Sex hormone levels in drug-naïve, first-episode patients with psychosis.

Aim: Sex differences have long been reported in schizophrenia leading to the hypothesis that sex hormones may be implicated in the pathophysiology of the disorder. We assessed gonadal hormones during the fasted state in drug-naïve patients with psychosis.Method: Fasting serum concentrations of follicular-stimulating hormone (FSH) and luteinizing hormone (LH), testosterone, free-testosterone, Sex Hormone Binding Globulin (SHBG) and oestradiol (E2) were compared between a group of 55 newly diagnosed, drug-naïve, first-episode men with psychosis and a group of 55 healthy controls, matched for age, smoking status and BMI. Testosterone, free-testosterone and SHBG were compared between a group of 32 drug-naïve, first-episode females with psychosis and a group of 32 healthy controls matched for age, smoking status and BMI.Results: Testosterone and free-testosterone levels were significantly lower in the patients' group and SHBG levels significantly higher in the patients' group compared to those in healthy controls. The two female groups had similar values in the hormones which were measured.Conclusion: Our findings provide evidence of lower testosterone and free-testosterone levels and increased SHBG levels in drug-naïve, first-episode males with psychosis.KEY POINTSReduced testosterone and free-testosterone levels in drug-naive, first-episode males with psychosis.Increased SHBG levels in drug-naive first-episode males with psychosis.No difference in FSH, LH and E2 levels between drug-naive first episode males with psychosis and controls.No difference in testosterone, free-testosterone and SHBG levels between drug-naive, first-episode women with psychosis and controls.

Kilohertz binary phase modulator for pulsed laser sources using a digital micromirror device.

The controlled modulation of an optical wavefront is required for aberration correction, digital phase conjugation, or patterned photostimulation. For most of these applications, it is desirable to control the wavefront modulation at the highest rates possible. The digital micromirror device (DMD) presents a cost-effective solution to achieve high-speed modulation and often exceeds the speed of the more conventional liquid crystal spatial light modulator but is inherently an amplitude modulator. Furthermore, spatial dispersion caused by DMD diffraction complicates its use with pulsed laser sources, such as those used in nonlinear microscopy. Here we introduce a DMD-based optical design that overcomes these limitations and achieves dispersion-free high-speed binary phase modulation. We show that this phase modulation can be used to switch through binary phase patterns at the rate of 20 kHz in two-photon excitation fluorescence applications.

Treatment with the first TNF inhibitor in rheumatoid arthritis patients in the Hellenic Registry of Biologic Therapies improves quality of life especially in young patients with better baseline functional status.

OBJECTIVES: To assess in daily practice in patients with rheumatoid arthritis (RA) the effect of treatment with first tumour necrosis factor-α inhibitor (TNFi) in quality of life (Qol), disease activity and depict possible baseline predictors for gains in Qol. METHODS: Patients followed prospectively by the Hellenic Registry of Biologic Therapies were analysed. Demographics were recorded at baseline, while RA-related characteristics at baseline and every 6 months. Paired t-tests were used to detect divergences between patient-reported (Health Assessment Questionnaire (HAQ), EuroQol (EQ-5D)) and clinical tools (Disease Activity Score-28 joints (DAS28)). Clinical versus self-reported outcomes were examined via cross-tabulation analysis. Multiple regression analysis was performed for identifying baseline predictors of improvements in QALYs. RESULTS: We analysed 255 patients (age (mean±SD) 57.1±13.0, disease duration 9.2±9.1 years, prior non-biologic disease-modifying anti-rheumatic drugs 2.3±1.2). Baseline EQ-5D, HAQ and DAS28 were 0.36 (0.28), 1.01 (0.72) and 5.9 (1.3), respectively, and were all significantly improved after 12 months (0.77 (0.35), 0.50 (0.66), 3.9 (1.5), respectively, p<0.05 for all). 90% of patients who improved from high to a lower DAS28 status (low-remission or moderate) had clinically important improvement in Qol (phi-coefficient=0.531,p<0.05). Independent predictors of gains in Qol were lower baseline HAQ, VAS global and younger age (adjusted R2=0.27). CONCLUSIONS: In daily practice TNFi improve both disease activity and Qol for the first 12 months of therapy. 90% of patients who improved from high to a lower DAS28 status had clinically important improvement in Qol. Younger patients starting with lower HAQ and VAS global are more likely to benefit.

