Raman Interferometry between Autoionizing States to Probe Ultrafast Wave-Packet Dynamics with High Spectral Resolution.

Photoelectron interferometry with femtosecond and attosecond light pulses is a powerful probe of the fast electron wave-packet dynamics, albeit it has practical limitations on the energy resolution. We show that one can simultaneously obtain both high temporal and spectral resolution by stimulating Raman interferences with one light pulse and monitoring the modification of the electron yield in a separate step. Applying this spectroscopic approach to the autoionizing states of argon, we experimentally resolved its electronic composition and time evolution in exquisite detail. Theoretical calculations show remarkable agreement with the observations and shed light on the light-matter interaction parameters. Using appropriate Raman probing and delayed detection steps, this technique enables highly sensitive probing and control of electron dynamics in complex systems.

Outpatient healthcare utilization among incident cases of systemic sclerosis: results from a population-based US cohort (1988-2016).

OBJECTIVE: Systemic sclerosis (SSc) is a complex, heterogeneous connective tissue disease with multiorgan dysfunction. This study aimed to compare healthcare utilization among incident cases of SSc versus age- and gender-matched comparators. METHOD: A population-based cohort of physician-diagnosed patients with SSc in Olmsted County, MN, USA, from 1 January 1988 to 31 December 2016 was assembled. A 2:1 cohort of age- and gender-matched non-SSc subjects was randomly selected for comparison. Patients were followed until death, migration from Olmsted County, or 31 December 2017. Outpatient utilization data were obtained beginning 12 months before the SSc incidence/index date and compared using negative binomial and multinomial models. Services were summarized as visit-days to avoid overestimation of services provided. RESULTS: The study included 69 incident SSc cases and 138 non-SSc comparators (mean ± sd age 57 ± 16 years at diagnosis/index, 90% female). Patients with SSc had higher utilization of outpatient physician, laboratory, and combined radiology visit-days annually for the year before and for each of the first 5 years after diagnosis than comparators. Among patients with SSc, healthcare utilization was highest during the year of SSc diagnosis. Rate ratios comparing utilization in patients with and without SSc ranged from 1.8 to 3.0 for all comparisons. CONCLUSION: Higher utilization of outpatient physician, laboratory, and radiology visit-days was observed among patients with SSc compared to non-SSc subjects throughout 5 years of disease duration, indicating high and continued care needs in this patient population. The highest utilization of services among SSc patients occurred during the year of SSc diagnosis.

[Pharmacobezoar in a woman with a clomipramine intoxication]. / Een bezoar bij een vrouw met clomipramine-intoxicatie.

BACKGROUND: Medicines with controlled release can cause a rare phenomenon, known as pharmacobezoar, following overdose of these medications. CASE DESCRIPTION: A case of a 56-year-old women with severe clomipramine intoxication is described. X-ray of the abdomen showed a cluster of tablets in the caecum. Lab results showed severe plasma concentration of clomipramine. Patient was treated with active coal and remained stable. CONCLUSION: It is important to be aware of the presence of pharmacobezoar in intoxication with controlled release medicines. The formation of pharmacobezoar can lead to unpredictable duration of intoxication.

Autoionizing Polaritons in Attosecond Atomic Ionization.

Light-induced states and Autler-Townes splitting of laser-coupled states are common features in the photoionization spectra of laser-dressed atoms. The entangled light-matter character of metastable Autler-Townes multiplets, which makes them autoionizing polaritons, however, is still largely unexplored. We employ attosecond transient-absorption spectroscopy in argon to study the formation of polariton multiplets between the 3s^{-1}4p and several light-induced states. We measure a controllable stabilization of the polaritons against ionization, in excellent agreement with ab initio theory. Using an extension of the Jaynes-Cummings model to autoionizing states, we show that this stabilization is due to the destructive interference between the Auger decay and the radiative ionization of the polaritonic components. These results give new insights into the optical control of electronic structure in the continuum and unlock the door to applications of radiative stabilization in metastable polyelectronic systems.

Clinical outcomes after faecal microbiota transplant by retention enema in both immunocompetent and immunocompromised patients with recurrent Clostridioides difficile infections at an academic medical centre.

BACKGROUND: Recurrent Clostridioides difficile infection (CDI) is one of the most common and challenging infections to treat in healthcare facilities. Faecal microbiota transplantation (FMT) is recommended as a definitive treatment option. METHODS: We performed a retrospective review of 50 patients from January 2015 to December 2019 who underwent FMT for recurrent CDI. Primary outcome was recurrence of CDI within 12-weeks of FMT and secondary outcomes were the need for repeat FMT, serious adverse outcomes related to FMT and all-cause mortality. RESULTS: Fifty charts were reviewed, of which 47 cases comprising 17 immunocompromised patients treated with FMT via retention enema were included in the study. The majority of the patients had ≥3 recurrent CDIs (62%). Nine (19%) patients failed to respond to the first FMT and five underwent repeat FMT within four to 12 weeks. The cure rate was 81% after the first FMT (38/47) and 91% after the second FMT treatment (43/47). Serious adverse events occurred in 2% and all-cause mortality was 2% at 90-day follow up. CONCLUSION: Our study demonstrated the safety and efficacy of FMT administered via retention enema, a simple bedside procedure, for the treatment and prevention of recurrent non-severe and severe CDI with an overall cure rate of 91%.

