A novel Monash Pouch diet in patients with an ileoanal pouch is tolerable and has favorable metabolic luminal effects.

Aims: To evaluate a whole-food diet strategy (the Monash Pouch diet [MPD]) designed based on the interacting roles dietary factors play with pouch health. Specifically, its tolerability and acceptability, whether it achieved its dietary and metabolic goals, and the effects on symptoms and inflammation were examined. Methods: In a 6-week open-label trial, patients with ileoanal pouches educated on the MPD were assessed regarding diet tolerability and acceptance, food intake (7-day food diaries), pouch-related symptoms (clinical pouchitis disease activity index), and, in 24-h fecal samples, calprotectin, fermentative biomarkers, and volatile organic compounds (VOC). Results: Of 12 patients, 6 male, mean (SD) age 55 (5) and pouch age 13 (2) years, one withdrew with partial small bowel obstruction. Tolerability was excellent in 9 (75%) and acceptance was high (81%). Targeted changes in dietary intake were achieved. Fecal branched- to short-chain fatty acid ratio increased by median 60 [IQR: 11-80]% (P = 0.02). Fecal VOCs for 3 compounds were also increased, 2-methyl-5-propan-2-ylcyclohexa-1,3-diene (Fold-change [FC] 2.08), 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane (FC 3.86), propan-2-ol (FC 2.10). All six symptomatic patients achieved symptomatic remission (P = 0.03). Fecal calprotectin at baseline was 292 [176-527] µg/g and at week 5 was 205 [148-310] µg/g (P = 0.72). Conclusion: Well tolerated and accepted, the MPD achieved targeted changes in intakes and fermentation of carbohydrates relative to that of protein. There were signals of improvement in symptoms. These results indicate the need for a randomized-controlled trial. (Trial registration: ACTRN12621000374864; https://www.anzctr.org.au/ACTRN12621000374864.aspx).

End-of-life care for people with severe mental illness: mixed methods systematic review and thematic synthesis of published case studies (the MENLOC study).

OBJECTIVES: People with severe mental illness (SMI) have significant comorbidities and reduced life expectancy. The objective of the review reported in this paper was to synthesise material from case studies relating to the organisation, provision and receipt of care for people with SMI who have an end-of-life (EoL) diagnosis. DESIGN: Systematic review and thematic synthesis. DATA SOURCES: MEDLINE, PsycINFO, EMBASE, HMIC, AMED, CINAHL, CENTRAL, ASSIA, DARE and Web of Science from inception to December 2019. Supplementary searching for additional material including grey literature along with 62 organisational websites. RESULTS: Of the 11 904 citations retrieved, 42 papers reporting 51 case studies were identified and are reported here. Twenty-five of the forty-two case study papers met seven, or more quality criteria, with eight meeting half or less. Attributes of case study subjects included that just over half were men, had a mean age of 55 years, psychotic illnesses dominated and the EoL condition was in most cases a cancer. Analysis generated themes as follows diagnostic delay and overshadowing, decision capacity and dilemmas, medical futility, individuals and their networks, care provision. CONCLUSIONS: In the absence of high-quality intervention studies, this evidence synthesis indicates that cross disciplinary care is supported within the context of established therapeutic relationships. Attention to potential delay and diagnostic overshadowing is required in care provision. The values and preferences of individuals with severe mental illness experiencing an end-of-life condition should be recognised. PROSPERO REGISTRATION NUMBER: CRD42018108988.

End of life care for people with severe mental illness: Mixed methods systematic review and thematic synthesis (the MENLOC study).

