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. Oral Surg Oral Med Oral Pathol . 1984;58(5):589-599. doi:10.1016/0030-4220(84)90085-9.Martins JNR, Alkhawas MAM, Altaki Z, Bellardini G, Berti L, Boveda C, et al . Worldwide analyses of maxillary first molar second mesiobuccal prevalence: A multicenter cone-beam computed tomographic study. J Endod . 2018;44(11):1641-9.e1. doi:10.1016/j.joen.2018.07.027.Martins JN, Mata A, Marques D, Anderson C, Caramês J. Prevalence and characteristics of the maxillary C-shaped molar. J Endod . 2016;42(3):383-389. doi:10.1016/j.joen.2015.12.013.Martins JN, Mata A, Marques D, Caramês J. Prevalence of root fusions and main root canal merging in human upper and lower molars: A cone-beam computed tomography in vivo study. J Endod . 2016;42:900-908. doi:10.1016/j.joen.2016.03.005.Zhang R, Yang H, Yu X, Wang H, Hu T, Dummer PM. Use of CBCT to identify the morphology of maxillary permanent molar teeth in a Chinese subpopulation. Int Endod J . 2011;44:162-169. doi:10.1111/j.1365-2591.2010.01826.x.Studebaker B, Hollender L, Mancl L, Johnson JD, Paranjpe A. The incidence of second mesiobuccal canals located in maxillary molars with the aid of cone-beam computed tomography. J Endod . 2018;44(4):565-570. doi:10.1016/j.joen.2017.08.026.Martins J. Second mesiobuccal root canal in maxillary molars-A systematic review and meta-analysis of prevalence studies using cone beam computed tomography. Arch Oral Biol.  2019;24:104589. doi:10.1016/j.archoralbio.2019.104589.Kottoor J, Hemamalathi S, Sudha R, Velmurugan N. Maxillary second molar with 5 roots and 5 canals evaluated using cone beam computerized tomography: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod . 2010;109(2):e162-165. doi:10.1016/j.tripleo.2009.09.032.Ahuja P, Ballal S, Velmurugan N. Endodontic management of maxillary second molar with a single root and a single canal diagnosed with cone-beam computed tomography scanning. Saudi Endod J.2012;2(2):100-103.doi:10.4103/1658-5984.108162.Fahid A, Taintor JF. Maxillary second molar with three buccal roots.J Endod. 1988;14(4):181-183. doi:10.1016/S0099-2399(88)80261-9.Suresh M, Karthikeyan K, Mahalaxmi S. Maxillary second molar with fused root and six canals- A case report. J Clin Diagn Res.2017;11:ZD35-ZD37. doi:10.7860/JCDR/2017/25005.9743.Zeng C, Shen Y, Guan X, Wang X, Fan M, Li Y. Rare root canal configuration of bilateral maxillary second molar using cone-beam computed tomographic scanning. J Endod. 2016;42(4):673-677. doi:10.1016/j.joen.2015.12.028.Zmener O, Peirano A. Endodontic therapy in a maxillary second molar with three buccal roots. J Endod. 1998;24(5):376-377. doi: 10.1016/s0099-2399(98)80138-6 .Saeed Asgary. Endodontic treatment of a maxillary second molar with developmental anomaly: A case report. Iran Endod J.2007;2(2):73-76.Zhang Q, Chen H, Fan B, Fan W, Gutmann JL. Root and root canal morphology in maxillary second molar with fused root from a native Chinese population. J Endod . 2014;40(6):871-875. doi:10.1016/j.joen.2013.10.035.Ordinola-Zapata R, Martins JNR, Bramante CM, Villas-Boas MH, Duarte MH, Versiani MA. Morphological evaluation of maxillary second molars with fused roots: a micro-CT study. Int Endod J. 2017;50(12):1192-1200. doi:10.1111/iej.12752.Nagendrababu V, Chong BS, McCabe P, Shah PK, Priya E, Jayaraman J, et al. PRICE 2020 guidelines for reporting case reports in Endodontics: a consensus-based development. Int Endod J . 2020;53(5):619-626.doi: 10.1111/iej.13285.Al-Fouzan KS. C-shaped root canals in mandibular second molars in a Saudi Arabian population. Int Endod J. 2002;5:499–504. doi:10.1046/j.1365-2591.2002.00512.x.Versiani MA, Alves FR, Andrade-Junior CV, Marceliano-Alves MF, Provenzano JC, Rôças IN, et al . Micro-CT evaluation of the efficacy of hard-tissue removal from the root canal and isthmus area by positive and negative pressure irrigation systems. Int Endod J.  2016;49(11):1079-1087. doi:10.1111/iej.12559.Ahmed HMA, Dummer PMH. A new system for classifying tooth, root and canal anomalies. Int Endod J.  2018;51(4):389-404.doi:10.1111/iej.12867.Wu MK, Wesselink PR, Walton RE. Apical terminus location of root canal treatment procedures. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.  2000;89(1):99-103. doi:10.1016/S1079-2104(00)80023-2.Han X, Yang H, Li G, Yang L, Tian C, Wang Y. A study of the distobuccal root canal orifice of the maxillary second molars in Chinese individuals evaluated by cone-beam computed tomography. J Appl Oral Sci.2012;20(5):563-567.doi:10.1590/S1678-77572012000500012.Cotti E, Campisi G. Advanced radiographic techniques for the detection of lesions in bone. Endod Topics. 2004;7(1):52-72. doi:10.1111/j.1601-1546.2004.00064.x.Patel S, Brown J, Pimentel T, Kelly RD, Abella F, Durack C. Cone beam computed tomography in Endodontics - a review of the literature.Int Endod J.  2019;52(1):1138-1152. doi:10.1111/j.1601-1546.2004.00064.x.

