Animation deformity is an undesirable outcome of subpectoral breast reconstruction that results in abnormal breast contraction with activity, breast pain, and increased implant visibility. Surgical ...correction requires implant removal and conversion of the reconstruction to a prepectoral plane. The authors present their institutional experience with their preferred surgical technique to treat this challenging problem and outline solutions for increased success in these patients.
A retrospective review was performed of all patients undergoing conversion of their subpectoral breast reconstruction to a prepectoral plane at the authors' institution. Patient demographics and surgical details were analyzed, and postoperative outcomes and morbidity were assessed. The effects of changing operative strategies on enhanced success are also reported.
A total of 80 breast conversions were performed over a 2.5-year period. All patients demonstrated resolution of animation deformity at a mean follow-up of 15.2 months. Two reconstructions (2.5 percent) required an unplanned return to the operating room, and 11 reconstructions (13.8 percent) were treated for infection. Preconversion fat grafting and the use of acellular dermal matrix were both associated with a reduced incidence of postoperative asymmetry and capsular contracture (p < 0.05). There were no reconstructive failures associated with conversion to a prepectoral pocket.
Treatment of animation deformity in the reconstructed patient can be safely performed by surgical conversion to a prepectoral plane. The use of acellular dermal matrix, and preconversion fat grafting, in appropriate patients can improve results. The authors promote this operative algorithm for all reconstructive patients experiencing symptomatic animation deformity with subpectoral breast reconstruction.
Therapeutic, IV.
Escherichia coli-based cell extract is a vital component of inexpensive and high-yielding cell-free protein synthesis reactions. However, effective preparation of E. coli cell extract is limited to ...high-pressure (French press-style or impinge-style) or bead mill homogenizers, which all require a significant capital investment. Here we report the viability of E. coli cell extract prepared using equipment that is both common to biotechnology laboratories and able to process small volume samples. Specifically, we assessed the low-capital-cost lysis techniques of: (i) sonication, (ii) bead vortex mixing, (iii) freeze-thaw cycling, and (iv) lysozyme incubation to prepare E. coli cell extract for cell-free protein synthesis (CFPS). We also used simple shake flask fermentations with a commercially available E. coli strain. In addition, RNA polymerase was overexpressed in the E. coli cells prior to lysis, thus eliminating the need to add independently purified RNA polymerase to the CFPS reaction. As a result, high-yielding E. coli-based extract was prepared using equipment requiring a reduced capital investment and common to biotechnology laboratories. To our knowledge, this is the first successful prokaryote-based CFPS reaction to be carried out with extract prepared by sonication or bead vortex mixing.
Gene therapy has the potential to offer people with haemophilia (PwH) a life free from bleeding and the burden posed by current treatment regimens. To date, gene therapy has only been available in ...clinical trial settings, to PwH without pre-existing or historical factor inhibitors, significant concomitant liver damage or pre-existing neutralising antibodies to the adeno-associated viruses used to deliver the therapy. Thus, most PwH treated at centres not currently involved in gene therapy trials, either as a referral/follow-up centre or as a dosing centre, have been unable to access the therapy. This Exigency sub-study aims to gain a greater understanding of the opinions of PwH in the United Kingdom who have not had access to gene therapy: asking what they understand, what concerns they have, and whether they perceive any barriers preventing their access to gene therapy.
Twenty-three PwH were approached; 14 consented, and one withdrew prior to interview. The mean age of the participants was 35.7 years (range 25-74 years). Eleven had haemophilia A and two haemophilia B. Two were treated with standard half-life factor products, five with extended half-life products, five with a FVIII mimetic and one with a clinical trial product. One family member (a participant's partner) was also interviewed. The participants identified four barriers to gene therapy: concerns about the process of gene therapy (Expectations), uncertainty about the results (outcomes), (Access) to treatment, and a lack of understanding about gene therapy (education).
This Exigency study subgroup sees gene therapy as a positive treatment development that promises an improved quality of life. For this participant group, four issues impact their decision to undergo gene therapy. If the promise of gene therapy is to be realised, these barriers need to be acknowledged and addressed by healthcare professionals, patient organisations, and gene therapy providers.
Gene therapy has the potential to change the life experience of people with haemophilia and family members. Few studies have sought to explore the impact of gene therapy on both individuals and ...families. The aim of this study was to capture real-life experiences of gene therapy in People with haemophilia and their families.
