Abstract Person-specific three-dimensional computational modelling plays a vital role in modern day research of cochlear implants to assist in understanding the neural interface of the cochlea and implanted electrode array. Further improvements are made to these models as more parameters are included. Landmark assessment provides information and is frequently used to register co-ordinates for model generation as it captures small variations. Objectives: The objective of this study is to identify and define landmarks to describe the internal auditory canal adequately for inclusion in the three-dimensional computational models of the cochlea and its surrounding structures. Participants: Retrospectively collected computer tomography scans of live human cochleae were collected. Descriptive and comparative statistics were used to describe the data obtained from the scans. Results: The mean anterior-posterior (AP) diameter at the base on the basal turn, the AP diameter at the midpoint of the IAC, the anterior and posterior length of the internal acoustic canal were measured. 57.14% of the internal acoustic canals observed presented with a cylindrical, 40.48% was funnel-shaped and 2.38 % was bud-shaped. A statistically significant difference was found between the diameters of the male and female internal acoustic meatii. Conclusion: This paper serves as a reference providing a landmark set for the description of the internal acoustic canal for inclusion in three-dimensional computational reconstruction of the cochlea and surrounding structures.

Background and Purpose: The G protein-coupled receptor kinase 2 (GRK2) is an important regulator of inflammation and pathological macrophage phenotype in a variety of diseases. We hypothesize that Gβγ-GRK2 signaling promotes early inflammatory response and chondrocyte loss in osteoarthritis (OA). Experimental Approach: Using the destabilization of the medial meniscus (DMM) model in 12-week-old male C57BL/6 mice, we determined the role of Gβγ-GRK2 signaling in synovitis, macrophage activation, and OA development. We achieved Gβγ-GRK2 inhibition at the time of DMM by administering the Gβγ inhibitor “gallein” and the GRK2 inhibitor “paroxetine” daily, starting from 2 days before DMM surgery, for a duration of 1 or 12 weeks. Synovial and cartilage structural changes were evaluated by histomorphometry. Molecular events and macrophage activation were examined using immunofluorescence staining, and chondrocyte apoptosis by TUNEL staining. We studied the direct role of Gβγ-GRK2 in synovitis and macrophage activation in vitro using SW982 and THP1 cells. Key Results: Continuous Gβγ-GRK2 inhibition initiated at the time of DMM attenuated OA development and decreased chondrocyte loss more effectively than delayed treatment. GRK2 expression and M1 macrophage phenotype were elevated in the inflamed synovium, while early gallein and paroxetine treatment for 1 and 12 weeks following DMM resulted in their reduction and upregulated M2 macrophage phenotype. In vitro experiments showed that Gβγ-GRK2 inhibition attenuated synoviocyte inflammation and M1 phenotype. Conclusion and Implications: We show that early Gβγ-GRK2 inhibition is of higher therapeutic efficacy in OA than delayed inhibition, as it prevents OA development by inhibiting the early inflammatory response.

Post-copulatory sexual selection is theorized to favor female traits that allow them to control sperm use and fertilization, leading to the prediction that female reproductive traits that influence sperm migration should differ between polyandrous and monogamous species. Here we exploit natural variation in the female mating strategies of closely related Peromyscus mice to compare female traits that influence sperm motility – the viscosity, pH, and calcium concentration ¬of fluids in the reproductive tract – between polyandrous and monogamous species. We find that the viscosity and pH, but not calcium concentration, of fluids collected from both the uterus and the oviduct significantly differ between species based on mating system. Our results demonstrate the existence of a viscosity gradient within the female reproductive tract that increases in monogamous species but decreases in polyandrous species. Both species have a more alkaline environment in the uterus than oviduct, but only in the polyandrous species did we observe a decrease in calcium in the distal end of the tract. These results suggest that fluid viscosity and pH in the female reproductive tracts of these mice may be influenced by post-copulatory sexual selection and provide a promising potential mechanism for female sperm control given their importance in modulating sperm behavior.

