A document by Takeru Okouchi. Click on the document to view its contents.

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopamine neurons and aberrant deposits of alpha-synuclein (a-syn) in the brain. The symptomatic treatment is started after the onset of motor manifestations in a late stage of the disease. Preclinical studies show promising results of disease-modifying neuroprotective or even neurorestorative therapies with neurotrophic factors (NTFs). Three NTFs have entered phase I-II clinical trials with inconclusive outcomes. This is not surprising since the preclinical evidence is from acute early-stage disease models but the clinical trials included advanced PD patients. In order to conclude the value of NTF therapies, clinical studies should be performed in early-stage patients with prodromal symptoms, i.e. before motor manifestations. In this review, we summarize currently available diagnostic and prognostic biomarkers that could help identify at-risk patients benefiting from NTF therapies. Focus is on biochemical and imaging biomarkers, but also other modalities are discussed. Neuroimaging is the most important diagnostic tool today, but a-syn imaging is not yet viable. Modern techniques allow measuring various forms of a-syn in cerebrospinal fluid, blood, saliva and skin. Digital biomarkers and artificial intelligence offer new means for early diagnosis and longitudinal follow-up of degenerative brain diseases.

Gram staining can classify bacterial species into two large groups based on cell wall differences. Our study revealed that within the same Gram group (Gram-positive or Gram-negative), subtle cell wall variations can alter staining outcomes, with the peptidoglycan layer and lipid content significantly influencing this effect. Thus, bacteria within the same group can also be differentiated by their spectra. Using hyperspectral microscopy, we identified six species of intestinal bacteria with 98.1% accuracy. Our study also demonstrated that selecting the right spectral band and background calibration can enhance the model’s robustness and facilitate precise identification of varying sample batches. This method is suitable for analyzing bacterial community pathologies.

The domestic duck is classified as a specialist filter-feeder bird living in the water. These birds also use grazing and pecking as terrestrial feeding methods. The tongues of domestic ducks, similar to those of other Anseriformes, exhibit numerous types and shapes of mechanical papillae that serve a number of purposes when collecting food. Purpose: The current study attempts to describe the morphological characteristics of the tongue as well as the mechanical papillae’s development. In addition, the study aims to determine whether the papillae observed post-hatching exhibit similar morphology to those found in adult avian species, as well as to investigate the readiness of the tongue to fulfill its feeding function following hatching. The comprehensive examination of lingual mucosa is examined about the structural modifications necessary for this variety of feeding activities. Methods: In this study, the tongues of nine young and adult females were used. Results: The tongue had three distinct parts: the apex, which had a lingual nail on its ventral surface; the body, which exhibits numerous small and large conical papillae on its lateral sides and a lingual prominence in the caudal region; and the root, which is covered with numerous conical papillae of varying sizes. Conical, filiform, and hair-like mechanical papillae, the three types of food filtration apparatus, are present in both stages. The intra-oral transfer involves several structures, including the median groove, lingual combs, and the rostral border of the lingual prominence. The rostral border of the lingual prominence is characterized by distinct rows of conical papillae. The histological analysis demonstrated the presence of both keratinized and non-keratinized epithelium on different tongue regions. The lingual salivary glands in the rostral and caudal lingual salivary glands exhibit a pronounced periodic acid–Schiff (PAS)-positive reaction. Additionally, the yellow adipose tissue and sensory receptors, namely the Grandry and Herbst corpuscles, which collectively form the bill-tongue organ that monitors the movement of food. Research highlights, these results conclude the presence of microstructural species-specific alterations in specific tongue areas of domestic ducks’ lingual mucosa. These modifications are formed by the filtering mechanism and terrestrial feeding mechanisms such as grazing or pecking. Following hatching, the tongue of the domestic duck undergoes significant development, primarily in preparation for grazing activities. The anatomical and histological structure of the young tongue exhibited similarities to that of the adult domestic duck while also displaying certain variations that could potentially be attributed to the bird’s habitat and mode of feeding.