Sixteen participants with severe haemophilia (11 haemophilia A, five haemophilia B), mean age 41.4 years (range 23-75 years), took part in a single qualitative interview; ten were accompanied by a family member. Mean time since transfection was 3.56 years (range 1-10 years). Participants saw their involvement in gene therapy as a positive experience, freeing them from the personal burden of haemophilia and furthering treatment options for the wider haemophilia community. However, participants reported being unprepared for the side effects of immunosuppression. Some also reported feeling unsupported and having little control over what was happening as their factor levels became the focus of the process.
The results suggest that strategies need to be put into place to enable PwH fully to understand the process of gene therapy, and thereby make an informed choice as to whether it is a treatment they might wish for themselves. These include early and ongoing education, increased provision of psychosocial support and ongoing qualitative research.
Objective: To review the evidence for "the Mellanby effect", that is, whether the response to a given blood alcohol concentration (BAC) is more marked when BAC is rising than at the same ...concentration when BAC is falling.
Methods: We systematically searched the databases EMBASE, Medline, and Scopus up to and including December 2016 using text words "tolerance", "ascending", "descending" or "Mellanby" with Medline term "exp *alcohol/" or "exp *drinking behavior/" or equivalent. Articles were identified for further examination by title or abstract; full text articles were retained for analysis if they dealt with acute (within dose) alcohol tolerance in human subjects and provided quantitative data on both the ascending and descending parts of the BAC-time curve. Reference lists of identified works were scanned for other potentially relevant material. We extracted and analyzed data on the subjective and objective assessment of alcohol effects.
Results: We identified and screened 386 unique articles, of which 127 full-text articles were assessed; one provided no qualitative results, 62 involved no human study, 25 did not consider acute tolerance within dose, and 13 failed to provide data on both ascending and descending BAC. We extracted data from the 26 remaining articles. The studies were highly heterogeneous. Most were small, examining a total of 770 subjects, of whom 564 received alcohol and were analyzed in groups of median size 10 (range 5-38), sometimes subdivided on the basis of drinking or family history. Subjects were often young white men. Doses of alcohol and rates of administration differed. Performance was assessed by at least 26 different methods, some of which measured many variables. We examined only results of studies which compared results for a given alcohol concentration (C) measured on the ascending limb (C
up
) and the descending limb (C
down
) of the BAC-time curve, whether in paired or parallel-group studies. When subjects were given alcohol in more than one session, we considered results from the first session only. Rating at C
down
was better than at C
up
for some measures, as expected if the Mellanby effect were operating. For example, subjects rated themselves less intoxicated on the descending limb than at the same concentration on the ascending limb in 12/13 trials including 229 subjects that gave statistically significant results. In 9 trials with a total of 139 subjects, mean difference could be calculated; weighted for study size, it was 29% range 24-74%. Willingness to drive was significantly greater in 4 of 6 studies including a total of 105 subjects; weighted mean difference increased by 207% range 79-300%. By contrast, measure of driving ability in three groups of a total of 200 trials in 57 subjects showed worse performance by a weighted mean of 96% range 3-566%. In three trials that tested inhibitory control (cued go or no-go response times), weighted mean performance was 30% range 14-65% worse on the descending limb.
Conclusions: The "Mellanby effect" has been demonstrated for subjective intoxication and willingness to drive, both of which are more affected at a stated ethanol concentration when BAC is rising than at the same concentration when BAC is falling. By contrast, objective measures of skills necessary for safe driving, such as response to inhibitory cues and skills measured on driving simulators, were generally worse on the descending part of the BAC-time curve for the same BAC.
Workplace Lead Exposure Holland, Michael G.; Cawthon, David
Journal of occupational and environmental medicine,
2016-December, Letnik:
58, Številka:
12
Journal Article
Increasing body mass index (BMI) is a known risk factor for autologous microsurgical breast reconstruction. No prior studies have stratified outcomes across BMI ranges or defined the BMI at which ...complication rates dramatically increase.
The authors performed a retrospective chart review of all patients who underwent abdominally based autologous free flap breast reconstruction at their institution between 2004 and 2021. Clinical, surgical, and outcomes data were collected. Patients were stratified into five BMI categories: 25, 25.01 to 30, 30.01 to 35, 35.01 to 40, and greater than 40 kg/m 2 . Complication rates were analyzed across these groups, and a receiver-operating characteristic analysis was used to determine an optimal BMI cutoff point.