Background and Purpose: Mitochondrial dysfunction leads to degeneration of dopamine (DA) neurons. Previous studies have showed that mitochondrial NAD+-dependent acetylase Sirtuin 3 (SIRT3) is downregulated in aging-related neurodegenerative disorders. Here, we determined the effect of downregulation of SIRT3 on acetylation of mitochondrial complex II (succinate dehydrogenase) subunit A (SDHA) and explored whether SIRT3 activating agents would rescue complex II activity and improve mitochondrial bioenergetics in PD models. Experimental Approach: SD rats and differentiated MN9D cells were treated with rotenone (ROT) to establish animal and cellular PD models. SIRT3 activators including icariin (ICA) and honokiol (HNK) were employed to activate SIRT3 in the PD models. Protein acetylation was detected using western blot and immunoprecipitation. Activities of SIRT3 and mitochondrial Complex II, NAD/NADH ratio, mitochondrial respiration and ATP production were assessed in different models. Key Results: SIRT3 activity was suppressed in ROT-induced PD models. The downregulation of SIRT3 resulted in hyperacetylation of SDHA, leading to compromised activity of mitochondrial complex II and a decline in ATP production. Mechanistically, the suppression of SIRT3 activity was attributed to the decrease of NAD+/NADH ratio caused by the inhibition of mitochondrial complex I induced by ROT. Activation of SIRT3 by ICA and HNK improved complex II activity and elevated the production of ATP, resulting in protection against ROT-induced injuries to DA neurons. Conclusion and Implications: These findings reveal an unrecognized regulatory SIRT3-SDHA axis, and improving bioenergy deficiency through SIRT3 activation dependent rescue of mitochondrial complex II activity may provide an effective strategy for protecting neuronal degeneration.

Immediate skin rashes,flushing,urticaria pruritus,rhinorrhea,nausea,short retching,and/or vomiting,coughing, and vertigo are symptoms of mild hypersensitivity reactions.Recognizing the type of contrast reaction is crucial to treating it.Rapid recognition of the signs and symptoms of a contrast response allows radiology personnel to quickly determine the type of reaction, allowing for faster treatment and reversal.

We present the case of a 55-year old male patient who developed hyperkalemia after using Cotrimoxazole(TMP-SMX).He developed an elevated level of potassium from day-4 which kept on increasing until the drug was withheld on day-8.There was a marked increase in levels from 3.0(baseline) to 6.2 before the drug was withheld.

The anti-cancer activity of glycyrrhizin (licorice) against various types of breast cancer (BC) has been reported so far. However, a complete investigation for understanding the pathways that could be affected by this herbal compound as an anti-breast cancer agent has not been performed yet. This study tends to investigate the proteins and pathways involved in the anti-BC activity of glycyrrhizin. For this purpose, the target genes of glycyrrhizin were obtained from the ChEMBL database. The BC-associated genes for three kinds of BC were retrieved from DisGeNET. The target genes of glycyrrhizin and the BC-associated genes were compared, and the genes with disease specificity index (DSI > 0.6) were selected for further evaluation using in silico methods and bioinformatics tools. The protein-protein interaction (PPI) network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. The results revealed 80 common genes among the glycyrrhizin target genes and breast carcinoma-associated genes. Ten genes had a DSI greater than 0.6. The binding affinity of glycyrrhizin to these proteins and binding characteristics were assessed using molecular docking and binding free energy calculations (MM/GBSA). POLK, TBXAS1, and ADRA1A showed the highest binding affinity with -8.9, -9.3, and -9.6 kcal/mol, respectively. ErbB signaling pathway and PD-L1 expression and PD-1 checkpoint pathway in cancer are the potent pathways for the anti-BC activity of glycyrrhizin. By affecting the obtained targets and modulating the mentioned pathways, glycyrrhizin can influence and control BC efficiently.

In a patient with a history of hepatitis B virus-related hepatocellular carcinoma, a tumor initially diagnosed as hepatic hemangioma gradually increased in size over a 7-year period. Considering malignancy, surgery was performed. Histopathologically the tumor was diagnosed as combined hepatocellular-cholangiocarcinoma.

We consider a class of Schrödinger–Kirchhoff equations in $\mathbb{R}^{3} $ with a general nonlinearity $g$ and coercive sign-changing potential $V$ so that the Schrödinger operator -aΔ+V is indefinite. The nonlinearity considered here satisfies the Ambrosetti-Rabinowitz type condition g(t)t≥μG(t)>0 with μ>3. By Morse theory, we obtain the existence of nontrivial solutions for this problem.

Recently, an infinitesimal approach for finding reciprocal transformations has been proposed. The method uses the group analysis approach and consists of similar steps as for finding an equivalence group of transformations. The new method provides a systematic tool for finding classes of reciprocal transformations (group of reciprocal transformations). Similar to the classical group analysis this approach can be also applied for finding all reciprocal transformations (not only composing a group) of the equations under study. The present paper provides this algorithm. As an illustration, the method is applied to the two-dimensional stationary gas dynamics equations. Equivalence group, group of reciprocal transformations and completeness of all discrete reciprocal transformations are presented in the paper. The results are stated in form of a theorem.

