Should Histoplasmosis be Screened for Before Initiation of Tumour Necrosis Factor Alpha Inhibitors?

Histoplasmosis is a soil-based dimorphic fungus endemic to the Midwest and Southeastern United States and is responsible for infection through inhalation of conidia. Infection is usually asymptomatic, as the fungal growth is contained by formation of granulomas. However, dissemination can occur in immunocompromised hosts due to the lack of optimal activity of interferon gamma, tumour necrosis factor alpha (TNF-alpha) and interleukin-17. There is a significant overlap between the symptomatology of histoplasmosis and granulomatosis with polyangiitis (GPA). We report a case of a 48-year-old female who presented with high-grade fever, worsening generalised weakness and tachycardia. She had a previous history of bilateral cavitary lung lesions for which she was evaluated at an outside facility. As her entire infectious investigation was negative and found to be positive for antineutrophil cytoplasmic antibody (ANCA), a diagnosis of GPA was made, and she was initiated on rituximab infusions 7 weeks prior to her presentation to our facility. Repeat infectious investigations at our facility were positive for (1-3)-ß-D-glucan test and urine histoplasma antigen. Prompt discontinuation of rituximab and initiation of systemic antifungal therapy led to clinical improvement. Based on this experience, we highlight the association of histoplasma with ANCA positivity along with the importance of closely monitoring these patients for possible clinical worsening after the initiation of TNF-alpha inhibitors, despite the negative infectious work-up. Also routine screening or pre-emptive therapy for histoplasmosis before the initiation of TNF-inhibitors is not recommended. LEARNING POINTS: Histoplasmosis is associated with ANCA positivity.Despite the negative investigations for histoplasmosis and criteria for GPA being met, patients should be closely monitored for possible clinical worsening after the initiation of immunosuppressive therapy, especially TNF-alpha inhibitors.Current guidelines are not recommending routine screening or pre-emptive therapy for histoplasmosis before initiation of TNF-alpha inhibitors.

White Light Emission via Dual Thermally Activated Delayed Fluorescence from a Single-Component Phenothiazines-Diphenyl Quinoline Conjugate.

White light emission (WLE) via dual thermally activated delayed fluorescence (TADF) from a single-component-based organic system remains challenging as a result of the difficulty in design. Here, we introduce a conformational isomerization approach to achieve WLE from a twisted donor-acceptor (PTzQP1) that comprises two phenothiazines covalently attached to the 6,8-isomeric positions of 2,4-diphenyl quinoline via two C-N single bonds. Spectroscopic studies and quantum chemistry calculations revealed that PTzQP1 shows WLE via simultaneous blue TADF and orange TADF covering the visible range (420-800 nm) with a photoluminescence quantum yield of 45 ± 2% and Commission Internationale de l'Éclairage (CIE) coordinates of 0.30, 0.33. The dual TADF features with high rates of reverse intersystem crossing (kRISC1 = 1.38 × 107 ± 0.24 s-1 and kRISC2 = 5.04 × 106 ± 0.32 s-1) are realized as a result of the low singlet-triplet gaps (S1EQ-T1EQ = 0.04 eV and S1QA-T1QA = 0.05 eV) of the quasi-axial (QA) and quasi-equatorial (QE) conformers. This finding is expected to provide a new direction for designing high-energy-efficient WLE emitters.

Carbazole-Benzonitrile-Norbornadiene Conjugates for Photothermally Reversible Ambient Phosphorescence.

Organic photoswitches have attracted significant attention across various fields, such as sensing, bioimaging, photopharmacology, molecular machines, and solar energy storage. However, as a result of design complexities, achieving photothermally reversible ambient phosphorescence switching in the condensed state remains elusive. Herein, we explore the impact of norbornadiene (NBD)/quadricyclane (QC) substitution at position 5 of the benzonitrile acceptor covalently attached to the carbazole donor on photothermally reversible luminescence switching. Experimental investigations demonstrated that the CzN and TBCzN switches exhibited photothermally reversible fluorescence switching in solution. Moreover, in the condensed state, fluorescence and ambient phosphorescence switching were observed as a result of a low singlet-triplet (ΔEST) gap (CzN ⇆ CzQ, ΔESTCzN/CzQ = 0.05/0.28 eV; TBCzN ⇆ TBCzQ, ΔESTTBCzN/TBCzQ = 0.06/0.09 eV). Reversible ambient phosphorescence switching is primarily influenced by modulation of acceptor conjugation resulting from NBD ⇆ QC switching. This approach may provide important clues for the design of visible-light-absorbing photothermally reversible phosphorescent materials.