Skull Base Osteomyelitis with Extensive Bony Erosion Complicated by Venous Sinus Thrombosis

Introduced and invasive species make excellent natural experiments for investigating rapid evolution. Here, we describe the effects of genetic drift and rapid genetic adaptation in pink salmon (Oncorhynchus gorbuscha) that were accidentally introduced to the Great Lakes via a single introduction event 31-generations ago. Using whole-genome resequencing for 134 fish spanning five sample groups across the native and introduced range, we estimate that the progenitor population’s effective population size was 146,886 at the time of introduction, whereas the founding population’s effective population size was just 72—a 2040-fold decrease. As expected with a severe bottleneck, we show reductions in genome-wide measures of genetic diversity, specifically a 37.7% reduction in the number of SNPs and an 8.2% reduction in observed heterozygosity. Despite this decline in genetic diversity, we provide evidence for putative selection at 47 loci across multiple chromosomes in the introduced populations, including missense variants in genes associated with circadian rhythm, immunological response, and maturation, which match expected or known phenotypic changes in the Great Lakes. For one of these genes, we use a species-specific agent-based model to rule out genetic drift and conclude that a strong response to selection occurred in a period gene (per2) that plays a predominant role in determining an organism’s daily clock, matching large day length differences experienced by introduced salmon during important phenological periods. Together, these results inform how populations might evolve rapidly to new environments, even with a small pool of standing genetic variation.

A case report and clinical implications of medication-related osteonecrosis of the jaw resulting in sepsis in a patient with rheumatoid arthritis

Carbon dots (CDs) are an emerging class of nanomaterials with intriguing photophysical properties. Recently, achieving room-temperature phosphores-cence (RTP) for CDs have attracted considerable attention for biomedical and information applications. However, the CDs based RTP materials generally require the use of polymeric and inorganic matrix to provide the rigid environments, which remains a great challenge to obtain matrix-free CDs with RTP. Herein, a novel supramolecular strategy based on strong interparticle interactions has been developed to attain this objective, by covalent decoration of ureido-pyrimidinone (UPy, a multiple hydrogen bonding unit) on the surface of CDs. Structural characterizations validated the core-shell structure of the as-prepared CDs (EDTA-CDs) and demonstrated the successful attachment of UPy via post-modification (UPy-CDs). The presence of UPy recognition units render the strong hydrogen bonding between UPy-CDs, which stabilizes the triplet state via rigidifying effect. As a result, UPy-CDs exhibit matrix-free efficient RTP (λem = 534 nm) with high brightness and long lifetime (33.6 ms) in the solid state. Owing to the dual-emission character, we further explored the application potential of UPy-CDs in information encryption and anti-counterfeiting. Overall, this work provides a new and facile strategy for achieving matrix-free phosphorescent CDs with elegant incorporation of supramolecular chemistry.