Nutraceuticals are gaining importance owing to the increasing focus on overall health due to recent pandemic. Nutraceuticals include products which help in maintaining immunity and prevent diseases. It also includes products which support the optimal functioning of the human body. Poor nutrition plays an important role in non-communicable diseases and lifestyle-related disorders as well. Hence it has significant impact on overall public health. Various nutraceuticals have exhibited therapeutic potential and hence gained popularity. Nutraceuticals are mainly categorized into dietary supplements and functional foods. With multiple factors contributing to the growth of nutraceuticals industry in India, we are marching towards global leadership in nutraceuticals. Food Safety and Standards Authority of India is solely responsible for regulating the approval, promotions, and labeling standards for health supplements and nutraceuticals. As the understanding of these nutritional products is improving, the regulations are becoming more specific. There is a need to monitor the usage of such nutritional products regularly and stringently. Nutrivigilance and phytovigilance are relatively new concepts in our country; however, regulatory authorities need to proactively observe for the undesirable, unintended effects and issues related to substandard and counterfeit nutraceutical products. Healthcare professionals including pharmaceutical physicians and public health professionals can play an important role in safeguarding the population by advocating rational use of nutraceuticals, food supplements, and consumer health products.

In this study, we introduce the domains X(Aru), where the triangle matrix Aruis a general- ization of the Cesàro matrix and X denotes any of the classical spaces c0, c or ℓ∞ of null, convergent or bounded sequences. We also give the bases and determine the α-, β- and γ-duals of the spaces X(Aru). We characterize the classes (ℓ∞(Aru) : ℓ∞), (ℓ∞(Aru) : c), (c(Aru) : c), and (X : Y (Aru)) of infinite matrices, where Y denote any given sequence space. Furthermore, we also give a Steinhaus type theorem. As another result of this study, we investigate the ℓp-norm of the matrix Aruand as a result obtaining a generalized version of Hardy’s inequality and some inclusion relations. Moreover, we compute the norm of well-known operators on the matrix domain ℓp(Aru).

Background: Cystic fibrosis (CF) is an inherited autosomal recessive disorder that causes chronic airway disease. In addition to genetic factors, environmental factors may affects the clinical phenotype of CF. In our study, the presence of aeroallergen sensitivity in our patients with CF and its effects on clinical findings were evaluated. Materials and Methods: Demographic characteristics, clinical and laboratory findings, skin prick test (SPT) results, and Modified Shwachman-Kulczycki (MSK) scores of patients diagnosed with CF followed in the Pediatric Respiratory and Allergy Clinic of Dokuz Eylul University Faculty of Medicine were evaluated. Results: We evaluated 51 patients with CF with a median age of 10 (6-18) years. The mean MSK score of the patients was 72.54±11.50, and the mean predictive value of forced expiratory volume (FEV1) in the first second of 41 patients was 80.43±19.50. According to SPT, aeroallergen sensitivity was detected in 17 (33.3%). The frequency of bacterial colonization and bronchiectasis was higher, MSK scores were lower in AF-sensitive patients (p≤0.01). However, there was no similar difference in other allergen sensitivities. MSK scores and predictive FEV1 values of 25 (49%) patients with bacterial colonization were significantly lower than those without colonization (p=0.001, p=0.005, respectively). Conclusion: Aeroallergen sensitivity was detected in approximately 1/3 of CF patients. Although it has been emphasized in studies that environmental factors may have an impact on lung functions and clinical conditions in CF, the effect of allergens other than AF sensitivity may be less important compared to other environmental factors such as the presence of bacterial colonization. Keywords: Cystic fibrosis, atopy, children, asthma, Aspergillus fumigatus, Pseudomonas aeruginosa

Refractory/relapsed acute myeloid leukemia is an advanced hematological malignancy with a poor prognosis in pediatric. The therapeutic options are limited and has been slow development of therapies for this age group. A combination of Venetoclax and Azacitidine therapy in newly diagnosed elderly patients with acute myeloid leukemia and refractory/relapsed disease has achieved impressive results. Whether similar results can be attained in pediatric patients is unknown. We present a case of adolescent girl with acute myeloid leukemia secondary to myelodysplastic syndrome, who was deemed unfit to undergo conventional chemotherapy and, was treated instead with the Venetoclax and Azacitidine.