Conformational Effect of Catechol-Terephthalonitrile Emitters Leading to Ambient Violet Phosphorescence.

Organic ambient violet phosphorescent (AVP) materials are of great interest due to their involvement of high energy and longer-lived triplet excitons. Here, we show three fused ring functionalized donor-acceptor-donor (D-A-D/D-A-D') emitters (BPT1-BPT3), in which two catechol-based donors (3,4-dihydroxybenzophenone, catechol, or 3,5-ditert-butylcatechol) are covalently fused to the terephthalonitrile acceptor via four O-C single bonds. Spectroscopic analysis revealed that all the molecules show AVP (∼390-394 nm, τAVP = 73-101 µs) with phosphorescence quantum yields (ϕP) of 1.8-27.4% due to low singlet-triplet gaps (0.036-0.046 eV) and conformational effects. BPT3 with bulky tert-butyl groups increases AVP (ϕP = 27.4%). Quantum chemistry calculations reveal flat (F1) and twisted (F2) conformers (ground state) with a low energy difference (∼4-5 kcal/mol) for all molecules; the F1 conformer is responsible for efficient AVP, while weak blue thermally activated delayed fluorescence with longer-lived delayed components is realized from the F2 conformer. This approach may provide important clues for the design of high-energy organic phosphorescent materials.

Modulation of Delayed Fluorescence Guided by Conformational Effect-Mediated Thermally Enhanced Phosphorescence in Phenothiazines-Quinoline-Cl Conjugates.

Triplet energy harvesting via thermally activated delayed fluorescence (TADF) from pure organic systems has attracted great attention in organic light-emitting diodes, sensing, and photocatalysis. However, the realization of thermally enhanced phosphorescence (TEP)-guided efficient TADF with a high rate of reverse intersystem crossing (kRISC) still needs to be discovered. Herein, we report two phenothiazine-quinoline conjugates (P2QC, P2QMC) comprising two phenothiazine donors covalently attached to the chlorine-substituted quinolinyl acceptor. Spectroscopic analysis in conjunction with quantum chemistry calculations reveals that TEP in P2QC originated due to slow internal conversion from higher-lying triplet to lowest triplet (T2' → T1') of the quasi-axial (QA) conformer and TADF (kRISC = 1.44 × 108 s-1) originated from the quasi-equatorial (QE) conformer caused by a low singlet-triplet gap (ΔES1-T1 = 0.11 eV) and triplet energy transfer from QA to QE owing to the degenerate ground state of the conformers. In contrast, TADF (kRISC = 0.74 × 108 s-1) and dual phosphorescence under ambient conditions are observed in P2QMC. This study provides a sustainable guideline for developing efficient TADF emitters via conformation effects and energy transfer mechanisms.

A Case of Acute Extensive Viral Sinusitis Secondary to Acute Epstein Barr Virus.