A proper allergy work-up, based on the gold standard drug provocation test (DPT), usually rules out suspected drug hypersensitivity in children. These tests are generally open, given their high efficiency compared to double-blind placebo-controlled DPTs. Although their negative predictive value is excellent, no studies have calculated their positive predictive value, highly dependent on the prevalence of the disease. Most studies have found a rate of less than 5% to 10% of true beta-lactam hypersensitivity in children. Given this low prevalence (pre-test probability), a few false positive results can significantly reduce the estimated positive predictive value. False positives may arise from the nocebo effect during the test, including nocebo by proxy, or from observer bias, which depends on professional expertise and organizational circumstances. Some studies have found a high rate of tolerance on a second DPT in children who failed the first, but these results may be affected by the interval between the two tests, of a year or more in most cases, reflecting a loss of hypersensitivity over time. Taking into account the low rate of positive DPTs, with commonly mild reactions, we suggest confirming non-severe positive DPTs with a second provocation performed soon after the first, especially in the case of beta-lactam antibiotics, in order to improve the diagnostic accuracy, de-label more patients, and achieve a better estimation of true drug hypersensitivity prevalence.

Introduction: This study aimed to evaluate the cyclic and torsional fatigue resistance of a new nickel-titanium (Flat File 25.04) instrument on continuous and reciprocating motion. Methods: Sixty instruments of the ProDesign Logic2 25.03 and 25.05 (Easy Equipamentos Odontológicos, Belo Horizonte, Brazil), and MK Flat File 25.04 (n=20) (MK Life, Porto Alegre, Brazil) were used. For the cyclic fatigue test, an artificial stainless steel simulated canal with an angle of 60° and a radius of curvature of 5mm located 5mm from its tip was used. Torque and angle of rotation at failure of instruments on torsional fatigue test was based on the ISO 3630-1 protocol, in which the 3mm tip of each instrument was fixed and connected to an electric motor and a load cell. The fractured surface of each fragment was examined by scanning electron microscopy. Data were analyzed using 1-way analysis of variance and Tukey’s test with a significance level of 5%. Results: Flat File 25.04 had lower cyclic fatigue in both kinematics than the Logic instruments (P < .05). Reciprocating motion improved the cyclic fatigue of the tested instruments (P < .05). Flat File 25.04 had similar torque to Logic2 25.05 (P < .05), and both were superior to Logic2 25.03 (P < .05). The angular deflection values were different for the three tested instruments (P < .05), in the decreasing order: Logic2 25.03, 25.05, and Flat File 25.04. Conclusion: Flat File presented acceptable resistance to cyclic and torsional fatigue resistance. Reciprocating motion improved the cyclic fatigue resistance of the instruments and can be considered when using programmable motors.

In this paper, we study a time-fractional initial-boundary value problem of Kirchhoff type involving memory term for non-homogeneous materials ( P α ). As a consequence of energy argument, we derive L ∞ ( 0 , T ; H 0 1 ( Ω ) ) bound as well as L 2 ( 0 , T ; H 2 ( Ω ) ) bound on the solution of the problem ( P α ) by defining two new discrete Laplacian operators. Using these a priori bounds, existence and uniqueness of the weak solution to the considered problem is established. Further, we study semi discrete formulation of the problem ( P α ) by discretizing the space domain using a conforming FEM and keeping the time variable continuous. The semi discrete error analysis is carried out by modifying the standard Ritz-Volterra projection operator in such a way that it reduces the complexities arising from the Kichhoff type nonlinearity. Finally, we develop a new linearized L1 Galerkin FEM to obtain numerical solution of the problem ( P α ) with a convergence rate of O ( h + k 2 − α ) , where α (0 1) is the fractional derivative exponent, h and k are the discretization parameters in the space and time directions respectively. This convergence rate is improved to second order in the time direction by proposing a novel linearized L2-1 σ Galerkin FEM. We conduct a numerical experiment to validate our theoretical claims.

