Aims: Older adults are vulnerable to medication-related harm mainly due to high use of medications and inappropriate prescribing. This study aimed to investigate the associations between inappropriate prescribing and number of medications identified at discharge from geriatric rehabilitation with subsequent post-discharge health outcomes. Method: REStORing health of acutely unwell adulTs (RESORT) is an observational, longitudinal cohort study of geriatric rehabilitation inpatients. Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) were measured at acute admission, and at admission and discharge from geriatric rehabilitation, using version 2 of the STOPP/START criteria. Results: 1890 patients (mean age 82.6 ± 8.1 years, 56.3 % females) were included. The use of at least 1 PIMs, or PPOs at geriatric rehabilitation discharge were not associated with 30-day and 90-day readmission and 3-month and 12-month mortality. Central nervous system (CNS)/psychotropics and fall risk PIMs were significantly associated with 30-day hospital readmission (adjusted odds ratio (AOR) 1.53; 95%CI 1.09─2.15), and cardiovascular PPOs with 12-month mortality (AOR 1.34; 95%CI 1.00─1.78). Increased number of discharge medications was significantly associated with 30-day (AOR 1.03; 95%CI 1.00─1.07) and 90-day (AOR 1.06; 95%CI 1.03─1.09) hospital readmissions. The use and number of PPOs (including vaccine omissions) were associated with reduced independence in instrumental activities of daily living scores at 90-days post geriatric rehabilitation discharge. Conclusion: The number of discharge medications, CNS/psychotropics and fall risk PIMs were significantly associated with readmission, and cardiovascular PPOs with mortality. Interventions are needed to improve appropriate prescribing in geriatric rehabilitation patients to prevent hospital readmission and mortality.
Organic luminogens with persistent room temperature phosphorescence (RTP) have drawn tremendous attentions due to their prom-ising potentials in optoelectronic devices, information storage, biological imaging, and anti-counterfeiting. In this work, six triazatrux-ene-based lumiogens with different peripheral substituents and configurations are synthesized and systematically studied. The results show that their fluorescence quantum yields in solid states range from 15.73% to 37.58%. Dispersing the luminogens as guest into the host (PPh3) could turn on the persistent RTP, where PPh3 acts as not only a rigid matrix to suppress the non-radiative transitions of the guest, but also provides energy transfer channels to the guest. The maximum phosphorescence efficiency and the longest lifetime could reach 29.35% and 0.99 s in co-crystal films of 6-TAT-CN/PPh3 and 5-TAT-H/PPh3, respectively. Moreover, these host-guest co-crystalline films exhibit great potentials in advanced dynamic data encryption and anti-counterfeiting. This work deepens the insight for low cost, halogen-free, and facile fabrication of all-organic persistent RTP materials.
A methodology is proposed to aid parameter estimation in fundamental models of pharmaceutical processes. This methodology addresses situations with insufficient data to reliably estimate all parameters, when the estimation is complicated by uncertain independent variables. The proposed method uses an augmented sensitivity matrix to rank the combined set of parameters and uncertain inputs from most estimable to least estimable. An updated mean-squared-error criterion is then used to determine the appropriate parameters and inputs that should be estimated, based on the ranked list. A model for one step in a batch pharmaceutical production process with an uncertain initial reactant concentration is used to illustrate the method, revealing that the initial reactant concentration in each batch should be estimated along with three out of six model parameters. Non-estimable parameters are fixed at their initial values to prevent overfitting. The method will aid error-in-variables parameter estimation in many situations involving limited data.
