Three Decades Single Center Experience of Airway Complications After Lung Transplantation.

Post lung transplantation airway complications like necrosis, stenosis, malacia and dehiscence cause significant morbidity, and are most likely caused by post-operative hypo perfusion of the anastomosis. Treatment can be challenging, and airway stent placement can be necessary in severe cases. Risk factors for development of airway complications vary between studies. In this single center retrospective cohort study, all lung transplant recipients between November 1990 and September 2020 were analyzed and clinically relevant airway complications of the anastomosis or distal airways were identified and scored according to the ISHLT grading system. We studied potential risk factors for development of airway complications and evaluated the impact on survival. The treatment modalities were described. In 651 patients with 1,191 airway anastomoses, 63 patients developed 76 clinically relevant airway complications of the airway anastomoses or distal airways leading to an incidence of 6.4% of all anastomoses, mainly consisting of airway stenosis (67%). Development of airway complications significantly affects median survival in post lung transplant patients compared to patients without airway complication (101 months versus 136 months, p = 0.044). No significant risk factors for development of airway complication could be identified. Previously described risk factors could not be confirmed. Airway stents were required in 55% of the affected patients. Median survival is impaired by airway complications after lung transplantation. In our cohort, no significant risk factors for the development of airway complications could be identified.

Tremor, Daily Functioning, and Health-Related Quality of Life in Solid Organ Transplant Recipients.

Solid organ transplant recipients (SOTR) frequently report tremor. Data concerning tremor-related impairment and its potential impact on health-related quality of life (HRQoL) are lacking. This cross-sectional study assesses impact of tremor on activities of daily living and HRQoL using validated questionnaires among SOTR enrolled in the TransplantLines Biobank and Cohort Study. We included 689 SOTR (38.5% female, mean [±SD] age 58 [±14] years) at median [interquartile range] 3 [1-9] years after transplantation, of which 287 (41.7%) reported mild or severe tremor. In multinomial logistic regression analyses, whole blood tacrolimus trough concentration was an independent determinant of mild tremor (OR per µg/L increase: 1.11, 95% CI: 1.02 to 1.21, p = 0.019). Furthermore, in linear regression analyses, severe tremor was strongly and independently associated with lower physical and mental HRQoL (ß = -16.10, 95% CI: -22.23 to -9.98, p < 0.001 and ß = -12.68, 95% CI: -18.23 to -7.14, p < 0.001 resp.). SOTR frequently report tremor-related impairment of activities of daily living. Tacrolimus trough concentrations appeared as a main determinant of tremor among SOTR. The strong and independent association of tremor-related impairment with lower HRQoL warrants further studies into the effects of tacrolimus on tremor. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT03272841.

High resolution front-side visualization of charge stored in EEPROM with scanning nonlinear dielectric microscopy (SNDM).

By exposing floating gates of EEPROM memory cells with frontside sample preparation, scanning nonlinear dielectric microscopy (SNDM) succeeded in reading back the data stored in the memory cells with a 250 nm node size. At an optimized voltage bias of AC = 3 V and DC = 1 V, a clear signal contrast between programmed and erased cells is obtained. The high resolution SNDM signal reveals the details of bowling-pin shape structure of memory cells, providing high confidence in data assignment during forensic applications. Such high resolution also makes SNDM a promising technique for newer generation devices with smaller node size.

Attitudes towards risk-reducing early salpingectomy with delayed oophorectomy for ovarian cancer prevention: a cohort study.