Reliable estimates of population size and demographic rates are central to assessing the status of threatened species. However, obtaining individual-based demographic rates requires long-term data, which is often costly and difficult to collect. Photographic data offer an inexpensive, non-invasive method for individual-based monitoring of species with unique markings, and could therefore increase available demographic data for many species. However, selecting suitable images and identifying individuals from photographic catalogues is prohibitively time-consuming. Automated identification software can significantly speed up this process. Nevertheless, automated methods for selecting suitable images are lacking, as are studies comparing the performance of the most prominent identification software packages. In this study, we develop a framework that automatically selects images suitable for individual identification, and compare the performance of three commonly used identification software packages; Hotspotter, I3S-Pattern, and WildID. As a case study, we consider the African wild dog Lycaon pictus, a species whose conservation is limited by a lack of cost-effective large-scale monitoring. To evaluate intra-specific variation in the performance of software packages, we compare identification accuracy between two populations (in Kenya and Zimbabwe) that have markedly different coat colouration patterns. The process of selecting suitable images was automated using Convolutional Neural Nets that crop individuals from images, filter out unsuitable images, separate left and right flanks, and remove image backgrounds. Hotspotter had the highest image-matching accuracy for both populations. However, the accuracy was significantly lower for the Kenyan population (62%), compared to the Zimbabwean population (88%). Our automated image pre-processing has immediate application for expanding monitoring based on image-matching. However, the difference in accuracy between populations highlights that population-specific detection rates are likely and may influence certainty in derived statistics. For species such as the African wild dog, where monitoring is both challenging and expensive, automated individual recognition could greatly expand and expedite conservation efforts.

DYT1 dystonia is a form of generalized dystonia associated with abnormalities in striatal dopamine release in mouse models and likely in humans. In the present study, we examined the possibility that ultrastructural changes in the morphology of nigrostriatal dopamine terminals could contribute to this neurochemical imbalance using a Serial-Block Face/Scanning Electron Microscope (SBF/SEM) and three-dimensional reconstruction approach to analyze striatal tyrosine hydroxylase-immunoreactive (TH-IR) terminals and their synapses in a DYT1(ΔE) Knockin (DYT1-KI) mouse model of DYT1 dystonia. Furthermore, to study possible changes in vesicle packaging capacity of dopamine, we used transmission electron microscopy to assess possible changes in the size of synaptic vesicles in striatal dopamine terminals between wild type (WT) and the DYT1-KI mice. Quantitative analysis of 80 fully reconstructed TH-IR terminals in the WT and DYT1-KI mice indicate: 1) No significant difference in the volume of TH-IR terminals between WT and DYT1-KI mice, 2) No major change in the proportion of axo-spinous vs axo-dendritic synapses formed by TH-IR terminals between the two groups, 3) No significant change in the post-synaptic density (PSD) area of axo-dendritic synapses, while the PSDs of axo-spinous synapses were significantly smaller in DYT1-KI mice, 4) No significant difference in the mean volume of mitochondria between WT mice and 5) No significant difference in the surface area of synaptic vesicles between the two groups. Altogether, these findings suggest that abnormal morphometric changes of nigrostriatal dopamine terminals and their post-synaptic targets are unlikely to be a major source of reduced striatal dopamine release in DYT1 dystonia.

Pelvic dimensions and hypotheses on duration of active second stage of labourTilde Broach OstborgStavanger University HospitalTM EggeboTrondheium University HospitalWe would like to thank Jan Novák and Petr Sedlak for their interest and comments to our manuscript. We found that increasing BMI was associated with shorter estimated median duration of the active second stage of labour.1We could not find any obvious causal mechanism for our findings; but suggested some possible explanations. The shorter active second stage may be related to increased abdominal pressure with increasing BMI, or perhaps increased strength when pushing.2, 3 Increased infiltration of fat in the muscular pelvic floor may decrease its strength and resistance.4 The presence of fat in the birth canal of obese women may delay the urge to bear down, thereby postponing active pushing until the head is lower in the maternal pelvis.Novak et al. measured the bi-ilac and bi-cristal diameters of the greater pelvis and found a broader pelvis in individuals with a history of obesity from adolescence.5 We supposed that there would be an association between the size of the greater pelvis and the size of the birth canal. We agree to the limitations commented by Novák and Sedlak. However, our proposed causal mechanisms are merely hypotheses, and cannot be accepted nor rejected based on current knowledge.1. Ostborg TB, Sande RK, Kessler J, Tappert C, von Brandis P, Eggebo TM. Put your weight behind it-Effect of body mass index on the active second stage of labour: A retrospective cohort study. BJOG. 2022;129:2166-2174.2. Lambert DM, Marceau S, Forse RA. Intra-abdominal pressure in the morbidly obese. Obes Surg. 2005;15:1225-1232.3. Tomlinson DJ, Erskine RM, Morse CI, Winwood K, Onambele-Pearson G. The impact of obesity on skeletal muscle strength and structure through adolescence to old age. Biogerontology. 2016;17:467-483.4. Pomian A, Lisik W, Kosieradzki M, Barcz E. Obesity and Pelvic Floor Disorders: A Review of the Literature. Med Sci Monit. 2016;22:1880-1886.5. Novak JM, Bruzek J, Zamrazilova H, Vankova M, Hill M, Sedlak P. The relationship between adolescent obesity and pelvis dimensions in adulthood: a retrospective longitudinal study. PeerJ. 2020;8:e8951.