New-onset pemphigus after COVID-19Yihang Xie1 Mei Yang1 Peimei Zhou1* Jiaming Fan1 Sijie Zhou11.Department of Dermatovenereology, Chengdu Second People’s Hospital, Chengdu, China* Corresponding Author: firstname.lastname@example.org head: pemphigus after COVID‐19The category of the article: LetterKeywords: COVID‐19, pemphigusManuscript word count: 690 wordsThe number of figures: 2The number of tables: 0The number of references: 8Correspondence to: Peimei Zhou, M.D, Ph.D., Department of Dermatovenereology, Chengdu Second People’s Hospital, Qingyun Street, Chengdu, 610041, China.Tel: +86 18908176315; E-mail:email@example.comFull conflict of interest statement: Y. Xie, and my co-authors have no conflict of interest to declare.Ethics statement: The patient has consented to publish this information.Data availability statement: Data sharing does not apply to this article as no new data were created or analyzed in this study.Funding sources: noneDear Editor,Cutaneous manifestations of coronavirus disease (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; family Coronaviridae, genus Betacoronavirus, subgenusSarbecovirus ), have been increasingly reported. SARS-CoV-2 infection is multisystemic and leads to potentially detrimental effects on various organs. Maculopapular, urticarial, vesicular, livedoid, and Chilblain-like lesions (CBLL) have been commonly reported to be associated with COVID-191. Here, we encountered an intriguing case of pemphigus that developed after COVID-19 infection.A 73-year-old male presented with a 42-day history of pruritic flaccid blisters that arose on the trunk and both upper limbs on normal and erythematous skin. Cutaneous lesions started 3 days after the positive reverse transcription polymerase chain reaction (RT-PCR) test diagnostic for SARS-CoV-2. He denied any history of systemic diseases, medication, and medicine or food allergies, and had not used any medication before symptom onset. The patient had first been diagnosed with allergic dermatitis caused by COVID-19 at another hospital and was prescribed oral prednisone (8 mg once daily for 4 days). The patient reported no new blisters, but the erythema did not fade; therefore, he visited our hospital. Physical examination revealed cutaneous lesions on the trunk and both upper limbs without mucosal involvement and scattered superficial blisters that developed into crusted erosions on an erythematous base(Figure1 A-D). Laboratory examination revealed normal white cell count (8.63 Ã–109/L; normal 3.5-9.5 Ã–109/L) with eosinophilia (6%; normal 0.5%-5.0%). Desmoglein (Dsg) 1 antibody levels were > 150 U/mL (positive: > 20), while Dsg3, BP(bullous pemphigoid)180, and BP230 antibody levels were within normal ranges. Other laboratory tests including RT-PCR targeting SARS-CoV-2, immunoglobulin, erythrocyte sedimentation rate, the spectrum of antinuclear antibodies, and T-spot were negative or normal. Chest and abdominal computed tomography revealed chronic inflammatory changes but no obvious tumors. Histological analysis of an incisional cutaneous biopsy taken from the patient’s abdomen showed subcorneal blister formation, acantholytic cells within the blister, and marked spongiotic edema in the spongiosa layer that had mixed inflammatory infiltrate with eosinophils, leukomonocytes, and neutrophils(Figure2A). Direct immunofluorescence (DIF) showed deposition of intracellular IgG and C3 in subepidermal 2/3 interspinous cells, though was negative for IgA and IgM, confirming pemphigus(Figure2B,C). Considering the good response to hormone treatment, the patient continued oral prednisone at 8 mg once daily along with the use of topical corticosteroids. Symptoms were completely absent after 3 weeks(Figure1 E-F).An increasing number of studies on cutaneous manifestations of COVID-19 have been reported; however, knowledge is still lacking on the common skin manifestations of this disease. Nonspecific cutaneous manifestations due to SARS-CoV-2 infection have also been reported, such as immune thrombocytopenic purpura (ITP), dengue-like exanthem, pityriasis rosea-like eruptions, acral ischemia, mucositis, dusky lesions, and bullae2.3.4. We searched all relevant articles and found only two cases of pemphigus vulgaris induced by COVID-19. In the case presented here, we realized that COVID-19 may be responsible for the rash eruption, possibly due to an inflammatory reaction5. The onset time of the rash was similar to that in the cases of pemphigus previously reported by De Medeiros5 and Mohaghegh F6 (within 1.5 months). In our case, although direct immunofluorescence showed subepidermal 2/3 deposition, we still diagnosed pemphigus foliaceus in combination with the pathological presentation, indirect immunofluorescence, and good treatment outcome. We speculate that the reason why direct immunofluorescence showed subepidermal 2/3 deposition may be the marked sponge edema of the epidermis, which may lead to a discontinuity of acantholysis, resulting in leakage of Dsg1 into the deeper epidermis.Pemphigus is defined as a group of rare mucocutaneous autoimmune diseases. Its etiology is unknown, though there are studies on autoimmune etiology which is believed to be related to stimulation by certain drugs, ultraviolet radiation, and malignant tumors; these induce autoimmune reactions by making the adhesive substances between the spiny cell layers become autoantigens7. It is rarely considered, however, that viral infections might cause pemphigus. The ability of SARS-CoV-2 to induce a hyper-stimulated immune state was discovered at the beginning of the pandemic8. As an instrumental trigger of autoimmunity, SARS-CoV-2 infection could be a trigger for autoimmune reactions, possibly through more than one mechanism. Because of this, all factors should be considered in any patient presenting with new-onset or exacerbating cutaneous reactions.