BACKGROUND: Parity of esteem means that end-of-life care for people with severe mental illness should be of equal quality to that experienced by all. AIM: To synthesise international, English language, research and UK policy and guidance relating to the organisation, provision, and receipt of end-of-life care for people with severe mental illness. DESIGN: A mixed methods systematic review was conducted following the Evidence for Policy and Practice Information and Co-ordinating Centre approach and informed by a stakeholder group. We employed thematic synthesis to bring together data from both qualitative and quantitative studies, and from non-research material. We assessed the strength of synthesised findings using the Confidence in the Evidence from Reviews of Qualitative Research (CERQual) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approaches. DATA SOURCES: Ten electronic databases were searched from inception to December 2019, along with 62 organisational websites. Quality appraisal was conducted using Critical Appraisal Skills Programme checklists or other study design-specific alternatives as necessary. RESULTS: Of the 11,904 citations retrieved, 34 research publications were included plus 28 non-research items. The majority of research was of high or acceptable quality. An overarching synthesis including 52 summary statements, with assessments of confidence in the underpinning evidence, was produced using four themes: Structure of the system; Professional issues; Contexts of care; and Living with severe mental illness. CONCLUSIONS: Implications for services and practice reflect evidence in which there is a high degree of confidence. Partnership should be developed across the mental health and end-of-life systems, and ways found to support people to die where they choose. Staff caring for people with severe mental illness at the end-of-life need education, support and supervision. End-of-life care for people with severe mental illness requires a team approach, including advocacy. Proactive physical health care for people with severe mental illness is needed to tackle problems of delayed diagnosis.

Propionic acid metabolism and poly-3-hydroxybutyrate-co-3-hydroxyvalerate production by a prpC mutant of Herbaspirillum seropedicae Z69.

Polyhydroxyalkanoates (PHAs) are thermoplastic polyesters produced by a wide range of bacteria as carbon and energy reserves. PHA accumulation is typically increased under unbalanced growth conditions and with carbon source in excess. Although polyhydroxybutyrate (PHB) could be used for specific applications, it is brittle and not a useful alternative for plastics like polypropylene. Far more useful polypropylene-like PHAs, are copolymers composed of 3-hydroxybutyrate and 3-hydroxyvalerate, P(3HB-co-3HV). Propionic acid is one of the carbon sources that can be used to generate 3HV. A mutant derived from Herbaspirillum seropedicae Z69, a strain previously described as capable of producing P(3HB-co-3HV) from propionic acid, was constructed to increase 3HV biosynthetic efficiency. The strategy involved elimination of a catabolic route for propionyl-CoA by deficiency marker exchange of a selected gene. The mutant (Z69Prp) was constructed by elimination of the 2-methylcitrate synthase (PrpC) gene of the 2-methylcitrate cycle for propionate catabolism. Strain Z69Prp was unable to grow on sodium propionate, but in cultures with glucose-propionate accumulated 50% of its dry weight as copolymer. Z69Prp had 14.1 mol% 3HV; greater than that of strain Z69 (2.89 mol%). The 3HV yield from propionic acid (Y3HV/prop) was 0.80 g g-1, and below the maximum theoretical value (1.35 g g-1).

Patient-Reported Outcomes following Single- and Multiple-Radius Total Knee Replacement: A Randomized, Controlled Trial.

Although single-radius (SR) designs of total knee replacement (TKR) have theoretical benefits, the clinical advantage conferred by such designs is unknown. The aim of this randomized, controlled study was to compare the short-term clinical outcomes of the two design rationales. A total of 105 knees were randomized to receive either a single radius (Scorpio, Stryker; SR Group) or multiple radius (AGC, Zimmer Biomet; MR group) TKR. Patient-reported outcomes (Oxford Knee Score [OKS] and Knee Society Score [KSS]) were collected at 6 weeks, 6 months, and 1 year following surgery. No knees were revised. There was no difference in primary outcomes: OKS was 39.5 (95% confidence interval [CI]: 36.9-42.1) in the SR group and 38.1 (95% CI: 36.0-40.3) in the MR group (p = 0.40). KSS was 168.4 (95% CI: 159.8-177.0) in the SR group; 159.5 (95% CI 150.5-168.5) in the MR group (p = 0.16). There was a small but statistically significant difference in the degree of change of the objective subscale of the KSS, favoring the SR design (p = 0.04), but this is of uncertain clinical relevance. The reported benefits of SR designs do not provide demonstrable functional advantages in the short term.

Pseudomembranous tracheitis caused by Aspergillus fumigatus in the setting of high grade T-cell lymphoma.