Reverse transcription recombinase polymerase amplification assays combined with the fluorescence detection platform (qRT-RPA) and lateral flow biosensor (LFB RT-RPA) were developed and validated for rapid detection of porcine EMCV. The primers and probes were designed based on the highly conserved region of 3D gene of porcine EMCV. The optimal reaction condition of qRT-RPA and LFB RT-RPA assay was at 42 °C for 20 min. The assays were highly specific to EMCV and no cross-reactions were observed with other 7 porcine viruses. With the 10-fold sieral diluted EMCV genomic RNA as template, the limit of detection of the qRT-RPA assay was 1.0×10 2 copies and the limit of detection of LFB RT-RPA was 1.0×10 1 copies. A total of 92 samples collected from EMCV inoculated mice (24), control mice (8) and pigs showing reproductive failures (60) were examined using developed RT-RPA and a described qRT-PCR, and the diagnostic agreement between qRT-RPA (23/92), LFB RT-RPA (25/92) and qRT-PCR (23/92) was 100% and 97.83, respectively. The performances of the developed RT-RPA assays were comparable to a qRT-PCR, while the RPA assays needed less time and easy to perform to obtain the positive results and LFB RT-RPA was higher sensitive than the qRT-PCR. The developed EMCV RT-RPA assays are rapid, reliable and easy to perform, which provide an attractive and promising tool for effective detection of EMCV in low-resource settings.

Abstract: Objective: To investigate the histopathologically, diagnostic measure and prognosis of Struma Ovarii (SO). Design and Setting:From Jan.2009 to Jan.2022, the general clinical data, results of laboratory examinations, surgical and histopathological test results of 11 patients, age 25-66 years, mean45.5 years old, with struma ovary in the department of Gynecoloy in The Affiliated Hospital of Jiangnan University, were analyzed retrospectively. Population or Sample：1 Struma Ovarii (SO) cases. Methods: Methods Clinical data of 11 Struma Ovarii (SO) cases were retrospectively studied, analyzed the histopathologically, diagnostic measure and prognosis of (SO). In this study, the procedure followed in line with our hospital customized ethical standards, and with the signing of informed consent in clinical research which obtained a informed consent from the patients. Results: The clinical manifestations of these patients were pelvic mass, bloating, breathing difficulty, peritoneal dropsy, pelvic mass and the CA125 levels may be elevated. Conclusions: Struma Ovarii is a highly specific ovarian teratoma, mostly benign. Struma Ovarii is rare in clinical because its no obvious clinical feature and characteristics preoperative and intraoperative diagnosis was difficult. Its preoperative misdiagnosis rate is high but the malignant transformation rate is very low, prognosis good for most of patients. Intraoperative frozen histopathological examination for early diagnosis can avoid unnecessary surgery to expand. Serial measurement of serum thyroglobulin is a sensitive and cost-effective follow-up tool. A period of at least 10 years is recommended.

Objective:To assess current quality of postnatal care in tertiary hospital in Lahore to identify areas for further improvement.Design:It was descriptive cross-sectional study which employed quantitative method to collect and analyze data.Setting:Lady Aitchison Hospital-a tertiary hospital in Lahore.Population:Ninety-six maternities admitted in wards of Lady Aitchison hospital during December 2021 to January 2022.Method:After IRB approval, consent was taken from mothers selected by random sampling and interviewed using Donabedian framework performa.Outcome Measures:Satisfaction with structure,process and outcome of delivery in postpartum mothers were assessed.Results:Among 96 mothers,56% were below 25 years of age,39% had secondary education,with more than one child(71%) and 57% visited for the first time.Majority of mothers,were given medicine timely(82%) and found attitude(85%) and information(83%) provided by healthcare workers helpful.Their subjective satisfaction rate with staff was 90%.However,there was lack of proper guidelines and facilities for examination,limited counselling of mothers regarding neonatal care and substandard interior of hospitals.Vital steps such as neonatal and maternal abdominopelvic,general and wound examination were left out in upto 30%. Information regarding danger signs of mothers and neonates was not given to 69% and information on family planning was given in only 28%.Contentment with infrastructure of hospital was subpar and it was suggested that sanitary conditions of washrooms and paraphernalia i.e.heaters and beds needed improvement.Conclusions:This study suggests that although patients were satisfied by services of healthcare workers,the infra-structure of hospital can be upgraded to provide better quality facilities in terms of air-conditioning,washrooms and well-designed areas for extensive examination of breast,pelvis,abdomen and neonates with introduction of WHO guidelines for postnatal care.

Immunohistochemical markers are associated with treatment outcome in adults with classical Hodgkin Lymphoma (cHL). Studies in children are scarce and inconsistent. We investigated in 67 children with cHL, whether the expression of CD15, CD30, PAX5, PD-1, PD-L1, CD68, CD163 and TARC is associated with the event-free survival (EFS) and the interim remission status. Low expression of PD-L1 was significantly associated with complete remission at interim PET-scan. There was no association between marker expression and EFS. Our data suggest a difference between pediatric and adult cHL. This underlies the importance of future research into specific molecular drivers in pediatric cHL.