Title: Ruptured Giant Low-grade Mucocele of the Appendix and its Management: A Case ReportKey Clinical Message :Preoperative prompt imaging is crucial for a definitive diagnosis of appendiceal mucocele, and double-J stenting of the ipsilateral ureter in a large retroperitoneal cyst is recommended for easy identification and prevention of complications.Keywords :Appendix; appendiceal neoplasms; mucocele; pseudomyxoma peritonei; neoplasms; laparotomyIntroduction :Mucocele of the appendix is a well-described clinical condition of the appendix. It is a rare condition with an incidence of about 0.2-0.7 % of all appendectomies (1). The pathophysiology behind the appendiceal mucocele is an obstructive dilatation of the appendicular lumen by excess intra-luminal mucous secretions. Due to the presence of very vague presenting symptoms or even asymptomatic presentation, it is often diagnosed at an advanced clinical stage, or even misdiagnosed as acute appendicitis. It requires prompt imaging with preoperative planning and adequate surgical treatment, to avoid the rupture and spillage of the cystic content and to prevent the development of pseudomyxoma peritonei.Case Presentation :A 60-year-old hypertensive male came to the general surgery outpatient department with complaints of pain and distension in the abdomen for three years which was insidious in onset and progressive in nature. On examination, the abdomen was soft, non-tender, and distended with a vague lump felt in the right half of the abdomen (Fig. 1). There were no complaints of fever, weight loss, appetite loss, constipation, or vomiting. Laboratory investigations showed leucocytosis (13.20 x 103 /ul) with neutrophilia (9.09 x 103 /ul), and carcinoembryonic antigen (CEA) levels were elevated, 117.8 ng/ml.Abdominal ultrasonography showed a large intra-abdominal lobulated hypoechoic, likely cystic mass with internal echogenic areas on the right side. Abdominal contrast-enhanced computed tomography showed a large well defined multilobulated lesion of 17x13x24 cm in the retroperitoneum on the right side along with areas of whorled calcification in the superior aspect of the lesion. This gigantic cyst was pushing the retroperitoneal organs towards the left side (Fig. 2).Because of the large size of the mass, a decision to perform an exploratory laparotomy was made. A full-length midline incision was given and the mass was excised in toto with accidental spillage of content along with the part of the cecum (Fig. 3, 4). Intraoperatively, a large retroperitoneal cystic mass of 15.5 x 12 x 20 centimetres was found in connection with the body of the appendix. The cyst was extending superiorly to the dome of the diaphragm, medially to the lateral border of the inferior vena cava and inferiorly to the pelvis. Histopathology samples of the mass and cell cytology samples of the spillage liquid were sent. Microscopic examination of the cyst wall showed flattened to undulating columnar lining epithelium which was getting morphed into papillary infoldings, exhibiting mild nuclear pleomorphism, round to oval coarsely chromatic nuclei, inconspicuous nucleoli and abundant mucinous cytoplasm. The underlying lamina propria showed moderate chronic inflammatory infiltrate and desmoplasia. Histopathological diagnosis of “Low grade appendiceal mucinous neoplasm, pT4a” was made. The appendix base and part of the cecum were not involved in the tumour. The patient was discharged on a postoperative day-7 and has been followed up in the outpatient department with no reported complications for 6 months.Discussion :Mucocele was initially described by Rokitansky in 1842 (2). Most often, benign or malignant epithelial proliferation results in an obstructive dilatation of the appendix. Less frequently, inflammation or obstruction by a fecalith is the cause of mucocele formation (3). Some studies state a higher prevalence in females (1), while others confirm a higher prevalence in males (4). At our tertiary care referral centre, we have found that males above 50 years of age are more commonly affected by appendiceal mucocele.The clinical presentation of appendiceal mucocele is vague or sometimes asymptomatic. Due to this, patients often present late to the hospital. Usually delayed presentations of appendiceal mucocele are large abdominal lump, abdominal distension, acute appendicitis or acute abdomen or pseudomyxoma peritonei. Without proper in-time treatment, the whole abdomen may get involved due to perforation of the mucocele and dissemination of the mucin-producing epithelium in the peritoneal cavity, which may result in the development of pseudomyxoma peritonei. In our scenario, the patient presented to us with a large abdominal lump and abdominal distension. Ultrasound showed the classical onion skin sign suggestive of appendiceal mucocele (5). A contrast-enhanced computed tomography was performed for further characterization of the cystic mass and surgical planning. A correct diagnosis before surgery is of paramount importance for both planning the surgery and decreasing the risk of severe intraoperative and postoperative complications. The imaging techniques that can aid in the diagnosis of mucocele of the appendix are ultrasonography, computed tomography and colonoscopy.On computed tomography, a mucocele will typically manifest as a homogenous hypoattenuating material that has Hounsfield values similar to water filling the lumen of the appendix (3). A mucocele is highly likely if there is curvilinear calcification in the appendix’s wall (6). An elevated appendiceal mucocele can be seen during a colonoscopy and is called as “volcano sign” (7). A yellowish mucus discharge may be visible from this orifice (8). Histopathology is usually the standard investigation for establishing a definitive diagnosis of mucocele. Because of the risk of seeding neoplastic cells along the needle track or in the peritoneal cavity, which could produce pseudomyxoma peritonei, fine needle aspiration of an appendiceal mucocele is avoided (9).The treatment