Production of hand-made cloned buffalo (Bubalus bubalis) embryos from non-viable somatic cells.

Use of non-viable somatic cells for hand-made cloning (HMC) can enable production of cloned animals from tissues obtained from elite or endangered dead animals. Buffalo skin fibroblast cells were rendered non-viable by heat treatment and used for HMC. Although fusion (93.6 ± 1.72 vs 67.1 ± 2.83%) and cleavage (90.3 ± 1.79 vs 65.8 ± 1.56%) rate was lower (P < 0.001) than that for controls, blastocysts could be successfully produced. However, blastocyst rate (34.1 ± 2.43 vs 6.9 ± 2.18%, P < 0.001) and total cell number of blastocysts (TCN, 221.3 ± 25.14 vs 151.1 ± 21.69, P < 0.05) were lower and apoptotic index (4.8 ± 1.06 vs 10.9 ± 1.21) was higher (P < 0.001) than that of controls. In another experiment, ear tissue of slaughterhouse buffaloes was preserved in mustard oil at room temperature for 48 h following which somatic cells were harvested by enzymatic digestion and used for HMC. Although fusion (96.8 ± 1.48 vs 84.2 ± 3.19%), cleavage (89.6 ± 3.59 vs 77.2 ± 3.99%), and blastocyst rate (36.9 ± 7.45 vs 13.1 ± 6.87%) were lower (P < 0.01), TCN (223.0 ± 27.89 vs 213.3 ± 28.21) and apoptotic index (3.97 ± 0.67 vs 5.22 ± 0.51) of blastocysts were similar to those of controls. In conclusion, HMC can be successfully used for production of blastocysts from non-viable cells and from cells obtained from freshly slaughtered buffaloes. This can pave the way for the restoration of farm or wild animals by HMC if somatic cells could be obtained within a few hours after their death.

Pseudohyperplastic variant of adenocarcinoma as a component of α-methyl-CoA-racemase (AMACR negative) carcinosarcoma of the prostate.

Carcinosarcoma (CS) or Sarcomatoid carcinoma (SC) of the prostate is a very rare malignant tumor of the prostate having an aggressive clinical course and dismal prognosis. The adenocarcinomatous element is usually of the acinar type and closely admixed with a sarcomatous component. We report a case of α-methyl-CoA-racemase (AMACR)-negative pseudohyperplastic variant of adenocarcinoma in CS. To the best of our knowledge, there have been no published case reports of this variant in CS till date. An accurate diagnosis is essential as this uncommon, aggressive cancer has limited therapeutic options.

High photosensitivity few-layered MoSe2 back-gated field-effect phototransistors.

In this paper, we report on the fabrication and optoelectronic properties of high sensitive phototransistors based on few-layered MoSe2 back-gated field-effect transistors, with a mobility of 19.7 cm² V⁻¹ s⁻¹ at room temperature. We obtained an ultrahigh photoresponsivity of 97.1 AW⁻¹ and an external quantum efficiency (EQE) of 22 666% using 532 nm laser excitation at room temperature. The photoresponsivity was improved near the threshold gate voltage; however, the selection of the silicon dioxide as a gate oxide represents a limiting factor in the ultimate performance. Thanks to their high photoresponsivity and external quantum efficiency, the few-layered MoSe2-based devices are promising for photoelectronic applications.

Targeting adipose tissue via systemic gene therapy.

Adipose tissue has a critical role in energy and metabolic homeostasis, but it is challenging to adapt techniques to modulate adipose function in vivo. Here we develop an in vivo, systemic method of gene transfer specifically targeting adipose tissue using adeno-associated virus (AAV) vectors. We constructed AAV vectors containing cytomegalovirus promoter-regulated reporter genes, intravenously injected adult mice with vectors using multiple AAV serotypes, and determined that AAV2/8 best targeted adipose tissue. Altering vectors to contain adiponectin promoter/enhancer elements and liver-specific microRNA-122 target sites restricted reporter gene expression to adipose tissue. As proof of efficacy, the leptin gene was incorporated into the adipose-targeted expression vector, package into AAV2/8 and administered intravenously to 9- to 10-week-old ob/ob mice. Phenotypic changes were measured over an 8-week period. Leptin mRNA and protein were expressed in adipose and leptin protein was secreted into plasma. Mice responded with reversal of weight gain, decreased hyperinsulinemia and improved glucose tolerance. AAV2/8-mediated systemic delivery of an adipose-targeted expression vector can replace a gene lacking in adipose tissue and correct a mouse model of human disease, demonstrating experimental application and therapeutic potential in disorders of adipose.