Over three years, humans have experienced multiple rounds of global transmission of SARS-CoV-2 and its variants. In addition, the widely used vaccines against SARS-CoV-2 involve multiple strategies of development and inoculation. Thus, the acquired immunity established among humans is complicated, and there is a lack of understanding within a panoramic vision. Here, we provide the special characteristics of the cellular and humoral responses in 2-year convalescents after inactivated vaccines, in parallel to vaccinated COVID-19 naïve persons and unvaccinated controls. The decreasing trends of the IgG, IgA, and NAb, but not IgM of the convalescents were reversed by the vaccination. Both cellular and humoral immunity in convalescents after vaccination were higher than the vaccinated COVID-19 naïve persons. Notably, inoculation with inactivated vaccine fueled the NAb to BA.1, BA.2, BA.4, and BA.5 in 2-year convalescents, much higher than the NAb during 6 months and 1 year after symptoms onset. And no obvious T cell escaping to the S protein was observed in 2-year convalescents after inoculation. The study provides insight into the complicated features of human acquired immunity to SARS-CoV-2 and variants in the real world, indicating that promoting vaccine inoculation is essential for achieving herd immunity against emerging variants, especially in convalescents.
Some of the most vexing problems of deep level relationship that remain in angiosperms involve the superrosids. The superrosid clade contains a quarter of all angiosperm species, with 18 orders in three subclades (Vitales, Saxifragales and core rosids) exhibiting remarkable morphological and ecological diversity. To help resolve deep-level relationships, we constructed a high-quality chromosome-level genome assembly for Tiarella polyphylla (Saxifragaceae) thus providing broader genomic representation of Saxifragales. Whole genome microsynteny analysis of superrosids showed that Saxifragales shared more synteny clusters with core rosids than Vitales, further supporting Saxifragales as more closely related with core rosids. To resolve the ordinal phylogeny of superrosids, we screened 122 single copy nuclear genes from genomes of 36 species, representing all 18 superrosid orders. Vitales were recovered as sister to all other superrosids (Saxifragales + core rosids). Our data suggest dramatic differences in relationships compared to earlier studies within core rosids. Fabids should be restricted to the nitrogen-fixing clade, while Picramniales, the Celastrales-Malpighiales (CM) clade, Huerteales, Oxalidales, Sapindales, Malvales and Brassicales formed an “expanded” malvid clade. The Celastrales-Oxalidales-Malpighiales (COM) clade (sensu APG IV) was not monophyletic. Crossosomatales, Geraniales, Myrtales and Zygophyllales did not belong to either of our well-supported malvids or fabids. There is strong discordance between nuclear and plastid phylogenetic hypotheses for superrosid relationships; we show that this is best explained by a combination of incomplete lineage sorting and ancient reticulation.