modality of choice for appendiceal mucocele is surgery. The basic guiding principle behind the surgery for an appendiceal mucocele is to retrieve the cyst intact without spillage, as a perforated appendiceal mucocele carries a higher risk of development of pseudomyxoma peritonei. The surgical method preferred for operating on the mucocele of the appendix is open surgery because of the higher risk of rupture of the mucocele laparoscopically (10). In open surgery, it is possible to do a complete in-situ manual examination of the intestines including palpation of the inflamed structure and also direct inspection of the most probable spots of mucinous tumours in the abdomen. Laparoscopic exploration does help in the confirmation of diagnosis. But now, because of the availability of high-resolution computed tomography with good diagnostic accuracy, a laparoscopic examination is seldom required.Our case showcases the importance of large size and location in the retroperitoneum of the appendiceal mucocele. Preoperative double-J stenting of the right ureter should be done in the retroperitoneal appendiceal mucocele for easy identification of the right ureter. Meticulous intraoperative handling and dissection are required to prevent the rupture of the cyst and its complications. An appendectomy, ileocecectomy or right hemicolectomy should be the only procedure performed during the initial surgery for a ruptured appendiceal mucinous lesion at non-specialized centres. Additionally, careful inspection of the abdominal cavity with documentation and biopsy of any suspicious peritoneal lesions should be done. To minimize tumour cell implantation, the surgical and abdomen wounds should be cleaned thoroughly by irrigation (11).Depending on the final detected pathology, a patient with gross peritoneal dissemination of mucin should thereafter be transferred to a specialized centre. A consensus classification developed by the Peritoneal Surface Oncology Group International has been instrumental in clearing up the ambiguity around diagnostic terminology (12).Our case was reported as “T4a low-grade mucinous neoplasm”, which should be managed with follow-up contrast-enhanced computed tomography or diagnostic laparoscopy at 6 to 12 months to look for recurrence or development of the tumour. Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy can then be offered if evidence of disease is detected.Conclusion :Appendiceal mucocele, albeit a rare disease, should always be kept as a differential diagnosis when the presenting symptoms are like acute appendicitis. Clinicians should be aware that the underlying pathology behind a mucocele of the appendix can range from a mere retention cyst to malignant tumours. To correctly diagnose a mucocele pre-operatively, contrast-enhanced computed tomography abdomen should be used extensively. The importance of contrast-enhanced computed tomography and other imaging modalities increases in large-size cysts. For larger cysts located in the retroperitoneum, preoperative double-J stenting of the right ureter is recommended for easy identification. Meticulous dissection to prevent spillage and to avoid the development of pseudomyxoma peritonei is a must.Author Contributions :Hritvik Jain : Conceptualization; writing – original draft; writing – review & editing. Dheerain Gupta : Conceptualization; writing – original draft, writing – review & editing. Jyoti Jain : Writing – original draft, writing – review & editing. Mahendra Lodha : Methodology; project administration; supervision; writing – review & editing. Binit Sureka : Writing – original draft. Prakriti Pokhrel : Writing – original draft.References :(1). Singh MP.(2020) A general overview of mucocele of appendix.9(12), 5867-5871.(2). B.B., S.K., Jasuja P.(2019) Appendiceal mucocele-A rare case report.58, 21-25.(3). Demetrashvili Z, Chkhaidze M, Khutsishvili K et al.(2012) Mucocele of the Appendix: Case Report and Review of Literature.97(3), 266-269.(4). Saad EA, Elsamani EY, AbdElrahim WE et al.(2018) Surgical treatment of mucocele of the appendix.2018(6), rjy102.(5). Caspi B, Cassif E, Auslender R et al.(2004) The onion skin sign: A specific sonographic marker of appendiceal mucocele.23(1), 117-121.(6). Tirumani SH, Fraser-Hill M, Auer R et al.(2013) Mucinous neoplasms of the appendix: A current comprehensive clinicopathologic and imaging review.13(1), 14-25.(7). Mastoraki A, Sakorafas G, Vassiliu P et al.(2016) Mucocele of the Appendix: Dilemmas in Differential Diagnosis and Therapeutic Management.7(1), 86-90.(8). Pickhardt PJ, Levy AD, Rohrmann CA et al.(2003) Primary neoplasms of the appendix: Radiologic spectrum of disease with pathologic correlation.23(3), 645-662.(9). da Fonseca LM, Lacerda-Filho A, da Silva RG.(2010) Pseudomyxoma peritonei syndrome 12 months after an intact resection of malignant mucocele of the appendix: A case report.65(8), 817-818.(10). Zuzarte JC, Liu YC, Cohen AM.(1996) Fine needle aspiration cytology of appendiceal mucinous cystadenoma: A case report.40(2), 327-330.(11). Barrios P, Losa F, Gonzalez-Moreno S et al.(2016) Recommendations in the management of epithelial appendiceal neoplasms and peritoneal dissemination from mucinous tumours (pseudomyxoma peritonei).18(5), 437-448.(12). Govaerts K, Lurvink RJ, De Hingh IHJT et al.(2021) Appendiceal tumours and pseudomyxoma peritonei: Literature review with PSOGI/EURACAN clinical practice guidelines for diagnosis and treatment.47(1), 11-35.Figure Legends :Figure 1: Preoperative image of the patient’s abdomen showing fullness in left hypochondrium and left lumbar region.Figure 2: CECT abdomen figure showing the axial (left side) and coronal (right side) view. The white dashed arrow is showing the displaced colon and the black dashed arrow is pointing towards the displaced right kidney hence confirming it to be predominantly retroperitoneal in location.Figure 3: Intraoperative image showing an in-situ cystic mass occupying the entire retroperitoneum.Figure 4: Postoperative image showing an excised specimen with mucin.