Objective: To investigate programming effects of maternal testosterone on offspring birth anthropometrics. Design: Population-based prospective cohort study. Setting: University Hospital. Population: 1,486 mother-child dyads from Odense Child Cohort. Methods: Maternal blood samples were collected at gestational week 27-30 and free testosterone (FT) levels were calculated using the Vermeulen equation from total testosterone (TT) analyzed by mass spectrometry and sex hormone binding globulin (SHBG). Associations between FT or TT levels and birth anthropometrics were analyzed with multiple linear regression models according to offspring sex with adjustment for maternal age, parity, smoking and educational level. Analyses were repeated with polycystic ovary syndrome (PCOS) as exposure for offspring birth anthropometrics. Main outcome measures: Offspring birth weight (BW), birth length, abdominal- and head circumferences. Results: Maternal mean (SD) age was 30.2 (4.5) years and pre-pregnancy body mass index (BMI) was 23.5 (5.3) kg/m2. In boys (n=787), higher FT was associated with lower BW (adjusted doubling constant=-65.53, p=0.010), shorter birth length (adjusted doubling constant=-0.43, p<0.001), and lower abdominal circumference (adjusted doubling constant=-0.39, p<0.001); Higher TT was associated with lower abdominal circumference (adjusted doubling constant=-0.25, p=0.028). In girls, no associations were found between maternal FT or TT and offspring anthropometrics. Conclusions: Higher maternal free testosterone exposure was linked to reduced birth weight, length and abdominal circumference in boys, whereas girls were not susceptible to maternal testosterone exposure.

A document by Kobe Haenen. Click on the document to view its contents.

During thyroid surgery fast and reliable intra-operative pathological feedback has the potential to avoid a two-stage procedure and significantly reduce health care costs in patients undergoing a diagnostic hemithyroidectomy (HT). We explored higher harmonic generation (HHG) microscopy, which combines second harmonic generation (SHG), third harmonic generation (THG), and multiphoton excited autofluorescence (MPEF) for this purpose. With a compact, portable HHG microscope, images of freshly excised healthy tissue, benign nodules (follicular adenoma) and malignant tissue (papillary carcinoma, follicular carcinoma and spindle cell carcinoma) were recorded. The images were generated on unprocessed tissue within minutes and show relevant morphological thyroid structures in good accordance with the histology images. The thyroid follicle architecture, cells, cell nuclei (THG), collagen organization (SHG) and the distribution of thyroglobulin and/or thyroid hormones T3 or T4 (MPEF) could be visualized. We conclude that SHG/THG/MPEF imaging is a promising tool for clinical intraoperative assessment of thyroid tissue.

The effect of the simultaneous presence of fluorine (0.15-1.2 mg L -1), bicarbonates (83.6-596 mg L -1), and synthesized goethite (0.3 mg L -1) at typical concentrations often found in natural groundwater samples was evaluated on the degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) at pH 6.9 under simulated sunlight irradiation (300 W m -2) and H 2O 2 concentrations of 10 mg L -1. 2,4-D removal was strongly enhanced by the presence of fluoride. F - could modify the surface of iron (hydr)oxide leading to the formation of surficial Fe-F bonds benefiting the formation of free •OH radicals, producing upward band bending, reducing the electron-hole recombination, and enhancing the electron transfer to H 2O 2. On the other hand, bicarbonate may react with •OH radicals generating CO 3 -• species which could be able to participate in pollutant oxidation as well while solar light-induced H 2O 2 photolysis also played an important role in removing 2,4-D. These findings suggest that “natural” tuning of iron (hydr)oxides by fluoride could take place in natural groundwater generating “natural” photocatalysts with a high activity which could participate, by adding H 2O 2, in the enhancing of sunlight photoinduced natural abiotic processes to pollutants abatement.

