Vitamin D and Ulcerative Colitis: Is There a Relationship with Disease Extent?

INTRODUCTION: Patients with ulcerative colitis (UC) can suffer from low serum vitamin D that can result in complications such as low bone mineral density. It can also reflect underlying disease severity. METHODS: One hundred and ninety-seven patients previously diagnosed with UC from 2 European centers were prospectively recruited through the out-patient clinics. Clinical features (Montreal Classification, age, gender, previous and current medications, surgery), disease activity (Simple Clinical Colitis Activity Index [SCCAI]), blood investigations including serum inflammatory markers, and serum vitamin D were analyzed. The vitamin D levels were compared to a group of age- and gender-matched healthy controls. RESULTS: Mean vitamin D levels were lower in patients with UC (54.6 nmol/L) than in controls (80.7 nmol/L; p = 0.0001). Mean vitamin D levels was lowest in patients with extensive UC (E3; p = 0.0001). Serum vitamin D was not significantly different across treatment groups (p = 0.876). There was no statistical difference in vitamin D levels across patients receiving calcium and vitamin D supplements (p = 0.35) and there was no statistical correlation with SCCAI (p = 0.22). CONCLUSIONS: This study confirms the existence of low serum vitamin D in patients with UC when compared to healthy controls. It also provides evidence of an existing relationship between disease extent and serum vitamin D.

A pyridinium/anilinium [2]catenane that operates as an acid-base driven optical switch.

A two-station [2]catenane containing a large macrocycle with two different recognition sites, one bis(pyridinium)ethane and one benzylanilinium, as well as a smaller DB24C8 ring was synthesized and characterized. 1H NMR spectroscopy showed that the DB24C8 ring can shuttle between the two recognition sites depending on the protonation state of the larger macrocycle. When the aniline group is neutral, the DB24C8 ring resides solely at the bis(pyridinium)ethane site, while addition of acid forms a charged benzylanilinium site. The DB24C8 then shuttles between the two charged recognition sites with occupancy favoring the bis(pyridinium)ethane site by a ratio of 4:1. The unprotonated [2]catenane has a deep yellow/orange color when the DB24C8 ring resides solely at the bis(pyridinium)ethane site and changes to colorless when the crown ether is shuttling (i.e., circumrotating) back and forth between the two recognition sites thus optically signalling the onset of the shuttling dynamics.

Measuring markers of liver function using a micropatterned paper device designed for blood from a fingerstick.

This paper describes a paper-based microfluidic device that measures two enzymatic markers of liver function (alkaline phosphatase, ALP, and aspartate aminotransferase, AST) and total serum protein. A device consists of four components: (i) a top plastic sheet, (ii) a filter membrane, (iii) a patterned paper chip containing the reagents necessary for analysis, and (iv) a bottom plastic sheet. The device performs both the sample preparation (separating blood plasma from erythrocytes) and the assays; it also enables both qualitative and quantitative analysis of data. The data obtained from the paper-microfluidic devices show standard deviations in calibration runs and "spiked" standards that are acceptable for routine clinical use. This device illustrates a type of test useable for a range of assays in resource-poor settings.

Oesophagomediastinal fistula: a rare complication of tuberculosis.

We report a case of a woman from Thailand, living in Malta, who was diagnosed with concomitant tuberculosis (TB) and HIV with depleted CD4 count. Her case was further complicated by the formation of a fistula between the mediastinal lymph nodes and the oesophagus, an unusual finding but for which she had many risk factors. The diagnosis was suspected on CT scan of the thorax and confirmed via upper gastrointestinal endoscopy. Following the commencement of both anti-TB and antiretroviral therapy, she suffered a lapse of immune reconstitution inflammatory syndrome but with aggressive medical management eventually made a full recovery without the need for surgical intervention.

Correction: The first wave of COVID-19 in Malta; a national cross-sectional study.

[This corrects the article DOI: 10.1371/journal.pone.0239389.].

Leishmania donovani mucosal leishmaniasis in Malta.