Morphological identification of cnidarian species can be difficult throughout all life stages due to the lack of distinct morphological characters. Moreover, in some cnidarian taxa genetic markers are not fully informative, and in these cases combinations of different markers or additional morphological verifications may be required. Proteomic fingerprinting based on MALDI-TOF mass spectra was previously shown to provide reliable species identification in different metazoans including some cnidarian taxa. For the first time, we tested the method across four cnidarian classes (Staurozoa, Scyphozoa, Anthozoa, Hydrozoa) and included different scyphozoan life-history stages (polyp, ephyra, medusa) into our dataset. Our results revealed reliable species identification based on MALDI-TOF mass spectra across all taxa with species-specific clusters for all 23 analyzed species. In addition, proteomic fingerprinting was successful for distinguishing developmental stages, still by retaining a species specific signal. Furthermore, we identified the impact of different salinities in different regions (North Sea and Baltic Sea) on proteomic fingerprints to be negligible. In conclusion, the effects of environmental factors and developmental stages on proteomic fingerprints seem to be low in cnidarians. This would allow using reference libraries built up entirely of adult or cultured cnidarian specimens for the identification of their juvenile stages or specimens from different geographic regions in future biodiversity assessment studies.
RATIONALE: Sample preparation is one of the most crucial steps for MALDI mass spectrometry imaging (MALDI-MSI). The scientists beginning their adventure with this technique may be overwhelmed by the variety of matrices, solvents, concentrations, the ways of their applications, and the lack of widely available knowledge about the influence of these parameters on the results. Here we would like to present our experiences with detailed aspects of matrices deposition, hopefully helpful for the scientific community. METHODS: In our article, we have tested several MALDI matrices applied by the SunCollect® system: wet-interface matrix deposition in the context of lipids analysis. Among them: 2,5-dihydroxybenzoic acid (DHB), norharmane, N-(1-naphthyl) ethylenediamine dihydrochloride (NEDC), 9-aminoacridine (9AA). We have optimized the number of matrix layers and nozzle settings in terms of spectra intensity and the overall quality of obtained ion maps. RESULTS: Our research presents the influence of the number of matrix layers and nozzle settings on the results and allows for choosing the optimal parameters for the analyses. In positive ionization mode, DHB matrix could be chosen as the first selection. In the negative ionization mode, DAN matrix produces higher peak intensity in a lower mass range and seems to provide more information than 9AA. We recommended NEDC for particular tasks such as glucose analysis. Comparably to remaining matrices, norharmane significantly changes received ion maps. CONCLUSIONS: Dealing with such a great amount of data allows us to notice an interesting conclusion: the obtained ion picture for a particular ion could differ dramatically with changing the matrix, the solvent composition, or even the number of matrix layers. This must be considered when interpreting the result and forces us to compare the results obtained with different matrices with extreme caution.
Rational: Organisms that grow a hard carbonate shell or skeleton, such as foraminifera, corals or molluscs, incorporate trace elements into their shell during growth that absorbs the environmental change and biological activity they experienced. These geochemical signals locked within the carbonate are archives used in proxy reconstructions to study past environments and climates, to decipher taxonomy of cryptic species and to resolve evolutionary responses to climatic changes. Methods: Here we use a laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) as a time resolved acquisition to quantify the elemental composition of carbonate shells. We present the LABLASTER (Laser Ablation BLASt Through Endpoint in R) package, which imports a single time resolved LA-ICP-MS analysis, then detects when the laser has ablated through the carbonate as a function of change in signal over time, and outputs key summary statistics. We provide two worked examples within the package: a planktic foraminifera and a tropical coral. Results: We present the first R package that improves signal: noise ratios in data reduction workflows by automating the detection of when the laser has ablated through a sample using a smoothed time-series and subsequent removal of off-target data points. The functions are flexible and adjust dynamically to enhance the signal: noise ratio of the desired geochemical target. Visualisation tools for manual validation are also included. Conclusions: LABLASTER increases transparency and repeatability by algorithmically identifying when the laser has either ablated fully through a sample or across a mineral boundary and is thus no longer documenting a geochemical signal associated with the desired sample. LABLASTER’s focus on better data targeting means more accurate extraction of biological and geochemical signals.