Fractionation of proteoforms is currently the most challenging topic in the field of protein purification. The need for considering the existence of proteoforms into experimental approaches is not only important in Life Science research in general but especially in the manufacturing of therapeutic proteins (TPs) like recombinant therapeutic antibodies (mAbs). Some of the proteoforms of TPs have significantly decreased actions or even cause side effects. The identification and removal of proteoforms differing from the main species, having the desired action, is challenging because the difference in the composition of atoms often is very small and their concentration in comparison to the main proteoform can be small. In this study we demonstrate that sample displacement batch chromatography (SDBC) is an easy to handle, economic and efficient method for fractionating proteoforms. As a model sample a commercial ovalbumin fraction was used, containing many ovalbumin proteoforms. The most promising parameters for the SDBC were determined by a screening approach and applied for a 10-segment fractionation of the ovalbumin with cation exchange chromatography resin. Mass spectrometry of intact proteoforms was used for characterizing the SDBC fractionation process. By SDBC a significant separation of different proteoforms was obtained.

Aims: Therapeutic non-compliance remains the main difficulty for people with psychotic disorders, standing around 50% in people with schizophrenia. Lack of treatment adherence, either partial or total, to medication has economic and clinical consequences. E-health technologies may be a promising therapeutic tool to improve adherence, with the subsequent reduction in clinical and economic burden. Incorporating Information and Communication Technologies (ICT) has improved the information patients receive and the relationship between health professionals and patients. Our aims were to know the preferences on how technologies in mental health treatment should be for use in clinical practice, and to learn about the opinion and preferences on the use of technologies in mental health treatment from the perspectives of patients with FEP, their relatives, and mental health professionals. Methods: A cross-sectional quantitative study was carried out by experts in psychosis and technologies. 41 patients with a diagnosis of first-episode psychosis (FEP), 18 relatives and 49 mental health professionals were included in the study. Results: An app directed to people with psychosis would be well received by users if it contains psychoeducational material, offers reminders for scheduled visits and treatment and allows online consultations. Conclusions: Co-creating an app with users, their families and mental health professionals allows incorporating their preferences to increase its use, improve outpatient care and creating an app that is viable in clinical practice.

Habitat loss and habitat fragmentation usually occur together, at the same time and place. However, while there is consensus that habitat loss is the preeminent threat to biodiversity, the effects of fragmentation are contentious. Some argue that habitat fragmentation is not bad for biodiversity, and even that it is good. Generally, the studies that find no harm or positive outcomes of fragmentation invariably assume that it is independent of habitat loss. However, dissociating the effects of habitat fragmentation from habitat loss is questionable because of the two are essentially coupled. Accordingly, we evaluated how forest area and fragmentation (via edge effects) influenced dung beetles per se, and through their effects on the abundance of mammals, using structural equation modeling (SEM). Dung beetles are very sensitive to forest habitat loss and fragmentation, and to changes in the abundance of mammals on which they depend for dung. Our study area was in the Tana River, Kenya, where forest fragments are depauperate of mammals except for two endemic species of monkeys. We mapped 12 forests, counted the resident monkeys, and sampled 113,959 beetles from 288 plots. Most of the 87 species of beetles were small, affirming the endemic monkeys as the main source of dung. After implementing a fully latent Structural Regression SEM, the optimal model explained a significant 26% of the variance in abundance, and 89% of diversity. The main drivers of beetle abundance were positive, direct, effects of forest area and number of monkeys, and negative edge effects. The main drivers of diversity were the direct effects of the beetle abundance, indirect effects of forest area and abundance of mammals, and indirect negative edge effects. Thus forest area, fragmentation (via edge effects) and the number of monkeys jointly influenced the abundance and diversity of the beetles directly and indirectly.