IntroductionStent thrombosis (ST) is a complication of percutaneous coronary intervention (PCI) with catastrophic clinical consequences and an incidence rate of 3% - 20% . Stent underexpansion and malapposition are the major causes of this complication that can be well-diagnosed and prevented by intracoronary imaging like intravascular ultrasound (IVUS) and optical coherence tomography (OCT) .This report presents a 60-year-old gentleman with a history of recent PCI on RCA (due to inferior NSTEMI). RCA stent thrombosis was diagnosed during staged PCI for LCX-OM which was successfully managed under the guidance of IVUS.

Natural plant populations often exhibit marked differences in gene expression patterns that can reflect heterogeneity in selective pressures. Analyzing gene expression as a quantitative trait provides a unique opportunity to evaluate the underlying genomic basis of a plethora of traits and their interactions in driving adaptive evolution. We investigated patterns and processes driving expression differentiation under conditions mimicking future climates by combining common garden experiments with transcriptome-wide datasets obtained from hybrid populations of Pinus strobiformis and P. flexilis. We found strong signals of genotype-environment interactions (GEI) at the individual transcript and the co-expression module levels suggesting a marked influence of drought related variables on adaptive evolution. Overall, survival was positively associated with P. flexilis ancestry, but it exhibited an environment-specific pattern. Co-expression modules exhibiting strong associations with survival and genomic ancestry were representative of similar functional categories across both gardens. Using network topology measures, putatively adaptive garden-specific expression traits were pleiotropic and belonged to modules exhibiting high population differentiation yet low preservation across gardens. Overall, our study suggests the presence of substantial genetic variation underlying univariate and multivariate traits in novel climates that may enable populations of long-lived forest trees to respond to rapid shifts in climatic conditions in early seedling stages when mortality tends to be the highest. Our finding of pleiotropic trait architectures underlying adaptive traits, however, implies rapid adaptive responses to changing selection pressures depend on whether trait covariances align with the direction of change in selection pressures.

Monte Carlo simulations have long been a widely used method in the industry for control system validation. They provide an accurate probability measure for sufficiently frequent phenomena, but are often time-consuming and may fail to detect very rare events. Conversely, deterministic techniques such as µ or IQC-based analysis allow fast calculation of worst-case stability margins and performance levels, but in the absence of a probabilistic framework, a control system may be invalidated on the basis of extremely rare events. Probabilistic µ-analysis has therefore been studied since the 1990s to bridge this analysis gap by focusing on rare but nonetheless possible situations that may threaten system integrity. The solution adopted in this paper implements a branch-and-bound algorithm to explore the whole uncertainty domain by dividing it into smaller and smaller subsets. At each step, sufficient conditions involving µ upper bound computations are used to check whether a given requirement – related to the delay margin in the present case – is satisfied or violated on the whole considered subset. Guaranteed bounds on the exact probability of delay margin satisfaction or violation are then obtained, based on the probability distributions of the uncertain parameters. The difficulty here arises from the exponential term classically used to represent a delay, which must be replaced by a rational expression to fit into the Linear Fractional Representation (LFR) framework imposed by µ-analysis. Two different approaches are proposed and compared in this paper. First, an equivalent representation using a rational function of degree 2 with the same gain and phase as the real delay, which results into an LFR with frequency-dependent uncertainty bounds. Then, a Padé approximation, whose order should be chosen carefully to handle the trade-off between conservatism and complexity. A constructive way to derive minimal LFR from Padé approximations of any order is also provided as an additional contribution. The whole method is first assessed on a simple satellite benchmark, and its applicability to realistic problems involving a larger number of states and uncertainties is then demonstrated.