Isochromanone is the core structure of many bioactive compounds. Direct oxidation of isochromans is one of leading methods for the construction of isochromanones, while most established processes remain suffering from the use of environmental unfriendly metal oxidants, harsh reaction conditions, and the difficulty in catalyst recycling and production separation. Herein, we report a convenient, cost-effective, and green method for the synthesis of high-value added isochromanones via isochroman oxidations with O2 by a novel heterogeneous vanadium cluster catalyst (Cat.1) under mild conditions. This reaction protocol demonstrates high catalytic activity with good catalyst recyclability and reusability for a wide scope of substrates.
It is found that there are two piecewise functions satisfy the conditions in the impulsive fractional partial differential system (IFrPDS), which deduce that the three different integral solutions of the IFrPDS given in the cited papers are inappropriate. Next, by applying two limit properties of the IFrPDS and the properties of piecewise function, the new formula of solution of the IFrPDS is discovered that is the integral equation with an arbitrary continuously differentiable function of t on [0 ,c] to reveal the non-uniqueness of the IFrPDE’s solution. Finally, an example is provided to expound the computation of the solution of the IFrPDS.
Listening effort can be defined as a measure of cognitive resources used by listeners to perform a listening task. Several methods have been proposed to assess listening effort, but the reliability of these methods has not yet been thoroughly established, which is necessary before using them in research or clinical settings. This study included 32 participants who performed speech-in-noise tasks in two sessions (separated approx. 1 week apart) by listening to Sentences and Word lists presented at different signal-to-noise ratios (-9, -6, -3, and 0 dB). We assessed the test-retest reliability of the self-reported measure of listening effort and frontal midline theta (Fmθ) power, which has been proposed as a neural correlate of listening effort. The reliability of the percentage of correct words was also examined. Relative and absolute reliability was evaluated using intraclass correlation coefficients (ICC) and Bland-Altman analysis, respectively. The standard error of measurement (SEM) and the smallest detectable change (SDC) were also assessed. Overall, the reliability analysis revealed an acceptable between-session variability for the correct words and effort rating. However, Fmθ power showed high variability, which brings into question its use as a reliable correlate of listening effort.
Auditory processing and the complexity of neural activity can both indicate residual conscious-ness levels and differentiate between states of arousal. However, how measures of neural signal diversity, or complexity, manifest in evoked activity, and, more generally, how the electrophys-iological characteristics of auditory responses change in states of reduced consciousness, re-main under-explored. Here, we tested the hypothesis that measures of neural complexity and the spectral slope would discriminate stages of sleep not only in spontaneous EEG, but also in auditory-evoked responses. High-density EEG was recorded in 21 participants to determine the spatial relationship between these measures, and between spontaneous and auditory-evoked signals. Results showed that the complexity and the spectral slope in the 2-20 Hz range dis-criminated between sleep stages and had a high correlation in sleep. In wakefulness, complexity was strongly correlated to the 20-40 Hz spectral slope. Auditory stimulation resulted in reduced complexity in sleep compared to spontaneous activity and modulated the spectral slope in wake-fulness. These findings demonstrate the persistence of electrophysiological markers of arousal during both spontaneous and evoked EEG activity and have direct applications to studies using auditory stimulation to probe neural functions in states of reduced consciousness.
This paper presents a low dropout regulator (LDO) with a wide input voltage range and high power supply rejection (PSR) for hall sensor front-end circuits, which is fabricated with a 0.18 μm BCD process. A topology in which a closed-loop charge pump biases the gate of two-stage cascode NMOS pass transistors is proposed to increase immunity to Electro-Magnetic Interference (EMI) capability for automotive applications. Furthermore, a power-down protection circuit is proposed to maintain the reliability of the system, and a novel implementation of the charge pump unit is presented to improve the influence of the body effect. Detailed derivation regarding the analyses of the simplified small-signal model of the closed-loop charge pump, the loop stability, and the PSR at various frequency bands is given. Simulation and measurement results show that the proposed LDO can operate with the input voltage from 5 V to 40 V, providing up to 60 mA current drive capability, and its minimum operating voltage is 2.5 V with 10 mA load capacity. Moreover, results verify that simulated PSR is better than -81 dB at 1 kHz, and measured PSR is better than -32 dB at 10 MHz. The results confirm that the obtained parameters of line and load regulations are significantly improved to 1.86 mV/V and 1.75 mV/mA, respectively.