Gate dependent Raman spectroscopy of graphene on hexagonal boron nitride.

Raman spectroscopy, a fast and nondestructive imaging method, can be used to monitor the doping level in graphene devices. We fabricated chemical vapor deposition (CVD) grown graphene on atomically flat hexagonal boron nitride (hBN) flakes and SiO2 substrates. We compared their Raman response as a function of charge carrier density using an ion gel as a top gate. The G peak position, the 2D peak position, the 2D peak width and the ratio of the 2D peak area to the G peak area show a dependence on carrier density that differs for hBN compared to SiO2. Histograms of two-dimensional mapping are used to compare the fluctuations in the Raman peak properties between the two substrates. The hBN substrate has been found to produce fewer fluctuations at the same charge density owing to its atomically flat surface and reduced charged impurities.

Spinal 5-HT3 receptors facilitate behavioural hypersensitivity induced by elevated calcium channel alpha-2-delta-1 protein.

BACKGROUND: Peripheral nerve injury induces up-regulation of the calcium channel alpha-2-delta-1 proteins in the dorsal root ganglia and dorsal spinal cord that correlates with neuropathic pain development. Similar behavioural hypersensitivity was also observed in injury-free transgenic (TG) mice over-expressing the alpha-2-delta-1 proteins in neuronal tissues. To investigate pathways regulating alpha-2-delta-1 protein-mediated behavioural hypersensitivity, we examined whether spinal serotonergic 5-HT3 receptors are involved similarly in the modulation of behavioural hypersensitivity induced by either peripheral nerve injury in a nerve injury model or neuronal alpha-2-delta-1 over-expression in the TG model. METHODS: The effects of blocking behavioural hypersensitivity in these two models by intrathecal or systemic injections of 5-HT3 receptor antagonist, ondansetron, were compared. RESULTS: Our data indicated that the TG mice displayed similar behavioural hypersensitivities to non-painful mechanical stimulation (tactile allodynia) and painful thermal stimulation (thermal hyperalgesia) as that observed in the nerve injury model. Interestingly, tactile allodynia and thermal hyperalgesia in both models can be blocked similarly by intrathecal, but not systemic, injection of ondansetron. CONCLUSIONS: Our data suggest that spinal 5-HT3 receptors are likely to play a role in alpha-2-delta-1-mediated behavioural hypersensitivities through a descending serotonergic facilitation.

Prognostic value of cardiac troponins in elderly patients with hip fracture--a systematic review.

Cardiac troponins can be elevated in cardiac ischemic conditions or other diseases such as pulmonary embolism or renal failure, where they may predict outcome. We hypothesized that cardiac troponins offer useful prognostic information regarding morbidity and mortality in elderly hip fracture patients undergoing surgical therapy. A literature review was conducted using PubMed and CINAHL plus with full text (EBSCOhost). Articles with original data relating troponins to prognosis in elderly hip fracture patients were reviewed. Studies with patients not undergoing surgery or undergoing elective or nonhip fracture surgery were excluded. Six papers met inclusion criteria. Troponin elevation was seen in 26.7-39% of patients, while myocardial infarction, cardiac complications, and cardiac death occurred in ≤35% troponin-positive patients in four of six studies. Several noncardiac factors were associated with elevated troponin including higher American Society of Anaesthesiologists score, current smoking, reduced mobility/activity level, lower hemoglobin, and living in residential care. Patients with elevated troponin had longer lengths of stay, increased risk for discharge to long-term care facilities, and higher mortality. Increased age, male sex, and higher American Society of Anaesthesiologists score were also associated with mortality. Elevated troponin can be used as a marker of increased morbidity/mortality in elderly hip fracture patients undergoing surgery, as hypothesized, even in the absence of cardiac complications. Perioperative troponin evaluation may be useful for risk stratification, but further studies are needed to clarify risks and benefits of such testing.

The safety and efficacy of antitumour necrosis factor-alpha therapy for inflammatory bowel disease in patients post liver transplantation: a case series.