Abstract Background: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a rare clinical-radiological being defined by the magnetic resonance imaging (MRI) finding of a reversible lesion in the corpus callosum. The most significant neurological symptoms are disturbance of consciousness and abnormal and delirious behavior.Case presentation: A seven-year-old male patient with a history of fever and cough was admitted to our hospital due to sudden-onset bilateral blindness. His physical examination showed confusion, fever, and delirious behavior with no focal neurological and meningeal irritation signs. The electroencephalogram showed diffuse slowing in favor of mild encephalopathy. Magnetic resonance imaging of the brain showed a signal alteration in the splenium of the corpus callosum and Magnetic Resonance Angiography (MRA) was normal. This finding was suggestive of a reversible cytotoxic lesion. Empiric antiviral treatment was initiated and the symptoms improved completely.Conclusion: Sudden blindness was reported as an initial symptom of MERS in a few children. Until now, there is no evidence of effective treatment methods. Nevertheless, MERS diagnosis provides pediatricians with beneficial prognostic information in order to convince patients and their families about the good outcome of this disease.Keywords: Reversible encephalopathy, Bilateral blindness, Corpus callosumIntroductionTada et al. first determined the concept of mild encephalopathy/encephalitis with a reversible splenial lesion (MERS) as an uncommon clinical-radiological syndrome in 2004[1, 2] which is mostly reported in East Asian populations [3]. It usually develops in children below sixteen-years-old and only occasionally in adults [4]. Infections are considered as the main trigger of the disease; the major pathogens associated with MERS are viruses, such as influenza virus (A and B) [3]. Non-infectious conditions related to reversible splenial lesions are seizures, antiepileptic drug withdrawal, metabolic disturbances, and renal or hepatic dysfunction [5]. To date, a common pathophysiological mechanism explaining selective splenial involvement has not been found. However, there are several hypotheses on MERS pathogenesis, including intramyelinic edema, hyponatremia, axonal damage, and oxidative stress [6]. MERS is typically characterized by a prodromal illness consisting of fever, cough, and digestive tract symptoms followed one to seven days later by encephalopathy [7, 8]. The neurological features of MERS include disturbance of consciousness, abnormal speech, delirious behavior, headache, agitation, disorientation, seizures, facial nerve paralysis, and nuchal rigidity; however visual disturbances are rare symptoms of this syndrome. The most common neurological symptom described in the literature is delirious behavior with altered consciousness, which may present as akinetic mutism [5, 9]. On MRI, MERS is almost always associated with a transient splenial lesion that is slightly hyperintense on T2- weighted images and isointense to slightly hypointense on T1-weighted images, and that shows reduced diffusion without contrast enhancement during the acute period of the disease. A classification of MERS based on MRI data was proposed; In MERS type 1, the lesions are limited to the splenium (ovoid or band shaped), as observed in our case report, whereas in MERS type 2 the lesions are not limited to the splenium [10, 11]. Clinical and radiological outcome is usually favorable with clinical improvement occurring within one to two days, while radiologic improvement within 10 days-4 months. Usually, raised serum inflammatory markers (white cell count and C-reactive protein) in the absence of CSF inflammation can be found in children diagnosed with MERS, supporting the hypothesis that this syndrome is an infection-associated encephalopathy rather than an encephalitis [7]. At the moment, No high-level evidence on the therapeutic approaches is available. Methylprednisolone pulse therapy and intravenous immune globulin (IVIG) are recommended for patients with infectious encephalopathy, regardless of pathogen or clinical-radiological syndromes [8]. Here we describe a case of MERS in an Iranian seven-year-old male patient, with a cytotoxic lesion in the SCC11Splenium of the corpus callosum detected by MRI and the unusual clinical presentation of acute bilateral blindness.Case presentationA previously healthy seven-year-old child was admitted to our hospital due to sudden-onset bilateral blindness. One day prior to admission, he suddenly developed a fever of 39 °C, cough, and loss of appetite. He was examined by his pediatrician and azithromycin and intravenous fluid therapy was prescribed due to suspected streptococcal pharyngitis. Although treatment with azithromycin and oral antipyretics was started, he still had a fever of 38 °C. On the day of admission, he experienced all at once a non-episodic bilateral blindness and delirium. The symptoms were continuous and therefore, he was admitted to the hospital emergency department. His family history was unremarkable. On physical examination, the patient was agitated associated with encephalopathy feature and his general condition was not good. The boy was collaborative during the medical evaluation, although his responsiveness was slightly impaired. Neither focal neurological signs nor meningeal irritation signs were observed.Chemistry panel and urine analysis showed no abnormalities except for a highly elevated level of CPK22Creatine phosphokinase (569 U/L), slightly elevated level of AST33Aspartate aminotransferase (47 U/L), and mild hyponatremia (134 mEq/L). The presence of blindness prompted an ophthalmologic evaluation, including a fundus oculi examination that was negative.On the following day, the electroencephalogram (EEG) showed diffuse slowing waves in favor of mild encephalopathy. The child’s neurologist observed mild increase in deep tendon reflex (DTR) but no significant focal neurological deficit was detected.The child was then admitted to perform a brain MRI and a lumbar puncture, in order to exclude acute cerebral vascular accident and the presence of viral encephalitis, cerebral abscesses, or other cerebral inflammatory lesions, such as acute disseminated encephalomyelitis (ADEM).Brain MRI was done four hours after admission and restriction in the corpus callosum was seen in diffusion-weighted imaging(DWI), with