Aerobic, resistance and combined training and detraining on body composition, muscle strength, lipid profile and inflammation in coronary artery disease patients.

Fifty-six elderly individuals diagnosed with coronary artery disease participated in the study and were divided into four groups: an aerobic exercise group, a resistance exercise group, a combined (aerobic + resistance) exercise group and a control group. The three exercise groups participated in 8 months of exercise training. Before, at 4 and at 8 months of the training period as well as at 1, 2 and 3 months after training cessation, muscle strength was measured and blood samples were collected. The resistance exercise caused significant increases mainly in muscle strength whereas aerobic exercise caused favourable effects mostly on lipid and apolipoprotein profiles. On the other hand, combined exercise caused significant favourable effects on both physiological (i.e. muscle strength) and biochemical (i.e. lipid and apolipoprotein profile and inflammation status) parameters, while the return to baseline values during the detraining period was slower compared to the other exercise modalities.

Digital confocal microscopy through a multimode fiber.

Acquiring high-contrast optical images deep inside biological tissues is still a challenging problem. Confocal microscopy is an important tool for biomedical imaging since it improves image quality by rejecting background signals. However, it suffers from low sensitivity in deep tissues due to light scattering. Recently, multimode fibers have provided a new paradigm for minimally invasive endoscopic imaging by controlling light propagation through them. Here we introduce a combined imaging technique where confocal images are acquired through a multimode fiber. We achieve this by digitally engineering the excitation wavefront and then applying a virtual digital pinhole on the collected signal. In this way, we are able to acquire images through the fiber with significantly increased contrast. With a fiber of numerical aperture 0.22, we achieve a lateral resolution of 1.5µm, and an axial resolution of 12.7µm. The point-scanning rate is currently limited by our spatial light modulator (20Hz).

Delivery of focused short pulses through a multimode fiber.

Light propagation through multimode fibers suffers from spatial distortions that lead to a scrambled intensity profile. In previous work, the correction of such distortions using various wavefront control methods has been demonstrated in the continuous wave case. However, in the ultra-fast pulse regime, modal dispersion temporally broadens a pulse after propagation. Here, we present a method that compensates for spatial distortions and mitigates temporal broadening due to modal dispersion by a selective phase conjugation process in which only modes of similar group velocities are excited. The selectively excited modes are forced to follow certain paths through the multimode fiber and interfere constructively at the distal tip to form a focused spot with minimal temporal broadening. We demonstrate the delivery of focused 500 fs pulses through a 30 cm long step-index multimode fiber. The achieved pulse duration corresponds to approximately 1/30th of the duration obtained if modal dispersion was not controlled. Moreover, we measured a detailed two-dimensional map of the pulse duration at the output of the fiber and confirmed that the focused spot produces a two-photon absorption effect. This work opens new possibilities for ultra-thin multiphoton imaging through multimode fibers.

Isotropic inverse-problem approach for two-dimensional phase unwrapping.

We propose a new technique for two-dimensional phase unwrapping. The unwrapped phase is found as the solution of an inverse problem that consists in the minimization of an energy functional. The latter includes a weighted data fidelity term that favors sparsity in the error between the true and wrapped phase differences, as well as a regularizer based on higher-order total variation. One desirable feature of our method is its rotation invariance, which allows it to unwrap a much larger class of images compared to the state of the art. We demonstrate the effectiveness of our method through several experiments on simulated and real data obtained through the tomographic phase microscope. The proposed method can enhance the applicability and outreach of techniques that rely on quantitative phase evaluation.

Transferring the emergence profile from the provisional to the final restoration.