We report a case of a 76-year-old British man living in Malta who presented with a 7-month history of recurrent epistaxis and an enlarging right nasal vestibular lesion. Of note, his medical history included rheumatoid arthritis for which he was on long-term methotrexate. Blood results were unremarkable other than a mild lymphopaenia. Despite the use of various antibiotics and intranasal steroids, the lesion failed to resolve. This was eventually biopsied, and the histological picture was that of mucosal leishmaniasis. Leishmania donovani complex was detected by PCR. The patient was treated with liposomal amphotericin B on alternate days for a total of 20 doses. The lesion was found to have healed well at follow-up and the patient denied any further episodes of epistaxis.

The first wave of COVID-19 in Malta; a national cross-sectional study.

INTRODUCTION: The COVID-19 pandemic has posed major challenges to all aspects of healthcare. Malta's population density, large proportion of elderly and high prevalence of diabetes and obesity put the country at risk of uncontrolled viral transmission and high mortality. Despite this, Malta achieved low mortality rates compared to figures overseas. The aim of this paper is to identify key factors that contributed to these favorable outcomes. METHODS: This is a retrospective, observational, nationwide study which evaluates outcomes of patients during the first wave of the pandemic in Malta, from the 7th of March to the 24th of April 2020. Data was collected on demographics and mode of transmission. Hospitalization rates to Malta's main general hospital, Mater Dei Hospital, length of in-hospital stay, intensive care unit admissions and 30-day mortality were also analyzed. RESULTS: There were 447 confirmed cases in total; 19.5% imported, 74.2% related to community transmission and 6.3% nosocomially transmitted. Ninety-three patients (20.8%) were hospitalized, of which 4 were children. Patients with moderate-severe disease received hydroxychloroquine and azithromycin, in line with evidence available at the time. A total of 4 deaths were recorded, resulting in an all-cause mortality of 0.89%. Importantly, all admitted patients with moderate-severe disease survived to 30-day follow up. CONCLUSION: Effective public health interventions, widespread testing, remote surveillance of patients in the community and a low threshold for admission are likely to have contributed to these favorable outcomes. Hospital infection control measures were key in preventing significant nosocomial spread. These concepts can potentially be applied to stem future outbreaks of viral diseases. Patients with moderate-severe disease had excellent outcomes with no deaths reported at 30-day follow up.

Controlling the kinetics of contact electrification with patterned surfaces.

This communication describes a new approach for controlling static charging (contact electrification), and resulting electrical discharging, that occurs when two contacting materials separate. The prevention of contact electrification is an important problem; unwanted adhesion between oppositely charged materials, spark-initiated explosions, and damage to microelectronic circuitry are some of the deleterious effects of static charging. Current strategies for controlling contact electrification rely upon dissipating an accumulated charge by making contacting surfaces conductive and, therefore, can be difficult to implement with electrically insulating materials. Specifically, using our understanding of the ion-transfer mechanism of contact electrification, we patterned glass slides with negatively charging areas (clean glass) and positively charging areas (glass silanized with a cationic siloxane terminated with a quaternary ammonium group). The rate of charge separation due to a steel sphere rolling on the patterned glass surface correlated linearly with the percentage of the glass surface that was silanized; the rate of charge transfer was minimal when 50% of the glass surface area was silanized. Patterned surfaces also prevented electrical discharges between electrically conducting (bare steel) or insulating (acrylate-coated steel) spheres rolling on the glass, because the rate of charging was sufficiently slow to prevent electric fields greater than the dielectric strength of air to develop. This strategy for preventing static charging therefore does not require one of the two contacting surfaces to be electrically conductive. More generally, these results show that our enhanced understanding of the ion-transfer mechanism of contact electrification enables the rational design of chemically tailored surfaces for functional electrets.

Paper microzone plates.

This paper describes 96- and 384-microzone plates fabricated in paper as alternatives to conventional multiwell plates fabricated in molded polymers. Paper-based plates are functionally related to plastic well plates, but they offer new capabilities. For example, paper-microzone plates are thin (approximately 180 microm), require small volumes of sample (5 microL per zone), and can be manufactured from inexpensive materials ($0.05 per plate). The paper-based plates are fabricated by patterning sheets of paper, using photolithography, into hydrophilic zones surrounded by hydrophobic polymeric barriers. This photolithography used an inexpensive formulation photoresist that allows rapid (approximately 15 min) prototyping of paper-based plates. These plates are compatible with conventional microplate readers for quantitative absorbance and fluorescence measurements. The limit of detection per zone loaded for fluorescence was 125 fmol for fluorescein isothiocyanate-labeled bovine serum albumin, and this level corresponds to 0.02 the quantity of analyte per well used to achieve comparable signal-to-noise in a 96-well plastic plate (using a solution of 25 nM labeled protein). The limits of detection for absorbance on paper was approximately 50 pmol per zone for both Coomassie Brilliant Blue and Amaranth dyes; these values were 0.4 that required for the plastic plate. Demonstration of quantitative colorimetric correlations using a scanner or camera to image the zones and to measure the intensity of color, makes it possible to conduct assays without a microplate reader.