Mechanical specimens of rock-like materials were prepared from cement, gypsum, quartz sand and water. After the specimens were formed, they were immersed in acid solutions of pH=2 and pH=4 for 60d and 90d respectively, and uniaxial compression tests were carried out before and after immersion to obtain mechanical parameters.Quantification of the extent of degradation of mechanical parameters and introduction of acid corrosion damage variables.Based on the Lemaitre strain equivalence principle, the Weibull distribution statistical damage model for rock-like micro-fractures was combined with a correction for damage variables that takes into account the effect of residual strength to derive a damage constitutive model under acid corrosion.The theoretical damage constitutive curves were compared with the experimental curves to analyse the applicability of the constitutive equation.The results show that after corrosion by the acid solution, the initial compression-density portion of the stress-strain curve of the specimen becomes longer and the elastic deformation phase becomes shorter,the elastic modulus, peak stress and residual strength of the specimen all decrease, and the final strain of the compression-density portion, final elastic strain, peak strain and residual strength strain values all increase,the longer the maintenance time and the more acidic the solution, the more significant the above characteristics are.Comparing the theoretical and experimental curves, the damage constitutive model, which includes acid damage and residual strength corrections, agrees well in the elastic, plastic and post-peak phases.
Hepatosplenic T-cell lymphoma mimics various infectious diseases, immunological conditions, and other malignancies. Because there is no lymph node involvement, it causes difficulty in diagnosing lymphoma and significant delays in the initiation of treatment. This type of lymphoma should be considered in the presence of hepatosplenomegaly and cytopenia.
Variation in Location of the Distobuccal Root Canal in a permanent Maxillary Second Molar: A Case Report and Literature ReviewABSTRACTThis case report describes the unusual location of the distobuccal root canal in a maxillary second molar with root fusion. On access opening, three distinct root canal orifices, the mesiobuccal canal, palatal canal, and a third orifice closer to the palatal canal, were seen, giving an illusion of an additional palatal canal. An attempt was made to search for the distobuccal canal in its usual position, leading to the gouging of the pulp chamber floor. An intra-operative limited field of view cone-beam computed tomography (CBCT) revealed the root orifice adjacent to the palatal canal was the distobuccal canal. CBCT also revealed fusion of both the buccal and palatal roots in the root’s coronal and middle third region, but they were not fused apically.Keywords: cone-beam computed tomography, distobuccal, fused roots, maxillary second molar, variation.INTRODUCTIONThe root canal system is highly complex and variable.1Numerous case reports and earlier studies have reported variations in maxillary molars.2-4 Variations have been mostly reported in the form of extra canals being present. However, Zhanget al., in an in-vitro study, found maxillary second molars to have more variations than the first molars.5 Most of the earlier studies have focused on the Mesiobuccal (MB) root of the maxillary first molar, as it frequently has two root canals with variations in the root canal pattern.6,7The case reports published in the literature pertaining to the variations in maxillary second molar are most frequently in relation to the alterations in the number of roots or root canals. Kottor et al. reported a case of a maxillary second molar with five roots and five separate canals in each of these roots.8 In contrast, Ahuja et al. reported a case of a maxillary second molar with a single root and single canal.9Regarding the distobuccal (DB) root canal, variations have been reported in the form of one additional canal (DB2) being present or fused with the MB canal. Fusion can also occur between one or both the buccal roots with the palatal (P) root.10-14 Fusion of the roots is more common in maxillary second molars, which could result in complete or partial fusion of the root canals.15,16For successful endodontic treatment, clinicians should be aware of the variations in the number of roots and root canals and the peculiar or eccentric location of root canals as described in this case report. This case report highlights the anatomic