UNLABELLED: In implant restorations, the ability to manage the response of soft tissue properly and achieve a proper emergence profile is a primary goal for the clinician. The desirable emergence profile can be formed by the use of the provisional restorations. Once this task is achieved, the soft tissue contour must be transferred accurately to the final restoration. In this technique article, four different methods are presented for transferring the emergence profile: the modification of the impression post by adding composite resin intraorally or extraorally, the fabrication of a working cast mimicking the soft tissue contour, and the use of CAD/CAM technology. Each technique presents certain advantages and disadvantages. The choice, therefore, relies on the clinician's judgment depending on the available materials, time, and familiarization with the necessary steps. The aim of this technique article is to describe, evaluate, and compare with the use of clinical examples these four techniques presented for the transfer of the emergence profile from the provisional to the final restoration. CLINICAL SIGNIFICANCE: The application of these simple, yet important, techniques can not only help achieve optimal esthetics but also contribute to the maintenance of peri-implant health. Especially in esthetically demanding cases-such as in implant restorations in the anterior area or in cases with high lip line-their application can lead to a more predictable final result.

Eosin, blue LEDs and DIPEA are employed in a simple synthesis of (poly)cyclic O,O- and N,O-acetals.

A simple procedure for the synthesis of (poly)cyclic O,O- and N,O-acetals from various enol ethers, N-acyl enamines or Boc-protected enamines has been developed. The key step is a photocatalytic Stork-Ueno-type cylization using the very simple metal-free conditions of catalytic eosin, diisopropylamine in the green solvent ethanol with blue LED irradition.

Advancing Parkinson's Disease Diagnostics: The Potential of Arylpyrazolethiazole Derivatives for Imaging α-Synuclein Aggregates.

The development of positron emission tomography (PET) tracers capable of detecting α-synuclein (α-syn) aggregates in vivo would represent a breakthrough for advancing the understanding and enabling the early diagnosis of Parkinson's disease and related disorders. It also holds the potential to assess the efficacy of therapeutic interventions. However, this remains challenging due to different structures of α-syn aggregates, the need for selectivity over other structurally similar amyloid proteins, like amyloid-ß (Aß), which frequently coexist with α-syn pathology, and the low abundance of the target in the brain that requires the development of a high-affinity ligand. To develop a successful PET tracer for the central nervous system (CNS), stringent criteria in terms of polarity and molecular size must also be considered, as the tracer must penetrate the blood-brain barrier and have low nonspecific binding to brain tissue. Here, we report a series of arylpyrazolethiazole (APT) derivatives, rationally designed from a structure-activity relationship study centered on existing ligands for α-syn fibrils, with a particular focus on the selectivity toward α-syn fibrils and control of physicochemical properties suitable for a CNS PET tracer. In vitro competition binding assays performed against [3H]MODAG-001 using recombinant α-syn and Aß1-42 fibrils revealed APT-13 with an inhibition constant of 27.8 ± 9.7 nM and a selectivity of more than 3.3 fold over Aß. Radiolabeled [11C]APT-13 demonstrated excellent brain penetration in healthy mice with a peak standardized uptake value of 1.94 ± 0.29 and fast washout from the brain (t 1/2 = 9 ± 1 min). This study highlights the potential of APT-13 as a lead compound for developing PET tracers to detect α-syn aggregates in vivo.

Dynamic bending compensation while focusing through a multimode fiber.

Multimode fiber endoscopes have recently been shown to provide sub-micrometer resolution, however, imaging through a multimode fiber is highly sensitive to bending. Here we describe the implementation of a coherent beacon source placed at the distal tip of the multimode fiber, which can be used to compensate for the effects of bending. In the first part of this paper, we show that a diffraction limited focused spot can be generated at the distal tip of the multimode fiber using the beacon. In the second part, we demonstrate focusing even when the fiber is bent by dynamically compensating for it. The speckle pattern at the proximal fiber end, generated by the beacon source placed at its distal end, is highly dependent on the fiber conformation. We experimentally show that by intensity correlation, it is possible to identify the fiber conformation and maintain a focus spot while the fiber is bent over a certain range. Once the fiber configuration is determined, previously calibrated phase patterns could be stored for each fiber conformation and used to scan the distal spot and perform imaging.