A total of 365 patients (545 breasts) were included in this study. The rates of several breast complications significantly increased with increasing BMI at distinct levels, including any breast complication (BMI >30 kg/m 2 ), unplanned reoperation (BMI >35 kg/m 2 ), fat necrosis (BMI >40 kg/m 2 ), wound breakdown requiring re-operation (BMI >35 kg/m 2 ), any infection (BMI >30 kg/m 2 ), infection requiring oral antibiotics (BMI >25 kg/m 2 ), infection requiring intravenous antibiotics (BMI >35 kg/m 2 ), and mastectomy flap necrosis (BMI >35 kg/m 2 ). The rates of many abdominal complications significantly increased with increasing BMI at distinct levels as well, including delayed wound healing (BMI >30 kg/m 2 ), wound breakdown requiring re-operation (BMI >40 kg/m 2 ), any infection (BMI >25 kg/m 2 ), and infection requiring oral antibiotics (BMI >25 kg/m 2 ). Optimal BMI cutoffs of 32.7 and 30.0 kg/m 2 were determined to minimize the occurrence of any breast complication and any abdomen complication, respectively.
Preoperative weight loss has great potential to alleviate surgical risk in overweight and obese patients pursuing autologous breast reconstruction. The authors' results quantify the risk reduction based on a patient's preoperative BMI.
Risk, II.
Background
People with haemophilia A and inhibitors (PwHi) suffer more orthopaedic complications, bleeding and pain than those without inhibitors. The advent of emicizumab as a prophylactic treatment ...has led to a reduction in bleed frequency and a significant improvement in overall quality of life. No research to date has examined the nature of this improvement on treated individuals and their families.
Aims
The Emi & Me study aims to capture the real‐life experience of using emicizumab for PwHi and their families.
Methods
Participants were recruited through treatment centres, social media and by word of mouth. Each participant and a family member, if available, took part in a semistructured qualitative interview. All interviews were recorded, transcribed verbatim and analysed thematically. All elements of the study were reviewed by local statutory authorities and informed consent was sought from all participants.
Results
Fifteen PwHi, mean age 27.2 years (range 8–63 years), most with a family member, participated in a single qualitative interview online (n = 13), by telephone (n = 1) or in person (n = 1). Mean time on emicizumab was 2.26 years (range 1–5 years). Six major themes emerged: bleeds; pain; treatment burden; control; freedom (for both PwHi and family members) and missed potential. Emicizumab prophylaxis has delivered significant improvements in the lives of the participants. Despite these improvements, some participants felt that their pre‐existing physical disabilities and the lack of physiotherapy provision had prevented them achieving similar improvements in their functional ability.
Conclusion
This study shows that in reducing bleeds, pain and treatment burden, emicizumab had given PwHi greater control over their condition, allowing a sense of freedom they had not experienced with factor VIII or bypassing agent prophylaxis. However, for emicizumab to be truly effective, there is a need to ensure the continued availability and accessibility of robust multidisciplinary support services. Without this, it is unlikely that PwHi will realize the life‐changing potential offered either by emicizumab or any other novel treatment approach.
Patient or Public Contribution
A patient participant (who did not wish to be included as an author of the paper) was involved in the design of the study protocol and interview guide.
While the mechanisms that underpin maturation, capacitation, and sperm–egg interactions remain elusive it is known that these essential fertilisation events are driven by the protein complement of ...the sperm surface. Understanding these processes is critical to the regulation of animal reproduction, but few studies have attempted to define the full repertoire of sperm surface proteins in animals of agricultural importance. Recent developments in proteomics technologies, subcellular fractionation, and optimised solubilisation strategies have enhanced the potential for the comprehensive characterisation of the sperm surface proteome. Here we report the identification of 419 proteins from a mature bull sperm plasma membrane fraction. Protein domain enrichment analyses indicate that 67% of all the proteins identified may be membrane associated. A large number of the proteins identified are conserved between mammalian species and are reported to play key roles in sperm–egg communication, capacitation and fertility. The major functional pathways identified were related to protein catabolism (26S proteasome complex), chaperonin‐containing TCP‐1 (CCT) complex and fundamental metabolic processes such as glycolysis and energy production. We have also identified 118 predicted transmembrane proteins, some of which are implicated in cell adhesion, acrosomal exocytosis, vesicle transport and immunity and fertilisation events, while others have not been reported in mammalian LC‐MS‐derived sperm proteomes to date. Comparative proteomics and functional network analyses of these proteins expand our system's level of understanding of the bull sperm proteome and provide important clues toward finding the essential conserved function of these proteins.
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