variation of the distobuccal root canal in a maxillary second molar and its management with the aid of an intra-operative limited field of view (FOV) Cone-beam computed tomography (CBCT), along with a literature review of variations reported in distobuccal roots and root canals in human maxillary second molar. The case presentation is based on the Preferred Reporting Items for Case reports in Endodontics (PRICE) 2020 guidelines.17CASE PRESENTATIONA 34-year-old male patient reported to the department with a chief complaint of pain in his upper left back tooth for the past ten days. History revealed an intermittent, localized throbbing type of pain, occurring during the night and aggravated during mastication. The patient’s medical history was non-contributory. Clinical intra-oral examination revealed deep occlusal caries in the maxillary left second molar (27) with tenderness to percussion. The tooth had an old amalgam restoration on the occlusal surface. The tooth mobility was within physiological limits, and the gingival attachment apparatus was normal. Thermal and electric pulp testing (Parkel Electronics Division, Farmingdale, New York, USA) elicited a negative response. The preoperative intraoral periapical radiograph (IOPA) revealed occlusal radiolucency involving pulp space with no periapical radiolucency (Figure 1A, 1B). Extra orally, no swelling was noticed. From the clinical and radiographic findings, a diagnosis of pulpal necrosis with symptomatic apical periodontitis was made, and endodontic treatment was initiated after obtaining consent from the patient.The tooth was anesthetized by using 1.8 ml (30 mg) of 2% lidocaine containing 1:200,000 epinephrine (AstraZeneca Pharma India Ltd., Bengaluru, India). Isolation was done using a rubber dam (Coltene Whaledent, Inc., Ohio, USA), and access opening was initiated using an endo access bur (#1) in high speed (Dentsply Sirona, Tulsa, USA) under a dental operating microscope (Prisma DNT Microscope, Labo America, Inc., California, USA). The pulp chamber floor examination with a DG-16 endodontic explorer (Hu-Friedy, Chicago, USA) revealed three distinct root canal orifices, the MB canal, and P canal, and another orifice in close approximation to the P canal, giving an illusion of an additional P canal (Figure 1C). An attempt was made to search for the DB canal in its usual position, but without success, this led to the gouging of the floor in that area (Figure 1C). As the DB canal was not identified in its usual location and a canal orifice was seen unusually placed between the buccal and P canal, an intra-operative limited FOV-CBCT was taken after obtaining consent from the patient. CBCT images of the maxillary second molar revealed fusion of both the buccal and palatal roots in the coronal and middle third region of the root, but apically they were separate. CBCT images confirmed the canal adjacent to the P orifice to be the DB canal. Even though the roots were fused partially, the canals remained separate (Figure 2A to 2F). The coronal section of the tooth in the CBCT scan also revealed early periapical radiolucency in the palatal root, which was not evident in the two-dimensional IOPA (Figure 2D). Working length was determined using IOPA and an electronic apex locator (Root ZX; Morita, Tokyo, Japan). Shaping and cleaning were performed using ProTaper Gold (Dentsply Maillefer, Ballaigues, Switzerland) and the crown-down technique. The MB and DB canals were enlarged to ProTaper F2 (25/08), and the P canal was enlarged until ProTaper F3 (30/09). The instrumentation was performed using 2.5% sodium hypochlorite solution and normal saline. Final irrigation was performed with 2.5 % sodium hypochlorite solution (Sisco Research Laboratories Pvt. Ltd., Mumbai, India), 17% EDTA (Prime Dental Product Pvt Ltd, Mumbai, India), and normal saline. The canals were medicated with Calcium hydroxide paste (Calcicur, VOCO, Cuxhaven, Germany) using a lentulo spiral (Dentsply Maillefer, Ballaigues, Switzerland), and the access cavity was sealed with Cavit (3M ESPE Dental Products, St Paul, MN, USA). The patient was asymptomatic during recall after 2 weeks. Calcium hydroxide was removed, and obturation was done by single cone obturation technique using F2 and F3 Gutta-percha (Dentsply Maillefer, Ballaigues, Switzerland) and AH plus resin sealer (Dentsply Maillefer Company, Tulsa, OK, USA) (Figure 3A). The access cavity was sealed using resin composite (Z-100; 3M ESPE Dental Products, St Paul, MN). The patient was asymptomatic during a follow-up period of 1 year (Figure 