Hydrogen sulfide induces systemic tolerance to salinity and non-ionic osmotic stress in strawberry plants through modification of reactive species biosynthesis and transcriptional regulation of multiple defence pathways.

Hydrogen sulfide (H2S) has been recently found to act as a potent priming agent. This study explored the hypothesis that hydroponic pretreatment of strawberry (Fragaria × ananassa cv. Camarosa) roots with a H2S donor, sodium hydrosulfide (NaHS; 100 µM for 48 h), could induce long-lasting priming effects and tolerance to subsequent exposure to 100mM NaCI or 10% (w/v) PEG-6000 for 7 d. Hydrogen sulfide pretreatment of roots resulted in increased leaf chlorophyll fluorescence, stomatal conductance and leaf relative water content as well as lower lipid peroxidation levels in comparison with plants directly subjected to salt and non-ionic osmotic stress, thus suggesting a systemic mitigating effect of H2S pretreatment to cellular damage derived from abiotic stress factors. In addition, root pretreatment with NaHS resulted in the minimization of oxidative and nitrosative stress in strawberry plants, manifested via lower levels of synthesis of NO and H(2)O(2) in leaves and the maintenance of high ascorbate and glutathione redox states, following subsequent salt and non-ionic osmotic stresses. Quantitative real-time RT-PCR gene expression analysis of key antioxidant (cAPX, CAT, MnSOD, GR), ascorbate and glutathione biosynthesis (GCS, GDH, GS), transcription factor (DREB), and salt overly sensitive (SOS) pathway (SOS2-like, SOS3-like, SOS4) genes suggests that H2S plays a pivotal role in the coordinated regulation of multiple transcriptional pathways. The ameliorative effects of H2S were more pronounced in strawberry plants subjected to both stress conditions immediately after NaHS root pretreatment, rather than in plants subjected to stress conditions 3 d after root pretreatment. Overall, H2S-pretreated plants managed to overcome the deleterious effects of salt and non-ionic osmotic stress by controlling oxidative and nitrosative cellular damage through increased performance of antioxidant mechanisms and the coordinated regulation of the SOS pathway, thus proposing a novel role for H2S in plant priming, and in particular in a fruit crop such as strawberry.

Increasing the imaging capabilities of multimode fibers by exploiting the properties of highly scattering media.

We present a design that exploits the focusing properties of scattering media to increase the resolution and the working distance of multimode fiber (MMF)-based imaging devices. Placing a highly scattering medium in front of the distal tip of the MMF enables the formation of smaller sized foci at increased working distances away from the fiber tip. We perform a parametric study of the effect of the working distance and the separation between the fiber and the scattering medium on the focus size. We experimentally demonstrate submicrometer focused spots as far away as 800 µm with 532 nm light.

Focusing and scanning light through a multimode optical fiber using digital phase conjugation.

We demonstrate for the first time to our knowledge a digital phase conjugation technique for generating a sharp focus point at the end of a multimode optical fiber. A sharp focus with a contrast of 1800 is experimentally obtained at the tip of a 105 µm core multimode fiber. Scanning of the focal point is also demonstrated by digital means. Effects from illumination and fiber bending are addressed.

Diospyrobezoar Formation in Patient With Sleeve Gastrectomy.

The ingestion of Asian persimmons, Diospyros kaki, is a known cause of gastric bezoars. Patients with a history of gastric operations are at high risk for formation. Different forms of bariatric surgery have been implicated, but literature for bezoar following a sleeve gastrectomy is scarce. This case report describes the pathogenesis, clinical course, and definitive management of gastric diospyrobezoar following a sleeve gastrectomy. With the rising incidence of bariatric procedures being performed, providers should include bezoar in the differential diagnosis in patients with suspected gastric outlet obstruction and should be aware of treatment options for this patient population.

Assessing the effectiveness of public health interventions for Covid-19 in Greece and Cyprus.