correlation in Apparent Diffusion Coefficient (ADC MAP), suggesting an abnormal diffusion restriction and a reversible cytotoxic lesion (Figure 1) Without any abnormal intensity in other views and T1-W.Treatment against suspected meningitis with intravenous ceftriaxone (100 mg/ Kg once a day), vancomycin (15 mg/ Kg every 6 h), acyclovir (10 mg/ Kg every 8 h) and dexamethasone (0.2 mg/Kg every 8 h) was initiated, while waiting for the results of the polymerase chain reaction (PCR) search for neurotropic viruses, bacteria and fungi in the cerebral spinal fluid (CSF) and peripheral blood. Antibacterial therapy was suspended because the blood and CSF44Cerebrospinal fluid culture was negative. A nasal swab for metapneumovirus virus was positive but this data did not change patient’s management.Collateral findings detected by MRI were arachnoid cyst in the posterior fossa and abnormal signal intensity in the maxillary and ethmoid sinuses. The child was in good general condition without apraxia. As a result, he was discharged after 6 days of admission and treatment with acyclovir and dexamethasone. After four days, a follow-up brain MRI was repeated, showing a complete normalization of the signal alteration in the SCC (Figure 2). The EEG was also repeated, showing a complete normalization of the pattern. The child was in good general condition, without neurological deficits.Discussion and conclusions In our case, the unusual main neurological symptom was acute bilateral blindness, which appeared after one day with symptoms suggestive of viral infection (low-grade fever, nonproductive cough). The slight metapneumovirus positivity detected by PCR in the oropharynx and nasopharynx remains a result of uncertain interpretation within the clinical picture of this patient.In this case, there are several reasons why metapneumovirus was not strongly considered in the etiology. Sometimes, a slight metapneumovirus positivity by PCR may also be found in patients without related symptoms. The seven-year-old child presented with non-specific symptoms, which could be attributed to a variety of viruses, and metapneumovirus disease usually occurs in winter and autumn. Furthermore, in this case, the PCR search for metapneumovirus in the CSF was not done.EEG abnormality was diffuse slowing in favor of mild encephalopathy and MRI imaging showed lesions limited to the splenium, which was restriction in DWI with correlation in ADC map (MERS type 1).With regard to laboratory findings, our patient had highly elevated level of CPK, slightly elevated level of AST and mild hyponatremia at hospital admission. However, this result only provides a limited contribution to the clinical presentation.Our patient was treated with intravenous therapy against suspected meningitis and herpes virus until the culture and viral PCR search for neurotropic in the blood and CSF was found to be negative. In addition, the patient received corticosteroid therapy for five days with low dose of dexamethasone. To date, there is no evidence of an effective treatment for patients with MERS, and the prognosis.In children, MERS shows a wide spectrum of clinical presentations however, visual disturbances are rare symptoms of this syndrome. Most of the MERS cases show a favorable outcome regardless of treatment. The early recognition of this condition in children with encephalopathy may limit unnecessary and potentially toxic treatments. Moreover, MERS diagnosis allows pediatricians to reassure patients’ families about the good outcome of this disease.Author contributions: Farima Farsi: writing-original draft (equal), conceptualization (equal); Shima Shekari: writing-original draft (equal), conceptualization (equal); Farah Ashrafzadeh: review and editing (equal), supervision (equal); Shima Imannezhad: review and editing (equal), visualization (equal); Ahmad Sohrab Niazi: review and editing (equal), data curation (equal); Samane Kamali: data curation (equal).Compliance with ethical standardsAcknowledgements: The authors would like to express their gratitude to Mashhad University of Medical Sciences. The authors declare that there is no conflict of interest.Data availability statement: The data, supporting this study, are available upon reasonable request from the corresponding author.Patient consent statement: Informed consent was taken from the patient and his family, that information about him would be published in a journal.ReferencesTada H, Takanashi J, Barkovich A, et al. Clinically mild encephalitis/ encephalopathy with a reversible splenial lesion. Neurology. 2004;63:1854–8.Garcia-Monco JC, Cortina IE, Ferreira E, et al. Reversible splenial lesion syndrome (RESLES): what’s in a name? J Neuroimaging. 2011;21:e1–e14.Fang Q, Chen L, Chen Q, Lin Z, Yang F. Clinically mild encephalitis/ encephalopathy with a reversible splenial lesion of corpus callosum in Chinese children. Brain and Development. 2017;39(4):321–6.Hoshino A, Saitoh M, Oka A, et al. Epidemiology of acute encephalopathy in Japan, with emphasis on the association of viruses and syndromes. Brain Dev. 2012;34(5):337-343.Vanderschueren G, Schotsmans K, Maréchal E, Crols R. Mild encephalitis with reversible splenial (MERS) lesion syndrome due to influenza B virus. Pract Neurol. 2018;18(5):391 –2.Chen W-X, Liu H-S, Yang S-D, Zeng S-H, Gao Y-Y, Du Z-H, et al. Reversible splenial lesion syndrome in children: retrospective study and summary of case series. Brain and Development. 2016;38(10):915 –27.Ka A, Britton P, Troedson C, Webster R, Procopis P, Ging J, et al. Mild encephalopathy with reversible splenial lesion: an important differential of encephalitis. Eur J Paediatr Neurol. 2015;19(3):377–82.Pan JJ, Zhao Y-Y, Lu C, Hu Y-H, Yang Y. Mild encephalitis/encephalopathy with a reversible splenial lesion: five cases and a literature review. Neurol Sci. 2015;36(11):2043 –51.Y ıld ız AE, Mara ş Genç H, Gürka ş E, Akmaz Ünlü H, Öncel İH, Güven A. Mild encephalitis/encephalopathy with a reversible splenial lesion in children. Diagn Interv Radiol. 2018;24(2):108 –12.Jea A, Vachhrajani S, Widjaja E, Nilsson D, Raybaud C, Shroff M, et al. Corpus callosotomy in children and the disconnection syndromes: a review. Childs Nerv Syst. 2008;24(6):685 –92.Takanashi J, Barkovich AJ, Shiihara T, Tada H, Kawatani M, Tsukahara H, et al. Widening spectrum of a reversible splenial lesion with transiently reduced diffusion. AJNR Am J Neuroradiol. 2006;27(4):836 –8.

