaceae, and Ranunculaceae in China. From 1959 to 1965, he was the chief editor of “Flora of China” and was responsible for the section on Urticaceae (Yu, 1983). Sung Shu Chien initiated the research of plant taxonomy, plant physiology and plant ecology in China, and laid a solid foundation for the extensive research of vegetation, plant zoning and plant specialties in China (Chien et al., 1956). By skillfully combining research and education, he cultivated Chinese scientific and technological talents in botany.