OBJECTIVE: To determine risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk. DESIGN: Multicentre, cohort, questionnaire study (IRSCTN:12310993). SETTING: United Kingdom (UK). POPULATION: UK women without OC ≥18 years, at increased OC risk, with/without previous RRSO, ascertained through specialist familial cancer/genetic clinics and BRCA support groups. METHODS: Participants completed a 39-item questionnaire. Baseline characteristics were described using descriptive statistics. Logistic/linear regression models analysed the impact of variables on RRESDO acceptability and health outcomes. MAIN OUTCOMES: RRESDO acceptability, menopausal sequelae, satisfaction/regret. RESULTS: In all, 346 of 683 participants underwent risk-reducing salpingo-oophorectomy (RRSO). Of premenopausal women who had not undergone RRSO, 69.1% (181/262) found it acceptable to participate in a research study offering RRESDO. Premenopausal women concerned about sexual dysfunction were more likely to find RRESDO acceptable (odds ratio [OR] = 2.9, 95% CI 1.2-7.7, P = 0.025). Women experiencing sexual dysfunction after premenopausal RRSO were more likely to find RRESDO acceptable in retrospect (OR = 5.3, 95% CI 1.2-27.5, P < 0.031). In all, 88.8% (143/161) premenopausal and 95.2% (80/84) postmenopausal women who underwent RRSO, respectively, were satisfied with their decision, whereas 9.4% (15/160) premenopausal and 1.2% (1/81) postmenopausal women who underwent RRSO regretted their decision. HRT uptake in premenopausal individuals without breast cancer (BC) was 74.1% (80/108). HRT use did not significantly affect satisfaction/regret levels but did reduce symptoms of vaginal dryness (OR = 0.4, 95% CI 0.2-0.9, P = 0.025). CONCLUSION: Data show high RRESDO acceptability, particularly in women concerned about sexual dysfunction. Although RRSO satisfaction remains high, regret rates are much higher for premenopausal women than for postmenopausal women. HRT use following premenopausal RRSO does not increase satisfaction but does reduce vaginal dryness. TWEETABLE ABSTRACT: RRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction.

A single-centre experience and literature review of Flow Re-Directional Endoluminal Device (FRED) in endovascular treatment of intracranial aneurysms.

AIM: To present initial single-centre experience with the Flow Re-Direction Endoluminal Device, FRED. MATERIALS AND METHODS: This was a retrospective study. All patients treated with FRED from October 2015 to April 2017 were included in the study. Details of the aneurysms, complications as well as follow-up results were recorded. A PubMed search was performed using the keywords "Flow Re-Direction Endoluminal Device", "FRED", "flow diverter", "FD", "FD Stent", "flow re-direction" and "flow redirection" and the results were reviewed and compared to the present authors. RESULTS: A total of 21 patients with 25 aneurysms were analysed. No patient was lost to follow-up. At 6 months follow-up, 17 aneurysms (68%) were completely occluded, five had reduced flow, two had persistent flow and the remaining one showed increased flow. Two aneurysms from the reduced flow at 6 months had achieved complete occlusion at 1 year, raising the complete occlusion rate to 76%. Overall, 22/25 (88%) aneurysms were either occluded completely or had reduced flow at 1 year. The appearances of the other aneurysms were stable in subsequent follow-ups. Three complications were recorded (one haemorrhagic, two occlusive/thromboembolic). There was no mortality in the present study. The occlusion rate at University Hospital of Wales as well as the complication rate was comparable to other centres on published data. CONCLUSION: FRED is a safe and effective flow diverter, which can be used to treat complex aneurysms that would have been of higher risk and for which for conventional coiling would be ineffective or unsuitable.

[A multicenter randomized controlled study of bismuth-containing quadruple therapy followed by Jing-Hua-Wei-Kang in the treatment of patients newly diagnosed with Helicobacter pylori infection and dyspepsia].