Infectious mononucleosis (IM), the most common presentation of acute Epstein Barr virus (EBV) infection, typically presents with fever, pharyngitis and lymphadenopathy. We describe an unusual case of IM presenting as acute sinusitis. A 25 year-old male presented to the emergency department with worsening right frontal sinus pain along with fever, chills, and greenish nasal discharge for 3 weeks. Laboratory workup showed leukocytosis with high lymphocyte counts as well as transaminitis. Facial computerized tomography (CT) showed extensive right frontal, ethmoidal and maxillary sinusitis and antrochoanal polyp. The patient underwent endoscopy with drainage of purulent material and polyp removal. Unfortunately, cultures of the sample were not sent and bacterial infection could not be ruled out. Broad spectrum antibiotics were continued. Pathology of redundant tissue revealed large atypical lymphocytes with positive EBV-encoded RNA and lack of evidence of extranodal natural killer/T-cell (NK/T-cell) type lymphoma (ENKTCL). Tests for serum EBV IgM antibodies and EBV early Antigen antibodies were positive, indicating acute EBV infection. Lymphocytosis resolved along with significant clinical improvement at the 10-day follow up visit. Even though patient did receive antibiotics, multiple factors including isolated lymphocytosis, pathology positive for EBV with no neutrophilia were more suggestive of sinusitis caused by viral infection, EBV in this case. Lymphocytosis with fever and sore throat should prompt physicians to consider IM. There are no known reports in the literature of EBV as a causal organism for acute viral sinusitis. There are some studies relating EBV with ENKTCL. It is unknown whether this particular patient with a history of EBV sinusitis will be at high risk for nasal type lymphoma in the future. Further studies should be conducted to understand the pathogenesis and relationship between EBV and ENKTCL. LEARNING POINTS: Infectious mononucleosis (IM) can present with various atypical presentations. Consideration of IM should not be limited to people presenting with a triad of fever, lymphadenopathy and sore throat. Lymphocytosis with atypical symptoms should raise suspicion of infectious mononucleosis.No case has been reported of EBV as a causal organism for acute sinusitis. Association with EBV infection and chronic sinusitis or nasal polyp or extranodal NK/T cell lymphoma has been demonstrated but pathogenesis is poorly understood.Studies should be done on whether acute sinusitis secondary to EBV poses a risk for nasal type lymphoma.

A Rare Presentation of Myositis and Diffuse Alveolar Hemorrhage Associated With Disseminated Cryptococcus neoformans Infection.

Cryptococcosis is a fungal infection caused by species of the Cryptococcus genus which are commonly found in soil contaminated with bird feces, decaying wood, and tree hollows. It is usually seen in immunocompromised patients such as those with AIDS, with hematological malignancy, on immunosuppressive therapy, or after organ transplantation, and rare in immunocompetent hosts. The primary site of infection is usually the lung and the infection starts after inhalation of the pathogen and depending upon the host's immune response shows a different pattern of infection. Here we present a case report of a female in her late forties, who presented with two weeks of rash in her bilateral upper extremity, lower extremity, chest, and back along with arthralgia, myalgia, and proximal lower extremity weakness. Initial laboratory workup showed leukocytosis, elevated erythrocyte sedimentation rate, C-reactive protein, serum ferritin, and serum aldolase level with normal creatinine kinase. Rheumatological workups including ANA, ANCA, RF, C3, and C4 were normal. Magnetic resonance imaging of the right femur showed hyperintensity of the thigh and proximal calf musculature suggestive of muscle edema. A punch biopsy from the rash showed dyskeratosis with mild perivascular neutrophilic infiltrate. Steroid therapy and rituximab were started with some improvement. However, the patient developed respiratory distress and diffuse alveolar hemorrhage. Bronchoscopy was done and bronchoalveolar lavage fluid grew Serratia and Candida. The patient improved with antibiotic and antifungal therapy. However, the patient again developed respiratory distress and a new diffuse alveolar hemorrhage. A repeat bronchoscopy was done and the new bronchoalveolar lavage grew Cryptococcus neoformans. Blood cultures also grew Cryptococcus neoformans. The patient was started on amphotericin B and flucytosine. The patient initially improved and was transferred to the rehabilitation unit but ultimately her course was complicated by multiple infections and intubations and she unfortunately passed away.

Phenoxazine-Quinoline Conjugates: Impact of Halogenation on Charge Transfer Triplet Energy Harvesting via Aggregate Induced Phosphorescence.