Fever of unknown origin: a challenging case.

We report a case of Cogan's syndrome presenting as fever of unknown origin in a 31-year-old woman who was admitted to the hospital with a 7-week history of fever, night sweats and other constitutional symptoms. The diagnosis remained elusive despite numerous investigations, and the patient subsequently developed rash, episcleritis, dizziness and sensorineural hearing loss. While initially thought to be a postinflammatory response to a previous infection, confirmation of the rash as a vasculitis together with the audiovestibular and ocular involvement led to a clinical diagnosis of Cogan's syndrome. This was further corroborated by resolution of her symptoms once immunosuppressive therapy was instituted. Early recognition of Cogan's syndrome is crucial to reducing the risk of serious complications through the timely initiation of treatment.

Optically sensed, molecular shuttles driven by acid-base chemistry.

A pair of bistable [2]rotaxane, molecular shuttles were prepared that combine 1,2-bis(pyridinium)ethane and benzylanilinium recognition sites; acid-base controlled shuttling of DB24C8 was accompanied by a change in colour and/or fluorescence intensity.

Push-pull [2]pseudorotaxanes. Electronic control of threading by switching ON/OFF an intramolecular charge transfer.

[reaction: see text] Addition of acid and base allows switching between two different structures in a push-pull bis(pyridinium)ethane axle, controlling its ability to form [2]pseudorotaxanes with a dibenzo-24-crown-8 ether wheel.

A mechanical "flip-switch". Interconversion between co-conformations of a [2]rotaxane with a single recognition site.

[2]Rotaxanes utilising the 1,2-bis(pyridinium)ethane, 24-crown-8 motif can exist in two distinct co-conformations whose relative abundances are solvent dependent.

[2]pseudorotaxane formation with N-benzylanilinium axles and 24-crown-8 ether wheels.

[reaction: see text] As a hybrid of the N,N-dibenzylammonium and 1,2-bis(pyridinium)ethane axles, various N-benzylanilinium cations were investigated as suitable axles for the formation of [2]pseudorotaxanes with the 24-membered crown ethers 24C8 and DB24C8. The effect of electron-donating OCH(3) and electron-withdrawing CF(3) groups on both the anilinium and benzyl aromatic rings was studied. Formation constants and structural details were compared to the [2]pseudorotaxanes formed by the two aforementioned dibenzylammonium and 1,2-bis(pyridinium)ethane axles.

Colour coding the co-conformations of a [2]rotaxane flip-switch.

Fine-tuning the charge transfer chromophores in a series of [2]rotaxane flip-switches yields a unique optical signal (purple colour) for one of the interactions allowing for facile determination of the position of the flip-switch equilibrium.

A versatile template for the formation of [2]pseudorotaxanes. 1,2-Bis(pyridinium)ethane axles and 24-crown-8 ether wheels.

Linear 1,2-bis(pyridinium)ethane 'axles' and macrocyclic 24-membered crown ether 'wheels' (, and ) combine to form [2]pseudorotaxanes. These interpenetrated adducts are held together by N+...O ion-dipole interactions, a series of C-H...O hydrogen bonds and pi-stacking between electron-poor pyridinium rings of the axle and electron-rich catechol rings of the wheel. 1H NMR spectroscopy was used to identify the structural details of the interaction and to determine the thermodynamics of the binding process in solution. Analysis of nine of these adducts by single crystal X-ray crystallography allowed a detailed study of the non-covalent interactions in the solid state. A wide variety of structural changes could be made to the system. The versatility and potential of the template for the construction of permanently interlocked structures such as rotaxanes and catenanes is discussed.