Objective: To investigate the Helicobacter pylori (H. pylori) eradication rate and improvement of dyspepsia in patients who were newly diagnosed with H. pylori infection and dyspepsia and treated by bismuth-containing quadruple therapy followed by Jing-Hua-Wei-Kang(JHWK). Methods: Patients who were newly diagnosed with dyspepsia and H. pylori infection and treated in 16 medical centers in China between December 1, 2017 and September 30, 2019 were randomly divided into two groups. The experimental group received bismuth-containing quadruple therapy (esomeprazole+amoxicillin+furazolidone+colloidal bismuth pectin capsule, 14 days), followed by JHWK (30 days), and the course of treatment was 44 days in total. In the control group, the administration regimen was bismuth-containing quadruple therapy (esomeprazole+amoxicillin+furazolidone+colloidal bismuth pectin capsule, 14 days). The main outcome measure was H. pylori eradication rate, while the secondary outcome measures were dyspepsia symptom changes and adverse events during the treatment and the 1st month after treatment. Results: A total of 1 054 patients were included in the study. There were 522 cases enrolled in the experimental group, including 224(42.91%) men and 298(57.09%) women, and the age was 53(26, 73) years old; 532 cases enrolled in the control group, including 221(41.54%) men and 311(58.46%) women, and the age was 46(22, 71) years old. Based on PP analysis, it was found that the H. pylori eradication rate in the experimental group was significantly higher than those in the control group (93.85% vs 87.88%, P=0.001). In the group of all enrolled patients, the symptom dyspepsia after H. pylori eradication was significantly improved compared with that before treatment [4(4, 7) vs 15(10, 22), P<0.001], so was the superior and middle abdominal pain [1(1, 4) vs 4(1, 8), P<0.001], the postprandial fullness [1(1, 4) vs 4(4, 9), P<0.001], the early satiety [1(1, 1) vs 4(1, 4), P<0.001], and the heartburn [1(1, 1) vs 1(1, 4), P<0.001]. The symptom dyspepsia after treatment was significantly improved compared with that before treatment in the experimental, the control groups, the successful and the unsuccessful H. pylori eradication groups. The superior and middle abdominal pain after treatment was signifcantly improved than that before treatment [1(1, 2) vs 1(1, 4), P<0.001], so were the postprandial fullness [1(1, 3) vs 1(1, 4), P=0.002] and the dyspepsia[4(4, 7) VS 7(4, 10), P<0.001]. There was no statistically significant difference in the incidence of adverse events between the experimental group and the control group (1.34% vs 0.38%, P=0.09). Conclusions: Compared with bismuth-containing quadruple therapy, bismuth-containing quadruple therapy followed by JHWK significantly improves the H. pylori eradication rate without increasing the incidence of adverse events. H. pylori eradication therapy can improve symptoms of patients with H. pylori infection and dyspepsia.

The role of acute internal medicine service in handling burden of medical access block in a tertiary hospital, Hospital Melaka experience.

INTRODUCTION: Access block is a major problem faced by most hospitals. It has led to congestions in emergency departments (ED) leading to sub-optimal or delayed treatment. Inevitably the spotlight falls on medical department, being accountable for the highest proportion of access block in ED. MATERIALS AND METHODS: This is a retrospective study looking at data collected during office hours on 79 working days, excluding weekends and public holidays in Hospital Melaka, Malaysia. Details on all medical access block cases that were reviewed were recorded including their locations, diagnosis, disposition decisions and if they received specialist input at the time of their initial assessment by the medical team in ED. The aim is to revolutionise patient admission flow by offering early specialist care with rapid assessment, investigation and treatment. Hence, improving the overall treatment efficiency and reduce medical access block. RESULTS: There were 1321 admissions. A total of 82% of the patients were admitted to the medical wards while 13% of them were given acute treatment in ED and discharged home with appropriate follow ups. We managed to resolve 18% of medical access block by re-triaging our cases and offering timely acute medical treatment. Nearly 90% of patients received first hand medical specialist input during the initial assessment by the Acute Internal Medicine (AIM) team in ED. CONCLUSION: The significant resolution in medical access block with active screening, re-triaging and management of patients by the AIM team allows a more optimal hospital bed management. Patients also receive timely access to medical intervention with specialist care and stable patients can benefit from early supported discharge.

A case of intracranial molluscum contagiosum virus infection diagnosed by metagenomic sequencing of cerebrospinal fluid.

Molluscum contagiosum is a common, self-limiting infectious disease of the skin caused by molluscum contagiosum virus (MCV). The disease primarily affects children, sexually active adults, and immunocompromised individuals. Transmission of the virus occurs by direct skin contact. Therefore, the virus is usually detected in the skin and genitals of patients. However, the diagnosis of intracranial infection by the virus is difficult if the skin/mucosa lessons are atypical or absent, and the presence of the virus in the cerebrospinal fluid has not been reported. We report a very rare case of intracranial infection by molluscum contagiosum virus. A 25-year-old girl was admitted to our hospital due to severe headache but no fever or other symptoms. Upon examination, some small flesh-colored flattened papules on both arms were noticed. Blood tests showed slightly reduced levels of CD3 and CD4 T lymphocytes. Three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and head magnetic resonance (MR) were both normal. Lumbar puncture was performed, and metagenomic sequencing was applied to the spinal fluid. The unique sequences of the molluscum contagiosum virus were identified in the fluid. The patient was then diagnosed with intracranial molluscum contagiosum virus infection. No special treatment was given. The headache gradually disappeared, and the patient was discharged. During our quarterly follow-up, the girl appeared normal, and her skin lesions disappeared. However, her CD3 and CD4 T lymphocyte counts were still slightly lower than the normal level. Our case shows that the application of metagenomic sequencing to cerebrospinal fluid is a sensitive and powerful means to detect pathogens causing intracranial infection. Keywords: Molluscum contagiosum; intracranial infection; metagenomics sequencing.