BACKGROUND: The role of antitumour necrosis factor-alpha (anti-TNF) therapy for inflammatory bowel disease (IBD) among liver transplant recipients is largely unknown given the rarity of this population and the paucity of literature on the subject. AIM: To investigate the safety and efficacy of anti-TNF therapy for refractory IBD in the post liver transplant population. METHODS: The liver transplant database at London Health Sciences Centre was searched to identify adult patients with IBD treated with anti-TNF therapy post transplantation. RESULTS: Six patients (five men, one woman) were identified, aged 28-65. All patients had cadaveric orthotopic liver transplants. Four patients required transplantation due to primary sclerosing cholangitis, one due to autoimmune hepatitis, and one due to biliary atresia. Five patients suffered from Crohn's disease and the remaining patient from indeterminate colitis. All patients were treated with infliximab 5 mg/kg every 8 weeks after undergoing induction at weeks 0, 2 and 6, with the exception of one patient. The duration of infliximab therapy ranged from 8 weeks to 4 years. Four patients treated with infliximab experienced sustained improvement of their IBD symptoms post transplantation, as documented by Harvey-Bradshaw Index scores demonstrating clinical remission. Of the remaining two patients, neither had sustained improvement of their IBD with infliximab or subsequent adalimumab. One patient was diagnosed with systemic lupus erythematosus and another with colorectal adenocarcinoma following anti-TNF therapy. Otherwise, no side effects were attributed to anti-TNF therapy. CONCLUSIONS: Based on this case series, anti-TNF therapy appears to be safe and effective for treating refractory IBD in patients post liver transplantation. These patients respond to anti-TNF therapy similar to those who have not been previously transplanted.

Bilateral hybrid oncocytoma and renal cell carcinoma.

A 26-year-old female presented with abdominal pain and distension in 2003. Clinical evaluation and imaging were suggestive of bilateral benign renal solid masses. Fine needle aspiration showed tubular cells only. Patient was kept under periodic follow up. She reported 4 years later with increase in pain and size of masses, and underwent bilateral staged nephron sparing surgery. The histopathology was reported as bilateral oncocytoma. Two years after surgery, she developed epidural spinal cord compression and liver metastasis. A decompression laminectomy and biopsy revealed conventional renal cell carcinoma (RCC). To our knowledge this is the first case report of sporadic bilateral synchronous hybrid RCC and oncocytoma in a young woman, with spinal epidural metastasis.

Neurofibromatosis 1 with pheochromocytoma.

Von Hippel-Lindau (VHL) disease includes a wide spectrum of highly vascular tumors like pheochromocytoma, cysts and adenomas of the pancreas and kidney, endolymphatic sac and renal cell carcinoma. Molecular analysis of the VHL gene is vital in these patients and their kindred. Neuroendocrine pancreatic tumors are rare and are known for their malignant and metastatic potential. We discuss an interesting case of a young lady who had a strong family history of central nervous system and spinal tumors. Our patient presented with recently detected severe hypertension. She was found to have elevated urinary normetanephrine levels; radiological imaging revealed bilateral pheochromocytomas with a pancreatic lesion. On genetic analysis, a variation, c.IVS 2 + 3 A > G, was found in the intronic region following exon 2 of the VHL gene. This variant appears novel. This patient underwent bilateral adrenalectomy (right total and left cortical sparing), distal pancreatectomy and splenectomy. Histology was diagnostic for pheochromocytoma with a neuroendocrine tumor of the pancreas. The postoperative period was uneventful. She was advised genetic screening of all her first-degree relatives.

Target localization and toxicity in dose-escalated prostate radiotherapy with image-guided approach using daily planar kilovoltage imaging.

Dose escalation with intensity-modulated radiation therapy (IMRT) for carcinoma of the prostate has augmented the need for accurate prostate localization prior to dose delivery. Daily planar kilovoltage (kV) imaging is a low-dose image-guidance technique that is prevalent among radiation oncologists. However, clinical outcomes evaluating the benefit of daily kV imaging are lacking. The purpose of this study was to report our clinical experience, including prostate motion and gastrointestinal (GI) and genitourinary (GU) toxicities, using this modality. A retrospective analysis of 100 patients treated consecutively between December 2005 and March 2008 with definitive external beam IMRT for T1c-T4 disease were included in this analysis. Prescription doses ranged from 74-78 Gy (median, 76) in 2 Gy fractions and were delivered following daily prostate localization using on-board kV imaging (OBI) to localize gold seed fiducial markers within the prostate. Acute and late toxicities were graded as per the NCI CTCAEv3.0. The median follow-up was 22 months. The magnitude and direction of prostate displacement and daily shifts in three axes are reported. Of note, 9.1% and 12.9% of prostate displacements were ≥ 5 mm in the anterior-posterior and superior-inferior directions, respectively. Acute grade 2 GI and GU events occurred in 11% and 39% of patients, respectively, however no grade 3 or higher acute GI or GU events were observed. Regarding late toxicity, 2% and 17% of patients developed grade 2 toxicities, and similarly no grade 3 or higher events had occurred by last follow-up. Thus, kV imaging detected a substantial amount of inter-fractional displacement and may help reduce toxicity profiles, especially high grade events, by improving the accuracy of dose delivery.