Room-temperature phosphorescence (RTP) from organic compounds has attracted increasing attention in the field of data security, sensing, and bioimaging. However, realization of RTP with an aggregate induced phosphorescence (AIP) feature via harvesting supersensitive excited charge transfer triplet (3CT) energy under visible light excitation (VLE) in single-component organic systems at ambient conditions remains unfulfilled. Organic donor-acceptor (D-A) based orthogonal structures can therefore be used to harvest the energy of the 3CT state at ambient conditions under VLE. Here we report three phenoxazine-quinoline conjugates (PQ, PQCl, PQBr), in which D and A parts are held in orthogonal orientation around the C-N single bond; PQCl and PQBr are substituted with halogens (Cl, Br) while PQ has no halogen atom. Spectroscopic studies and quantum chemistry calculations combining reference compounds (Phx, QPP) reveal that all the compounds in film at ambient conditions show fluorescence and green-RTP due to (i) radiative decay of both singlet charge transfer (1CT) and triplet CT (3CT) states under VLE, (ii) energetic nondegeneracy of 1CT and 3CT states (1CT- 3CT, 0.17-0.21 eV), and (iii) spatial separation of highest and lowest unoccupied molecular orbitals. Further, we found in a tetrahydrofuran-water mixture (f w = 90%, v/v) that both PQCl (10-5 M) and PQBr (10-5 M) show concentration-dependent AIP with phosphorescence quantum yields (ϕP) of ∼25% and ∼28%, respectively, whereas aggregate induced quenching (ACQ) was observed in PQ. The phosphorescence lifetimes (τP) of the PQCl and PQBr aggregates were shown to be ∼22-62 µs and ∼22-59 µs, respectively. The ϕP of the powder samples is found to be 0.03% (PQ), 15.6% (PQCl), and 13.0% (PQBr), which are significantly lower than that of the aggregates (10-5 M, f w = 90%, v/v). Film (Zeonex, 0.1 wt %) studies revealed that ϕP of PQ (7.1%) is relatively high, while PQCl and PQBr exhibit relatively low ϕP values (PQCl, 9.7%; PQBr, 8.8%), as compared with that of powder samples. In addition, we found in single-crystal X-ray analysis that multiple noncovalent interactions along with halogen···halogen (Cl···Cl) interactions between the neighboring molecules play an important role to stabilize the 3CT caused by increased rigidity of the molecular backbone. This design principle reveals a method to understand nondegeneracy of 1CT and 3CT states, and RTP with a concentration-dependent AIP effect using halogen substituted twisted donor-acceptor conjugates.

Proliferative Verrucous Leukoplakia Revisited: A Retrospective Clinicopathological Study.

(1) Objective: To review the criteria proposed by Cerero-Lapiedra et al. and to retrospectively identify the under-diagnosed disease in patients diagnosed with proliferative verrucous leukoplakia. (2) Materials and methods: In this study, we included patients who were diagnosed with leukoplakia (histological label consistent with the clinical diagnosis, n = 95), and cases with a final diagnosis within the spectrum of proliferative verrucous leukoplakia (n = 110) as defined by Batsakis et al. We applied the criteria proposed by Cerero-Lepiedra et al. to screen for the possible cases of proliferative verrucous leukoplakia. (3) Results: Although many of our patients satisfied specific isolated criteria, only 11 cases satisfied specific combinations of the guidelines to satisfy a diagnosis of proliferative verrucous leukoplakia. However, due to the lack of follow-up data, the disease is not confirmed in these 11 cases. (4) Conclusion: A limited number of cases of proliferative verrucous leukoplakia were diagnosed using the criteria given by Cerero-Lapiedra et al. The true natural history of the disease could not be studied due to the lack of follow-up data. (5) Clinical relevance: Proliferative verrucous leukoplakia presenting as hyperkeratosis or mild epithelial dysplasia are often not followed up, and they subsequently transform into carcinoma. Thus, clinicians must be vigilant whenever they encounter leukoplakia, especially with multifocal presentations. In such cases, the follow-up data are the key to understanding the true nature of the disease entity.

Effect of head posture on tooth contacts in dentate and complete denture wearers using computerized occlusal analysis system.