[Therapeutic effect of Jin Long capsule combined with neoadjuvant chemotherapy on invasive breast cancer and the expression change of multidrug resistance proteins].

Objective: To investigate the therapeutic effect of Jin Long Capsule (JLC) combined with neoadjuvant chemotherapy on the invasive breast cancer, and to explore the mechanism of JLC in inhibiting multidrug resistance of breast cancer. Methods: 200 patients were divided into experimental group and control group (100 cases per group). The control group used TEC regimen for neoadjuvant chemotherapy. And the experimental group was treated with TEC regimen combined with oral JLC. According to the Miller & Payne grading system (MP), the efficacy of neoadjuvant chemotherapy was evaluated based on histopathological changes of breast cancer after neoadjuvant chemotherapy. Adverse effect was evaluated according to the classification criteria of the National Cancer Institute of the United States-The Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The expression of P-glycoprotein (P-gp), glutathione thiol transferase (GST)-π and topoisomerase Ⅱα (TopoⅡα) in breast cancer tissues before and after neoadjuvant chemotherapy were detected by immunohistochemical staining. Results: There were 83 effective cases (83%) in the experimental group, which was higher than that in the control group (65.0%, P<0.05). The incidence of leukopenia, gastrointestinal reactions and alopecia in grade 3 to 4 of the experimental group were lower than those of the control group (all P<0.05). The positive rates of P-gp, GST-π and TopoⅡα expression in the control group were 65.0% (65/100), 61.0% (61/100) and 69.0% (69/100), respectively, and they were 80.6% (75/93), 78.5% (73/93) and 37.6% (35/93) after chemotherapy. The positive rates of P-gp and GST-π expression were significantly higher than those before chemotherapy (both P<0.05), whereas the positive rate of TopoⅡα expression was significantly lower than that before chemotherapy (P<0.05). In the experimental group, the positive rates of P-gp, GST-π and TopoⅡα expression before chemotherapy were 62.0% (62/100), 63.0% (63/100) and 69.0% (69/100), respectively, while after chemotherapy, they were 68.2% (60/88), 67.0% (59/88) and 63.6% (56/88). There was no significant difference in the positive rates and expression intensity of P-gp, GST-π and TopoⅡα before and after the chemotherapy (P>0.05). Conclusion: Jin Long Capsule (JLC) can inhibit multidrug resistance, improve the efficacy of neoadjuvant chemotherapy, and reduce adverse reactions of breast cancer.

Tunable room-temperature magnetic skyrmions in Ir/Fe/Co/Pt multilayers.

Magnetic skyrmions are nanoscale topological spin structures offering great promise for next-generation information storage technologies. The recent discovery of sub-100-nm room-temperature (RT) skyrmions in several multilayer films has triggered vigorous efforts to modulate their physical properties for their use in devices. Here we present a tunable RT skyrmion platform based on multilayer stacks of Ir/Fe/Co/Pt, which we study using X-ray microscopy, magnetic force microscopy and Hall transport techniques. By varying the ferromagnetic layer composition, we can tailor the magnetic interactions governing skyrmion properties, thereby tuning their thermodynamic stability parameter by an order of magnitude. The skyrmions exhibit a smooth crossover between isolated (metastable) and disordered lattice configurations across samples, while their size and density can be tuned by factors of two and ten, respectively. We thus establish a platform for investigating functional sub-50-nm RT skyrmions, pointing towards the development of skyrmion-based memory devices.

Subunit Vaccines Consisting of Antigens from Dormant and Replicating Bacteria Show Promising Therapeutic Effect against Mycobacterium Bovis BCG Latent Infection.