3B).DISCUSSIONRoot fusion occurs due to disturbance in Hertwig’s epithelial root sheath during developmental stages. It can also occur due to fusion in the furcation area or deposition of cementum over time.18 Root fusion is a common entity in maxillary second molars compared to the first molars.4 Fusion of roots can result in partial or complete fusion of the root canals and can lead to intra-canal communications or canal divisions that are challenging to shape and clean.19In this case report, the root canals remained separate without any communication. Based on Zhang et al. classification for fused roots in maxillary second molars, this tooth can be classified as a Type 5 pattern where the P root fused with MB and DB root.15 According to the recent classification of anomalies by Ahmed et al. , it can be classified as (RF5)327MB/DB/P.20In maxillary second molars, the three roots are grouped closer together, making the orifices form a flat triangle to almost a straight line. DB orifice is closer to the MB orifice and is usually located in the midpoint when a line is drawn from the MB to P orifices (Figure 4A).21 However, there are few cases reports on the variation of DB roots or root canals (Table 1). These variations are in the form of an extra root or root canal present close to the main DB canal. Variations in the DB root canals in literature are also present in the form of partial or complete fusion to either MB or P canals forming C-shaped canals or fusions leading to double or single-rooted maxillary second molars.8-14 These case reports also point to the fact that when a root canal orifice deviates from its actual position, there always is a need for careful inspection and exploration for possible additional canals.In the present case report, the search for the DB canal in its usual position led to the gouging of the pulpal floor. The intraoperative CBCT revealed that the roots were fused in the coronal and middle third, with the DB root placed palatally. Hence, the peculiar canal located just buccal to the P root canal orifice was the DB canal, which seemed to give an illusion of an additional P canal (Figure 4B). All three root canals also showed Vertucci Type I root canal pattern with no intra-canal communications with each other. To the best of our knowledge, no case report on such peculiarity in the position of the DB canal orifice has yet been published in the literature.In an earlier study by Han et al . done in the Chinese population, the average distance between the DB and P canals was 3-5mm, and between MB and DB canals was 1.5-3mm.22 The distance between the DB and P orifice was only 0.6mm, and between DB and MB orifice was 3.9mm in the present case when calculated using the measuring tool in the CBCT software (Planmeca Romexis version 5.2.0R). The smaller mesiodistal diameter of 8mm of the involved teeth, partial root fusion, and/or palatal positioning of the DB root could have been the possible reason(s) for the unusual position of the DB canal in the current case report.The spatial relationship between the roots and adjacent anatomical structures and the position and shape of anatomical structures inside the root to be treated is often difficult to assess using a conventional 2-D radiograph.23 Using CBCT in such complex cases enables us to understand the internal root canal anatomy better.24CONCLUSION Unusual root canal morphology of the maxillary molars is invariably a norm, and it should be visualized during the planning phase of endodontic treatment. This will help the treating clinician deliver a customized treatment plan to the patient precisely. This case report highlights the variability of the root morphology. It further describes the exact variation in the root canal system of a maxillary second molar, i.e., DB root canal close to the P root canal orifice with partially fused roots. An intraoperative CBCT aided in the better understanding and management of this particular root canal anatomy, followed by the precise execution of the treatment plan.ACKNOWLEDGMENT: None.FUNDING INFORMATION: None.CONFLICT OF INTEREST STATEMENT: The authors declare no conflict of interest related to this publication. This work did not receive any funding.DATA AVAILABILITY STATEMENT: Data related to this paper are available for consultation if requested.PATIENT CONSENT STATEMENT: A written informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy and is in the author’s possession.REFERENCESVertucci FJ. Root canal anatomy of the permanent human teeth. 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