Pseudomembranous tracheitis (PMT) is a rare condition most commonly caused by fungal or bacterial infection that is characterized by a pseudomembrane that partially or completely covers the tracheobronchial tree. PMT is most commonly found in immunocompromised patient populations, such as post-chemotherapy, AIDS, post-transplant and hematological malignancies. Due to its rarity, PMT is often not included in the differential diagnosis. This case describes a 65 year old male with persistent fever and refractory cough despite high dose empiric antibiotics. Subsequent bronchoscopy with biopsy revealed pseudomembranous tracheitis due to Aspergillus fumigatus in the setting of T-cell lymphoma. PMT should be considered in the differential diagnosis of refractory cough in the immunocompromised population. However, it has been described in patients with nonspecific respiratory symptoms such as dyspnea, cough, and other airway issues.

Parasexuality in genitourinary investigations: a qualitative study.

BACKGROUND: Genitourinary investigations are performed on a large proportion of middle-aged and older men and the majority undergo investigations for prostate issues. The effects that genitourinary disease can have on men depend on the type of problem, investigations required and treatment including impotence, gynaecomastia and urinary incontinence that have lasting devastating physical, social and psychological effects. The aim was to explore older men's experience and views of intimate and intrusive genitourinary investigations and specifically to develop hypotheses and theories concerning gender and sexuality issues in intimate genitourinary investigations. METHODS: Written informed consent was obtained for this qualitative study. Data were collected through one-off, semi-structured interviews involving 15 men in the first year following patient's last urological procedure. Initially, multiple themes were identified and when analysed further concepts were repeatedly present. As the urological investigations were limited to men, gender and sexuality became prominent issues in the data. RESULTS: On analysis, the term parasexuality appeared to explain the dynamic of the situation. Parasexuality is a modified form of sexuality which is channelled and limited to maintain propriety. This was not expressed as sexuality in its overt, explicit sense, but instead a type of covert sexuality where professional boundaries are maintained but nonetheless undercurrents remain. This managed version of sexuality created a common currency by which interactions between staff and patients could take place safely. Feeding into parasexuality were gender role stereotypes and for some of the participants this reflected their own experience, context, historical and cultural norms. Intimate contact in the form of exposure and handling of the participants' genitalia during the investigations particularly challenged the boundaries of parasexuality. In order to remain parasexual, many of the participants suppressed their sexuality. Viewing staff as professional was an additional strategy used by participants to limit any sexuality as parasexuality. CONCLUSION: This study has contributed towards the appeal for more studies to examine privacy perceptions of patients in genitalia-related care, however, it is by no means definitive. Parasexuality goes some way to explain the dynamics of communication between older men and health care professionals during genitourinary investigations.

Stressors and coping mechanisms in live-related renal transplantation.

AIM: To explore donor and recipient experiences of stressors and coping mechanisms associated with live-related renal transplantation. BACKGROUND: Live-related renal transplantation is an effective and efficient treatment for end-stage kidney disease, but is also associated with a variety of stressors. DESIGN: Longitudinal, phenomenological study. METHODS: Eleven live kidney donors and their recipients (n = 22) were recruited from a regional renal transplant centre in South-West England. Data were collected through three recorded, semi-structured interviews, conducted pretransplant and at three and 10 months post-transplant. Interviews were transcribed verbatim, analysed using a process of thematic analysis and validated through a constructive process of inter-rater reliability. RESULTS: End-stage kidney disease, dialysis and live transplantation produced a variety of stressors for donors and recipients. Common stressors included the live transplantation decision-making process, the prospect of surgery and postoperative recovery, follow-up care for donors and, in particular, concern for each other, especially amongst recipients. The main stressor, however, was fear of transplant failure. Participants used a variety of problem- and emotion-focused coping mechanisms to deal with these stressors and donors and recipients actively supported each other through the transplantation process. CONCLUSION: Renal transplantation remains the treatment of choice for most patients with end-stage kidney disease but is a source of considerable stress for donors and especially recipients and subsequently requires a range of coping mechanisms, including social support. RELEVANCE TO CLINICAL PRACTICE: Patients need to be adequately informed of the risks associated with transplantation and provided with appropriate emotional care and support throughout the transplantation process. Health professionals also need to be mindful of assessing the needs and managing realistic expectations of patients and their families.

Suppressor of fused controls mid-hindbrain patterning and cerebellar morphogenesis via GLI3 repressor.