To screen effective antigens as therapeutic subunit vaccines against Mycobacterium latent infection, we did bioinformatics analysis and literature review to identify effective antigens and evaluated the immunogenicity of five antigens highly expressed in dormant bacteria, which included Rv2031c (HspX), Rv2626c (Hrp1), Rv2007c (FdxA), Rv1738 and Rv3130c. Then, several fusion proteins such as Rv2007c-Rv2626c (F6), Rv2031c-Rv1738-Rv1733c (H83), ESAT6-Rv1738-Rv2626c (LT40), ESAT6-Ag85B-MPT64<190-198> -Mtb8.4 (EAMM), and EAMM-Rv2626c (LT70) were constructed and their therapeutic effects were evaluated in pulmonary Mycobacterium bovis Bacilli Calmette-Guérin (BCG) - latently infected rabbit or mouse models. The results showed that EAMM and F6 plus H83 had therapeutic effect against BCG latent infection in the rabbit model, respectively, and that the combination of EAMM with F6 plus H83 significantly reduced the bacterial load. In addition, the fusion proteins LT40 and LT70 consisting of multistage antigens showed promising therapeutic effects in the mouse model. We conclude that subunit vaccines consisting of both latency and replicating-associated antigens show promising therapeutic effects in BCG latent infection animal models.

Association of imaging abnormalities of the subcallosal septal area with Alzheimer's disease and mild cognitive impairment.

AIM: To evaluate the use the distance between the adjacent septal nuclei as a surrogate marker of septal area atrophy seen in Alzheimer's disease (AD). MATERIALS & METHODS: Interseptal distance (ISD) was measured, blind to clinical details, in 250 patients who underwent computed tomography (CT) of the brain at University Hospital of Wales. Clinical details including memory problem history were retrieved. An ISD cut-off value that discriminated those with and without memory symptoms was sought. ISD measurements were also made in 20 AD patients. To test both the method and the defined cut-off, measurements were then made in an independent cohort of 21 mild cognitive impairment (MCI) patients and 45 age-matched healthy controls, in a randomised and blinded fashion. RESULTS: ISD measurement was achieved in all patients. In 28 patients with memory symptoms, the mean ISD was 5.9 mm compared with 2.3 mm in those without overt symptoms (p=0.001). The optimum ISD cut-off value was 4 mm (sensitivity 85.7% and specificity 85.8%). All AD patients had an ISD of >4 mm (mean ISD= 6.1 mm). The mean ISD for MCI patients was 3.84 mm compared with 2.18 mm in age-matched healthy controls (p=0.001). Using a 4 mm cut-off correctly categorised 10 mild cognitive impairment patients (47.6%) and 38 healthy controls (84.4%). CONCLUSION: ISD is a simple and reliable surrogate measurement for septal area atrophy, applicable to CT and magnetic resonance imaging (MRI). It can be used to help select patients for further investigation.

Primary Cutaneous T Cell Lymphoma (Gamma Delta subtype).

Primary cutaneous T-cell lymphoma gamma-delta subtype is an extremely rare entity of all the cutaneous T-cell lymphomas. Our case provides an insight on clinical behavior and treatment response with feasible effective combination chemotherapy. We believe this will be of great interest to clinicians when facing this difficult clinical entity. We present a case of a 66-year-old Malay man with a threeweek history of rapidly growing skin nodules and plaques which spread throughout his body. He was commenced on combination chemotherapy gemcitabine, etoposide, and carboplatin with near complete remission on completion of second cycle but he defaulted. He relapsed within a month and he progressed despite treatment with the same regime. He was salvaged with fludarabine, cytarabine, and vinblastine combination chemotherapy but progressed with brain metastasis and died. However, more investigations and studies need to be done in this relatively unknown rare entity. A rare lymphoma registry might be of help to better understand and treat similar conditions.

Right ventricular diastolic impairment in patients with pulmonary arterial hypertension.