Alkuraya-Kucinskas syndrome is a neurodevelopmental disorder due to mutation in KIAA1109 gene. We report a case of optic pathway tumor in a child with novel variant of KIAA1109. A plausible mechanism of gliomagenesis is considered based on influence of KIAA1109 on regulation of phosphatidyl inositol phosphorylation.

We report the case of a 10-year-old girl with an Askin Tumor who had a history of Acute Lymphoblastic Leukemia. Seven years after the diagnosis of ALL, her family detected a mass on her left chest wall. An ultrasound-guided tru-cut needle biopsy was performed and the diagnosis of a primitive neuroectodermal tumor of the chest wall (Askin Tumor) was finalized with histologic and genetic analysis. The risk of secondary cancer is three to 10 times higher in childhood cancer survivors than the general population. Patients who have several different types of cancers should be tested for hereditary cancer syndromes.

CASE REPORT

Conclusion The cervical pessary can extend the gestational week of short-cervix twin pregnancy without clinical symptoms, reduce the premature birth rate before 34 weeks of gestation, improve pregnancy outcome, reduce neonatal mortality, reduce necrotizing enterocolitis incidence, neonatal sepsis incidence, and improve neonatal outcome. For patients with a cervical length less than 38mm, a cervical pessary can be performed to extend the gestational week. For patients with a cervical length less than 25mm, a cervical pessary can effectively prolong the gestational age and improve the maternal and fetal outcomes. The cervical pessary is safe for patients with twin pregnancies. Suggest that twin-preganct-patients with CL<38mm should consider take cervical pessary in advance. In terms of long-term efficacy, there is no evidence of cervical support placement on the long-term maternal prognosis. In terms of economic benefits, cervical support is better than vaginal progesterone, but this conclusion still needs more research to prov

Aim: Vaccines have been mainly described to provide cardioprotective effects with rare reports showing rare association with myopericarditis. However, vaccines have not been well studied regarding its effects on heart rhythm disorders. Methods: we used vaccine adverse event reporting system (VAERS) between 1990-2021 to search for atrial fibrillation and other less prevalent arrhythmia. Disproportionality signal analysis was conducted by measuring reporting odds ratio (ROR) with 95% confidence interval (CI). Results: Over 1,300,000 adverse events were reported between 1990-2021. Among these events, atrial fibrillation was reported 2149 times in association with various vaccines. 90% of atrial fibrillation was associated with COVID-19 vaccines with ROR of 13.18 (CI 95%: 11.3 to 15.4) (P<0.0001). Interestingly, influenza vaccines, polyvalent polysaccharide pneumococcal (PPSV23) vaccine, pneumococcal 13-valent (PCV13) vaccine, zoster vaccine, and tetanus-containing vaccines were significantly associated with reduced atrial fibrillation. Finally, our analysis showed that COVID-19 vaccines were associated with much higher incidence of other cardiac arrhythmias compared with other vaccines. Conclusions: While vaccines have not been linked to heart rhythm disorders, the introduction of COVID-19 vaccines in 2020 showed significant association with atrial fibrillation. This study showed unprecedent detrimental effect of COVID-19 vaccines on atrial fibrillation and warrants the need to take that into consideration when prescribing COVID-19 vaccines.

Objective: To assess the impact of applying published fetal growth references or standards in the Chinese mainland population and to compare their ability to predict newborns small- for- gestational- age (SGA). Design: Retrospective observational study. Setting: A tertiary hospital in Shenzhen, a Chinese city with the most immigrants. Population: All pregnant women (n=106,455) who booked for prenatal care with ultrasound measurements for fetal biometry between 2012 and 2019. Methods: A fractional polynomial regression model was applied to construct Shenzhen fetal growth chart ranges for HC, BPD, AC, and FL. The differences between Shenzhen charts and published charts were quantified by calculating the Z-score. Main outcome measures: The impact of applying these published charts was quantified by calculating the proportions of fetuses with biometric measurements below the 3rd centile of these charts. The sensitivity and area under the receiver operating curves of published charts to predict neonatal SGA (birthweight <10th centile) were assessed. Results: Following selection, 169,980 scans of fetal biometry contributed by 41,032 pregnancies with reliable gestational age were analyzed. When using Hadlock references (<3rd), the proportions of small heads and short femurs were as high as 8.9% and 6.6% in late gestation, respectively. The Intergrowth-21st standards matched those of our observed curves better than other charts. When using AC<10th centile, all of these references were poor at predicting neonatal SGA. Conclusion: Applying Hadlock references could possibly misclassify a large proportion of fetuses as SGA. Conversely, applying the Intergrowth-21st standard appears to be a safe option in mainland China.