Sonic Hedgehog and its GLI transcriptional effectors control foliation complexity during cerebellar morphogenesis by promoting granule cell precursor proliferation. Here, we reveal a novel contribution of Sonic Hedgehog-GLI signaling to cerebellar patterning and cell differentiation by generating mice with targeted deletion of Suppressor of Fused (SuFu), a regulator of Sonic Hedgehog signaling, in the mid-hindbrain. Postnatal SuFu-deficient mice exhibit impaired motor coordination and severe cerebellar mispatterning. SuFu conditional knock-out embryos display abnormal mid-hindbrain morphology associated with misexpression of Fgf8, and delayed differentiation and abnormal migration of major cerebellar cell types. Sonic Hedgehog is ectopically expressed in the external granule layer and Hedgehog signaling is upregulated. While expression of full-length GLI transcriptional activators downstream of Hedgehogs is markedly reduced, a processed form of GLI3, a transcriptional repressor, is essentially lost. Genetic expression of a Gli3 allele encoding GLI3 repressor in SuFu-deficient mice largely rescues abnormal cerebellar patterning and cell differentiation observed in mice with SuFu deficiency alone. Together, our data demonstrate that SuFu controls cerebellar patterning and cell differentiation in a GLI3 repressor-dependent manner.

Canonical WNT/beta-catenin signaling is required for ureteric branching.

WNT/beta-catenin signaling has an established role in nephron formation during kidney development. Yet, the role of beta-catenin during ureteric morphogenesis in vivo is undefined. We generated a murine genetic model of beta-catenin deficiency targeted to the ureteric bud cell lineage. Newborn mutant mice demonstrated bilateral renal aplasia or renal dysplasia. Analysis of the embryologic events leading to this phenotype revealed that abnormal ureteric branching at E12.5 precedes histologic abnormalities at E13.5. Microarray analysis of E12.5 kidney tissue identified decreased Emx2 and Lim1 expression among a small subset of renal patterning genes disrupted at the stage of abnormal branching. These alterations are followed by decreased expression of genes downstream of Emx2, including Lim1, Pax2, and the ureteric tip markers, c-ret and Wnt 11. Together, these data demonstrate that beta-catenin performs essential functions during renal branching morphogenesis via control of a hierarchy of genes that control ureteric branching.

At the crossroads between tension-type headache and fibromyalgia.

Fibromyalgia syndrome and tension-type headache have multiple clinical features in common, and pathogenic mechanisms partly overlap. Significant differences need to be recognized as well. Studying the correlations of these often comorbid conditions represents a unique opportunity to gain insight into their pathophysiology and that of other chronic pain syndromes, to increase the accuracy of their diagnosis, and to improve the therapeutic armamentarium.

Control of murine kidney development by sonic hedgehog and its GLI effectors.

Sonic hedgehog (SHH) controls cell differentiation and morphogenesis in many tissues and species. The mammalian kidney is a paradigm for studying epithelial-mesenchymal interactions and growth factor signaling during embryogenesis. Here, we review our recent findings demonstrating that SHH is required for normal murine kidney development. During renal morphogenesis, SHH controls a hierarchy of genes including renal patterning genes, cell cycle modulators, and GLI family members. Our investigation of GLI protein processing and binding of GLI activators and repressor to SHH target genes provide insight into the molecular mechanisms by which SHH and its GLI family of effectors control renal embryogenesis. Further, we highlight the roles of BMP, WNT and FGF signaling during renal development and discuss possible interactions of these pathways with SHH signaling.

Iron depletion affects nitrogenase activity and expression of nifH and nifA genes in Herbaspirillum seropedicae.

Herbaspirillum seropedicae Z67 is a nitrogen-fixing bacterium able to colonize the rhizosphere and the interior of several plants. As iron is a key element for nitrogen fixation, we examined the response of this microorganism to iron deficiency under nitrogen fixing conditions. We identified a H. seropedicae exbD gene that was induced in response to iron limitation and is involved in iron homeostasis. We found that an exbD mutant grown in iron-chelated medium is unable to fix nitrogen. Moreover, we provide evidence that expression of the nifH and nifA genes is iron dependent in a H. seropedicae genetic background.