BACKGROUND: The role of right ventricular (RV) diastolic stiffness in pulmonary arterial hypertension (PAH) is not well established. Therefore, we investigated the presence and possible underlying mechanisms of RV diastolic stiffness in PAH patients. METHODS AND RESULTS: Single-beat RV pressure-volume analyses were performed in 21 PAH patients and 7 control subjects to study RV diastolic stiffness. Data are presented as mean ± SEM. RV diastolic stiffness (ß) was significantly increased in PAH patients (PAH, 0.050 ± 0.005 versus control, 0.029 ± 0.003; P<0.05) and was closely associated with disease severity. Subsequently, we searched for possible underlying mechanisms using RV tissue of PAH patients undergoing heart/lung transplantation and nonfailing donors. Histological analyses revealed increased cardiomyocyte cross-sectional areas (PAH, 453 ± 31 µm² versus control, 218 ± 21 µm²; P<0.001), indicating RV hypertrophy. In addition, the amount of RV fibrosis was enhanced in PAH tissue (PAH, 9.6 ± 0.7% versus control, 7.2 ± 0.6%; P<0.01). To investigate the contribution of stiffening of the sarcomere (the contractile apparatus of RV cardiomyocytes) to RV diastolic stiffness, we isolated and membrane-permeabilized single RV cardiomyocytes. Passive tension at different sarcomere lengths was significantly higher in PAH patients compared with control subjects (>200%; Pinteraction <0.001), indicating stiffening of RV sarcomeres. An important regulator of sarcomeric stiffening is the sarcomeric protein titin. Therefore, we investigated titin isoform composition and phosphorylation. No alterations were observed in titin isoform composition (N2BA/N2B ratio: PAH, 0.78 ± 0.07 versus control, 0.91 ± 0.08), but titin phosphorylation in RV tissue of PAH patients was significantly reduced (PAH, 0.16 ± 0.01 arbitrary units versus control, 0.20 ± 0.01 arbitrary units; P<0.05). CONCLUSIONS: RV diastolic stiffness is significantly increased in PAH patients, with important contributions from increased collagen and intrinsic stiffening of the RV cardiomyocyte sarcomeres.

Is routine gastrointestinal endoscopy required in every woman with mucinous ovarian cancer? An analysis of survival rates and metastatic tumours in a cancer centre.

INTRODUCTION: Mucinous ovarian cancer (MOC) represents a rare entity of ovarian malignant neoplasms. The true incidence could be as low as 3% of all ovarian cancers. The aim of this study is to compare and understand the clinicopathological characteristics of patients with mucinous ovarian cancer, report on the survival rates and evaluate the role of gastrointestinal (GI) endoscopy as part of the peri-operative investigations and the impact it has on the survival rates. METHODOLOGY: This is a retrospective data collection on patients with MOC operated in Nottingham gynaecological oncology centre over a 10-year period. Data were analysed using SPSS software. RESULTS: 43 cases were included in the final analysis. The median maximal tumour diameter was 180 mm. 32 (74.5 %) and 11 (25.5 %) women presented with unilateral and bilateral tumours respectively. 30 patients (69.7 %) presented with stage 1 disease, 1 (2.3 %) presented with stage 2 disease, 7 women (16.4 %) had stage 3 disease and 1 woman (11.6 %) had stage 4 disease. 41 women had staging surgical procedures and 2 women had limited surgery due to poor performance status. After final histology, 5 cases found to have metastatic disease to the ovary rather than primary MOC. 14 women had GI endoscopy as part of their investigation. The total estimated cost of the endoscopies that have been performed is £5635. Primary GI cancer was diagnosed in 1 case during the endoscopy (1 case of gastric cancer). The 5-year overall survival of the women included in this study is 62.8 %. The 5-year overall survival of the women in the endoscopy and non-endoscopy groups was 60 % and 64.3 % respectively (p-value: 0.767). CONCLUSION: The findings of this study show that the survival rates of patients treated for mucinous ovarian cancer in our centre are similar to other published studies. Our findings do not support the routine use of GI endoscopy in the peri-operative investigations of every patient with MOC due to the non-statistically significant difference in the overall survival.

Pyruvate carboxylase deficiency type C; variable presentation and beneficial effect of triheptanoin.