INTRODUCTION Marfan syndrome (MFS) is an inherited connective tissue disease that occurs following an autosomal dominant gene mutation in the fibrillin-1gene (FBN1) 1. The protein produced by this mutated gene is an essential component of most connective tissue and being structurally abnormal, results in a wide range of specific ophthalmological, skeletal, and cardiovascular abnormalities that characterize MFS 1. The disease was discovered when Antoine - Bernard Marfan diagnosed a 5-year-old named Gabrielle who presented with skeletal signs 2. Current studies estimate the prevalence of MFS at 6.5/100,00 3. Experts, in 1986, at Berlin created the first clinical criteria for diagnosing MFS known as the Berlin Nosology 2. A new criterion was detailed in 1996 (Ghent I criteria) on account of high false positive results. In 2010 the Ghent 1 criterion was modified to include specifically FBNI mutation, aortic root dilatation, and ectopic lentis as the mainstay of MFS diagnosis (Ghent II). The formulation of this nosology was essential for the avoidance of inconclusive diagnosis and differentiation from conditions presenting with similar manifestations 1, 2. Clinical manifestations of this disorder include cardiovascular, ophthalmic, musculoskeletal, craniofacial, and cutaneous abnormalities 4. Amongst the cardiovascular manifestations, aortic dilatation and mitral regurgitation from mitral valve prolapse occur frequently5, 6.In this case report we describe the incidental finding of a young African male with classic Marfan’s syndrome but initially diagnosed at the age of 23years. We further explore the barriers to early diagnosis in our part of the world.