Accelerated rehabilitation after total knee replacement.

This study records the length of hospital stay of 50 total knee arthroplasty patients involved in an accelerated postoperative rehabilitation protocol, and a control group of patients undergoing routine rehabilitation. This protocol involved modifications to normal knee replacement procedure, including infiltration of bupivacaine and adrenaline to the divided tissue layers at the time of surgery, spinal anaesthesia, and mobilisation on the day of surgery. These modifications were combined with an organised multidisciplinary approach anticipating issues that may delay discharge. In addition, patients and hospital staff were encouraged to expect an earlier discharge from the hospital. The mean length of hospital stay after surgery was reduced to 3.6 (S.D. 1.0) days, from a previous departmental average of 10.5 days. The control group inpatient stay was 6.6 (S.D. 2.6) days. Plasma bupivacaine levels were found to be well within safe levels, and pain records indicated that the protocol did not cause increased levels of discomfort. American Knee Society and Oxford knee scores demonstrated good levels of knee function at 6 weeks post surgery. In addition, it was noted that no postoperative blood transfusions were required. This is regarded as a significant further benefit.

Comparison of bacterial inoculation and transcutaneous oxygen tension in the rabbit S1 perforator and latissimus dorsi musculocutaneous flaps.

Muscle and musculocutaneous flaps have been used reliably in reconstruction of soft-tissue defects for many years. Previous experimental studies have shown musculocutaneous flaps to be superior to the random pattern and fasciocutaneous flaps in the management of infected wounds. Over the past decade, perforator flaps have gained acceptance as alternative methods of reconstruction in the clinical setting that can decrease donor-site morbidity and hospital stay, and increase patient satisfaction. The authors theorized that perforator flaps may be able to handle infected wounds better than random pattern and fasciocutaneous flaps because their blood supply is essentially the same as many of their musculocutaneous counterparts. The goal of this study was to compare the S1 perforator-based skin flap and latissimus dorsi musculocutaneous flap in the dorsal flank of the rabbit with the introduction of bacteria to simulate both superficial and deep wound infection. Measurements of oxygen tension and regional perfusion index were performed on both types of flaps to ascertain their viability and capacity to heal. The authors found no statistical significance between latissimus dorsi musculocutaneous and S1 perforator flaps in the rabbit with respect to superficial and deep wound infections. The regional perfusion index was calculated for postoperative days 1, 2, and 4. No statistically significant difference between the two flaps using the regional perfusion index could be identified. Additionally, regional perfusion for both types of flaps was greater than 0.6, indicating that their capacity to heal wounds is similar.

Unicompartmental knee arthroplasty: an intermediate report of survivorship after the introduction of a new system with analysis of failures.

We describe the outcome of a series of 66 consecutive porous coated low contact stress (LCS) unicompartmental knee arthroplasty (UKA) cases performed in 52 patients for osteoarthritis (OA) by a single surgeon. Both survival, using the endpoint of revision for any cause, and knee function, using the Oxford knee score (OKS) as a validated outcome measure, were established in a retrospective review. At an average postoperative follow-up period of 5.9 years (range 5.1-6.6), there were 8 knees in patients who had died and 58 knees in those who were still living. We established the status of all knees, and prosthesis survival at 5 years was 89.7% (95% confidence interval, 81.6% to 97.7%). Technical errors were responsible for four of six failures and included progression of lateral compartment OA due to overcorrection, a medial tibial stress fracture due to poor pin placement, and a case where cement was required and poor cementing technique lead to early tibial component loosening. In the remaining 52 knees, the average preoperative OKS had improved significantly (p<0.0001) from 37.0 (range, 17-49) to a postoperative score of 20.5 (range, 13-32). We conclude that the functional results following UKA compare favourably to total knee arthropasty (TKA); however, the survivorship of this series does not match that of published reports of TKA. The introduction of a new system of UKA includes the risk of early failures due to surgeon error, even when a surgeon is competent in UKA, warranting careful surveillance during this period.

Bilateral breast reconstruction with the deep inferior epigastric perforator (DIEP) flap: an experience with 280 flaps.