Pyruvate carboxylase is a mitochondrial enzyme essential for the tricarboxylic acid cycle (TCA), gluconeogenesis and fatty-acid synthesis. Pyruvate carboxylase deficiency (PCD) mostly presents with life-limiting encephalopathy (types A/B). A milder type C presentation is rare, with a comparatively favourable prognosis. Therapies remain essentially supportive. Triheptanoin is an odd-chain triglyceride, with the potential to replenish TCA intermediates (anaplerosis), and its metabolites cross the blood-brain-barrier. Outcomes of triheptanoin treatment in PCD types A/B have been disappointing, but have not been reported in type C. Here, we present two new patients with PCD type C, and report the response to treatment with triheptanoin in one. Patient 1 (P1) presented with neonatal-onset lactic acidosis and recurrent symptomatic lactic acidosis following exercise and during illnesses, with frequent hospitalisations. Speech development was delayed. MRI-brain showed delayed cerebral myelination. Patient 2 (P2) presented with episodic ketoacidosis, hyperlactataemia and hypoglycaemia at 2 years of age, with gross motor delay and mild global volume loss on MRI brain. Treatment with triheptanoin was commenced in P1 at 3 years of age with up-titration to 35 mL/day (25% of daily energy intake) over 6 months, due to transient diarrhoea. Dietary long-chain triglycerides were restricted, with fat-soluble vitamin supplementation. Subsequently, hospitalisations during intercurrent illnesses decreased, post-exertional hyperlactataemia resolved and exercise tolerance improved. Continued developmental progress was observed, and repeat MRI 18 months after initiation showed improved myelination. Triheptanoin was well-tolerated and appeared efficacious during 2 years' follow-up, and has potential to restore energy homeostasis and myelin synthesis in PCD type C.

The gut microbiome in end-stage lung disease and lung transplantation.

Gut dysbiosis has been associated with impaired outcomes in liver and kidney transplant recipients, but the gut microbiome of lung transplant recipients has not been extensively explored. We assessed the gut microbiome in 64 fecal samples from end-stage lung disease patients before transplantation and 219 samples from lung transplant recipients after transplantation using metagenomic sequencing. To identify dysbiotic microbial signatures, we analyzed 243 fecal samples from age-, sex-, and BMI-matched healthy controls. By unsupervised clustering, we identified five groups of lung transplant recipients using different combinations of immunosuppressants and antibiotics and analyzed them in relation to the gut microbiome. Finally, we investigated the gut microbiome of lung transplant recipients in different chronic lung allograft dysfunction (CLAD) stages and longitudinal gut microbiome changes after transplantation. We found 108 species (58.1%) in end-stage lung disease patients and 139 species (74.7%) in lung transplant recipients that were differentially abundant compared with healthy controls, with several species exhibiting sharp longitudinal increases from before to after transplantation. Different combinations of immunosuppressants and antibiotics were associated with specific gut microbial signatures. We found that the gut microbiome of lung transplant recipients in CLAD stage 0 was more similar to healthy controls compared to those in CLAD stage 1. Finally, the gut microbial diversity of lung transplant recipients remained lower than the average gut microbial diversity of healthy controls up to more than 20 years post-transplantation. Gut dysbiosis, already present before lung transplantation was exacerbated following lung transplantation.IMPORTANCEThis study provides extensive insights into the gut microbiome of end-stage lung disease patients and lung transplant recipients, which warrants further investigation before the gut microbiome can be used for microbiome-targeted interventions that could improve the outcome of lung transplantation.

Broadband and efficient plasmonic control in the near-infrared and visible via strong interference of surface plasmon polaritons.

Broadband and tunable control of surface plasmon polaritons in the near-infrared and visible spectrum is demonstrated theoretically and numerically with a pair of phased nanoslits. We establish, with simulations supported by a coupled wave model, that by dividing the incident power equally between two input channels, the maximum plasmon intensity deliverable to either side of the nanoslit pair is twice that for an isolated slit. For a broadband source, a compact device with nanoslit separation of the order of a tenth of the wavelength is shown to steer nearly all the generated plasmons to one side for the same phase delay, thereby achieving a broadband unidirectional plasmon launcher. The reported effect can be applied to the design of ultra-broadband and efficient tunable plasmonic devices.

Dynamic beam steering from a subwavelength slit by selective excitation of guided modes.

Dynamic control of the direction of radiation of the light emanating from a subwavelength slit carved out of a thin metal film is experimentally demonstrated. This is achieved by selective excitation of the individual guided modes in the slit by setting the phase of three coherent laser beams. By changing the voltage across a piezoelement, we obtain unprecedented directional steering, without relying on any mechanical alignment of optical elements. The angular range over which this maximum can be swept is determined by the intensity setting of one of the incident beams. Through simulations, we show that this method can also be applied to steer the radiation from a square hole in two independent directions. Our method can be applied to create a directional nanoemitter which can selectively address one or more detectors, or as an optical switch in photonic circuits.