A document by Suman Paudel. Click on the document to view its contents.

Rationale: Fentanyl remains the primary cause of fatal overdoses, and its co-use with methamphetamine (METH) is a growing concern. The optical isomers of METH, dextromethamphetamine (d-METH) and levomethamphetamine (l-METH), differ substantially in dose expression and thus may differentially contribute to the racemate’s bidirectional effects. Furthermore, it is unknown which of METH’s monoamine (MA) receptor mechanisms mediate these respiratory effects. Thus, systematic evaluation of monoamine receptor selective agents may identify treatment targets for OIRD. Methods: The two optical isomers of METH, d-METH and l-METH, were tested in adult male mice to determine their effects on basal and fentanyl-depressed minute volume (MVb; i.e., respiratory frequency x tidal volum) using whole-body plethysmography. Next, six selective agonists at MA receptors involved in METH’s activity [phenylephrine (PNE; α1), clonidine (CLON; α2), SKF-82958 (SKF; D1), quinpirole (QPR; D2), 8-OH-DPAT (8-OH; 5HT1A), and DOI (5HT2)] were singly tested on basal MVb, and then in combination with fentanyl. Results: d-METH elevated MVb and l-METH decreased MVb. Under fentanyl-depressed conditions, the bidirectional effects of racemic METH were recreated by d-METH while l-METH significantly exacerbated OIRD at 1.0 and 3.0 mg/kg. MVb was dose-dependently increased by PNE and SKF and decreased by CLON and QPR. Neither 8-OH nor DOI altered basal MVb. Under fentanyl-depressed conditions, SKF transiently elevated MVb, while PNE more persistently increased it, while DOI transiently increased MVb, and 8-OH decreased MVb. Conclusions: d-METH and l-METH differentially contribute to the bidirectional respiratory modulation observed with the racemate and selective activation of MA receptors altered basal respiration and OIRD.

Abstract Objective This study aims to explore the spatiotemporal disparities in the equalization of basic medical and health services in China, in order to provide reference and guidance for promoting the equalization process of basic medical and health services and ensuring the fair enjoyment of citizens’ right to life and health. Methods Based on the theory of Structure-Process-Outcome(SPO), a comprehensive evaluation index system of equalization level was constructed with 22 core indicators of basic medical and health services, from the three dimensions of medical and health investment, health service utilization, and medical service effectiveness. The Generalized Principal Component Analysis (GPCA) model was used to calculate the equalization level of basic medical and health services in 31 provinces, municipalities, and autonomous regions from 2011 to 2021. Furthermore, the kernel density estimation and Moran’s I model was employed to analyze the correlation and disparity at the spatial level. Results 1. From a national perspective, the level of equalization of basic medical and health services in China has significantly improved from 2011 to 2021. The mean score of national equalization level increased from -0.605 to 0.174, with an increase of 128.75%.

The selection of chemical reactions is directly related to the quality of synthesis pathways, a reasonable reaction evaluation index plays a crucial role in the design and planning of synthesis pathways. Since the construction of traditional reaction evaluation indicators mostly rely on the structure of molecules rather than the reactions themselves, considering the impact of reaction agents poses a challenge for traditional evaluation indicators. In this study, we first propose a chemical reaction graph descriptor that includes the mapping relationship of atoms to effectively extract reaction features. Then, through pre-training using graph contrastive learning and fine-tuning through supervised learning, we establish a model for generating the probability of reaction superiority (RSscore). Finally, to validate the effectiveness of the current evaluation index, RSscore is applied in two applications: reaction evaluation and synthesis routes analysis, which proves that the RSscore provides an important agents-considered evaluation criterion for Computer-Aided Synthesis Planning (CASP).

The use of a combination of several antibacterial agents for therapy holds great promise in reducing the dosage and side effects of these agents, improving their efficiency, and inducing potential synergistic therapeutic effects. Herein, R12-AgNPs were produced with the supernatant of an ionizing radiation-tolerant bacterium Deinococcus wulumuqiensis R12 by one-step under room temperature. The biosynthesized AgNPs presented fascinating antibacterial activity and peroxidase-like properties, which endowed it with the capability to catalyse the decomposition of H2O2 to generate hydroxyl radical. After combination of R12-AgNPs and H2O2, an excellent synergistic bacteriostatic activity was observed for both E. coli and S. aureus, especially at low concentrations. In addition, in vitro cytotoxicity tests showed R12-AgNPs had good biocompatibility. Thus, this work presents a novel antibacterial agent that exhibits favorable synergistic antibacterial activity and low toxicity, without the use of antibiotics or a complicated synthesis process.

A document by Thanyathorn Nuchanatanon. Click on the document to view its contents.

Title: Diaphragmatic Extraskeletal Ewing’s Sarcoma Masquerading as Hydatid Disease: A Case Report

Fetal meconium periorchitis (MPO) is rare prenatal diagnosis associated with meconium peritonitis. The prenatal ultrasound finding consists of an enlarged fetal scrotum with echogenic fluid and debris. In this report, we describe a case in which a prenatal diagnosis of MPO was accurately made at 32 weeks of gestation. The neonate