In this article, we statistically examine the effectiveness of non-pharmaceutical interventions (NPIs) implemented by the national governments of Greece and Cyprus during 2020 to (a) limit the spread of the SARS-CoV-2 virus, and (b) mitigate the economic fallout brought about by the Covid-19 pandemic. Applying a modified health belief model, we hypothesize that behavioral outcomes at the policy level are a function of NPIs, perceived severity, and social context. We employ a Prais-Winsten estimation in 2-week averages and report panel-corrected standard errors to find that NPIs have clear, yet differential, effects on public health and the economy in terms of statistical significance and time lags. The study provides a critical framework to inform future interventions during emerging pandemics.

En este artículo, examinamos estadísticamente la efectividad de las intervenciones no farmacéuticas (NPI) implementadas por los gobiernos nacionales de Grecia y Chipre durante 2020 para (a) limitar la propagación del virus SARS­CoV­2 y (b) mitigar las consecuencias económicas provocadas por la pandemia de Covid­19. Al aplicar un modelo de creencias de salud modificado, planteamos la hipótesis de que los resultados de comportamiento a nivel de política son una función de las NPI, la gravedad percibida y el contexto social. Empleamos una estimación de Prais­Winsten en promedios de dos semanas e informamos los errores estándar corregidos del panel para encontrar que las NPI tienen efectos claros, aunque diferenciales, en la salud pública y la economía en términos de importancia estadística y retrasos. El estudio proporciona un marco crítico para informar futuras intervenciones durante las pandemias emergentes.

Restoration of localised erosive wear using a combination of dental materials: a conservative approach.

Objectives To present the treatment approach for the restoration of localised anterior erosive wear using a combination of dental materials.Clinical considerations A patient presented in a private dental practice concerned about the aesthetics of his anterior teeth. The patient's history and clinical examination revealed erosive wear on the labial and palatal aspects of his maxillary central incisors and right lateral incisor. The formulated treatment plan was to restore the teeth in a conservative way. A diagnostic wax-up was performed and confirmed with the patient with chairside mock-up. The treatment provided included direct composite restorations, replacement of a porcelain-fused-to-metal crown on his left lateral incisor with a porcelain-fused-to-zirconia crown, and lithium disilicate ceramic veneers on the worn labial surfaces of the central incisors and the right lateral incisor. The preparations for the ceramic veneers were carried out with the aid of the diagnostic mock-up, thus minimising the need for tooth removal of the worn teeth.Conclusions Pre-operative planning for tooth surface loss cases can help to ensure that little or no remaining tooth structure is removed during the restorative procedures. A strict bonding protocol is crucial to ensure longevity of the restorations.

Rare Presentation of a Metastatic Pancreatic Neuroendocrine Neoplasm Presenting with Atrial Flutter.

Pancreatic neuroendocrine neoplasms (PanNENs) rarely secrete serotonin, which is the main cause of carcinoid syndrome. One of its unusual manifestations is carcinoid heart disease or Hedinger's syndrome which is seldom accompanied by cardiac arrhythmias. We report the case of an 88-year-old woman who presented with recently experienced episodes of palpitations and a newly developed atrial flutter with a ventricular rate of 130 beats per minute. Echocardiography revealed thickened and tethered tricuspid and pulmonary valve leaflets causing severe valvular regurgitation and right ventricular dilatation. Episodes of intermittent diarrhoea over the previous 2 years were mentioned, making carcinoid syndrome our working diagnosis. The 5-hydroxyindoleacetic acid (5-HIAA) levels in a 24-hour urine collection specimen were elevated. Conventional imaging studies and a Ga-68 dodecane tetraacetic acid tyrosine-3-octreotate (DOTATATE) positron emission tomography/computer tomography (PET/CT) scan revealed the presence of a metastatic PanNEN arising from the pancreatic tail. The patient was managed with lanreotide and telotristat with remarkable improvement of her symptoms. To our knowledge, this is the first reported case of carcinoid syndrome presenting with atrial flutter as the initial symptom. LEARNING POINTS: Ultrasonography findings can indicate or lead to the diagnosis of carcinoid heart disease or Hedinger's syndrome.Clinicians should investigate rarer causes of atrial flutter when common ones are excluded.Even in advanced metastatic disease, complete remission of symptoms may be achieved with somatostatin analogues along with telotristat ethyl.