PURPOSE: The purpose of the study was to assess and compare the occlusal contacts in dentate and edentulous patients wearing complete denture with varying head posture. MATERIALS AND METHODS: Ad hoc sampling of 30 subjects (15 dentate and 15 edentulous) based on inclusion and exclusion criteria was done. Subjects were divided into two groups: dentate and edentulous. Each group was further divided into two subgroups based on two head postures-upright 90° and ventroflexed 30°. For recording of every posture, a new sensor was used, and the subject was asked to clench on the sensor in maximum intercuspation position at the two head postures. RESULTS: Data were summarized as mean ± standard error and compared by Student's t-test using SPSS software (windows version 17.0 IBM corporation, New York, USA). A statistically significant correlation between head posture and contact area was found in dentate and denture wearers, i.e., tooth contact area varies with head posture. CONCLUSION: It was concluded that the occlusal contacts vary at different head posture in dentate as well as in denture wearers. With ventroflexion, the number of tooth contact decreased as compared to upright-erect position in both groups. Clinical implication - since the number of tooth contacts varies with varying head postures, it is recommended that the balancing of the contacts should be done at varying head postures.

A comparative study in the post-operative spine surgeries: Epidural ropivacaine with dexmedetomidine and ropivacaine with clonidine for post-operative analgesia.

BACKGROUND: Anaesthesia for spine surgeries is not only concerned with relieving pain during surgeries but also during the post-operative period. A prospective randomised study was carried out to evaluate the efficacy of epidural route and to compare the efficacy and clinical profile of dexmedetomidine and clonidine as an adjuvant to ropivacaine, in epidural analgesia with special emphasis on their quality of analgesia and the ability to provide the smooth post-operative course. METHODS: A total of 60 subjects, 33 were men and 27 were women between the age of 18 and 65 years of American Society of Anaesthesiologists (ASA) I/II class who underwent spine surgeries were randomly allocated into two groups, ropivacaine + dexmedetomidine (RD) and ropivacaine + clonidine (RC), comprising 30 patients each. Group RD received 20 ml of 0.2% ropivacaine and 1 µg/kg of dexmedetomidine while group RC received 20 ml of 0.2% ropivacaine and 2 µg/kg of clonidine through the epidural catheter. Onset of analgesia, time of peak effect, duration of analgesia, cardiorespiratory parameters, side-effects and need of rescue intravenous (IV) analgesics were observed. RESULTS: The demographic profile and ASA class were comparable between the groups. None of the patients needed rescue analgesics in either group. Group RD had early onset, early peak effect, prolonged duration and stable cardiorespiratory parameters when compared with group RC. The side-effects profile was also comparable with a little higher incidence of nausea and dry mouth in both groups. CONCLUSION: Epidural route provided acceptable analgesia in spine surgeries and avoided the need of IV analgesics in either group. Dexmedetomidine is a better neuraxial adjuvant compared with clonidine for providing early onset and prolonged post-operative analgesia and stable cardiorespiratory parameters.

A SEM evaluation of dentinal adaptation of root canal obturation with GuttaFlow and conventional obturating material.

OBJECTIVE: The aim of this in-vitro study was to compare dentinal adaptation of conventional obturating material and GuttaFlow in young permanent teeth of child patients. MATERIALS AND METHODS: Ten young permanent anterior teeth with closed foramen were selected for the study. Root canal preparations were carried out using a step back technique. The canal was alternately irrigated with 5.25% sodium hypochlorite solution and 17% EDTA and normal saline. After root canal preparation specimens were randomly divided into two groups (n=5). GROUP "A": Obturated with zinc-oxide eugenol sealer and gutta-percha cone using cold lateral obturation technique. GROUP "B": Obturated with GuttaFlow as per the manufacturer's instruction. The teeth were split into two halves. Five randomly chosen longitudinal split teeth samples each from Group "A" and Group "B" was observed under scanning electron microscope to access the interface between obturating material and dentin at the level of 2 mm from the apex. RESULTS: On statistical analysis the dentinal adaptation (µm) of Group A was observed with a mean of 0.52 and standard deviation 0.15, while the value of mean and standard deviation were noted 0.12 and 0.02 for Group B. The "t" value on comparison of Group A and Group B is 5.79 with "P " value of <0.001, which is highly significant. CONCLUSION: From result of the study it can be concluded Group B samples showed significantly superior seal when compared with Group A. Complete seal was not observed in any of Group A samples.