Bilateral prophylactic mastectomy can reduce the incidence of breast cancer by 87 to 93% in high-risk individuals and is an appealing option for many patients if reconstruction can be provided with acceptable morbidity and outstanding esthetic results. Autogenous breast reconstruction techniques have evolved over the last 20 years to meet this goal. Familiarity with the deep inferior epigastric perforator (DIEP) flap led us to carry out simultaneous bilateral breast reconstruction with acceptable morbidity and superior esthetic outcome in 3 patient groups: (1) after bilateral prophylactic mastectomy, (2) after therapeutic and contralateral prophylactic mastectomy, and (3) after explantation of bilateral implant failures. A retrospective review of our experience with 280 flaps in 140 patients was performed. Average operating times, including time for implant removal or mastectomy and reconstruction, was 7.3 hours. Average hospitalization was 3.9 days. Significant perioperative complications occurred in 9 patients (6.4%); all returned to the operating room. This included 7 microvascular complications, 1 hematoma, 1 seroma, and 1 DVT. Less significant complications were divided into early and late. The early complications included 1.8% partial flap necrosis, 4.2% abdominal apron necrosis greater than 5 cm2, 2.9% seromas that required intervention, and 5.7% partial breast flap dehiscence. Late complications included 12.5% fat necrosis of any size and 2.1% hernia formation. Smoking, obesity, age, history of chest wall radiation, and flap size were evaluated as risk factors for increased morbidity.

A 10-year retrospective review of 758 DIEP flaps for breast reconstruction.

This study examined 758 deep inferior epigastric perforator flaps for breast reconstruction, with respect to risk factors and associated complications. Risk factors that demonstrated significant association with any breast or abdominal complication included smoking (p = 0.0000), postreconstruction radiotherapy (p = 0.0000), and hypertension (p = 0.0370). Ninety-eight flaps (12.9 percent) developed fat necrosis. Associated risk factors were smoking (p = 0.0226) and postreconstruction radiotherapy (p = 0.0000). Interestingly, as the number of perforators increased, so did the incidence of fat necrosis. There were only 19 cases (2.5 percent) of partial flap loss and four cases (0.5 percent) of total flap loss. Patients with 45 flaps (5.9 percent) were returned to the operating room before the second-stage procedure. Patients with 29 flaps (3.8 percent) were returned to the operating room because of venous congestion. Venous congestion and any complication were observed to be statistically unrelated to the number of venous anastomoses. Overall, postoperative abdominal hernia or bulge occurred after only five reconstructions (0.7 percent). Complication rates in this large series were comparable to those in retrospective reviews of pedicle and free transverse rectus abdominis musculocutaneous flaps. Previous studies of the free transverse rectus abdominis musculocutaneous flap described breast complication rates ranging from 8 to 13 percent and abdominal complication rates ranging from 0 to 82 percent. It was noted that, with experience in microsurgical techniques and perforator selection, the deep inferior epigastric perforator flap offers distinct advantages to patients, in terms of decreased donor-site morbidity and shorter recovery periods. Mastery of this flap provides reconstructive surgeons with more extensive options for the treatment of postmastectomy patients.

Breast reconstruction with gluteal artery perforator (GAP) flaps: a critical analysis of 142 cases.

Fujino was the first to introduce gluteal tissue as a free flap for breast reconstruction. The use of the musculocutaneous flap from the buttock in breast reconstruction has been championed by Shaw. Despite the initial enthusiasm for this area as a donor site, few other large series exist on the subject. Two decades of experience with this region as a donor site led to recognition of advantages and drawbacks. Furthermore, use of both the superior and inferior gluteal musculocutaneous flap was associated with certain important donor site complications and the use of vein grafts to allow for microvascular anastomosis. The evolution of free tissue transfer has progressed to the level of the perforator flap. This reconstructive technique allows elevation of tissue from any region consisting only of fat and skin. This minimizes donor site morbidity by allowing preservation of the underlying muscle and coverage of important structures in the region such as nerves. The superior and inferior gluteal perforator flaps have been used at our institution for breast reconstruction since 1993. The superior gluteal artery perforator (S-GAP) flap is our preferred method of breast reconstruction when the abdomen is not available or preferable. We report the result of this flap over the past 9 years and point out important surgical refinements, advantages, disadvantages, and lessons learned during this time.