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To investigate whether the combination of berberine and formononetin can inhibit the proliferation of nasopharyngeal carcinoma cells by regulating the MAPK/ERK signaling pathway and affecting cell autophagy. Methods: RTCA and CytationTM 5 cell imaging systems were used to detect cell proliferation. MDC staining and transmission electron microscopy were used to detect cell autophagy. Western blot was used to detect the expression levels of autophagy and proliferation-related proteins and the expression levels of key proteins in the MAPK/ERK signaling pathway. Results: The combination of berberine and formononetin can inhibit the proliferation of nasopharyngeal carcinoma cells (P < 0.05) and induce autophagy (P < 0.05) and. After berberine combined with formononetin for 24 h, the expression of LC3 II/I and Beclin1 increased, whereas the expression of P62 and PCNA decreased. The expression of key proteins p-c-Raf, p-MEK, and p-ERK1/2 in the MAPK/ERK signaling pathway was downregulated (P < 0.05). Inhibiting autophagy or activating the MAPK/ERK signaling pathway significantly reduced the effect of berberine combined with formononetin on upregulating the expression of LC3 II/I and Beclin1 and downregulating the expression of P62 and PCNA. At the same time, it significantly reduced the effects of berberine combined with formononetin in inducing autophagy and inhibiting cell proliferation (P < 0.05). Conclusion: Berberine combined with formononetin inhibits the proliferation of nasopharyngeal carcinoma cells by downregulating the activity of the MAPK/ERK signaling pathway and then upregulating LC3 II/I and Beclin1, and downregulating the expression of P62 and PCNA.

Emphysematous pyelonephritis (EPN) can be lethal and organ threatening if not recognized and treated promptly. We report a case of EPN presenting with extensive subcutaneous emphysema. A 42-year-old patient presented with severe sepsis and impending diabetic ketoacidosis. Investigations showed ruptured right EPN which resulted in pneumo-retroperitoneum, pneumo-mediastinum, and extensive subcutaneous emphysema. Emergency open retroperitoneal surgical drainage in addition to targeted antibiotics was started. Patient recovered well clinically and radiologically without a need for nephrectomy. Prompt diagnosis and timely treatment are of utmost importance. Clinical suspicion should be heightened in at-risk patients who present in sepsis state with a diagnosis of pyelonephritis or those who are not responding to the routine management of pyelonephritis.

Case series Patients: Male, 39-year-old (age at diagnosis) • Male, 62-year-old (age at diagnosis) Final Diagnosis: Fabry disease Symptoms: Corneal verticillata • kidney failure • neuropathy • proteinuria Medication: — Clinical Procedure: — Specialty: Genetics • Hematology • Laboratory Diagnostics • Nephrology • Neurology • Ophthalmology Objective: Rare disease Background: No cases of Fabry disease (FD) have been reported thus far in Malaysia. We aimed to report the demographic characteristics, clinical manifestations, molecular results, and treatment outcomes of 2 FD cases. This study was a retrospective review of 2 family clusters of FD on follow-up in Sarawak, Malaysia. Case Reports: Two index patients were confirmed to have FD. Index patient 1, who had nephrotic-range proteinuria and cornea verticillata, carried a variant within exon 4 of the GLA gene: c.610 T>C (p.Trp204Arg). Agalsidase beta (Fabrazyme®) enzyme replacement therapy was initiated, with the absence of neutralizing antibody after 24 months. No hypersensitivity or adverse reactions were reported. The patient’s proteinuria and renal function remained stable. Other family members who carried the same mutation were asymptomatic. Index patient 2, who had residual activity of α-galactosidase A and a normal globotriaosylsphingosine level, carried a novel GLA mutation of c.548-5T>A. He was diagnosed with end-stage renal disease on regular dialysis and had nonspecific headache with 1 episode of seizure a few years prior to FD genetic screening. One brother had chronic neuropathic pain but refused further investigations. Other family members who had the same mutation were asymptomatic. This mutation has never been reported in literature, and its pathogenicity warrants further studies. Conclusions: It is of utmost importance to increase awareness of FD among clinicians, so that appropriate screening may be done to determine its true prevalence and prompt treatment can be initiated early.

Mucoceles of the paranasal sinus commonly involve the frontal sinuses, the ethmoid sinuses, and rarely the maxillary or sphenoid sinuses. They often present with sinus pain or pressure, but rarely can present with more severe symptoms such as changes in mental status or vision due to expansion and invasion through the skull base or orbit. A 62-year-old male presented with optic neuropathy, a relative afferent pupillary defect with proptosis and lateral gaze palsy of the left eye. The patient was found to have a large mucocele extending from the left posterior ethmoid sinus into the left orbital apex. Urgent endoscopic sinus surgery was performed jointly between Oculoplastics and Otolaryngology. Post-operatively, the patient had improvement in diplopia, extraocular motion, and proptosis with stable vision. This case demonstrates the importance of early identification and intervention in a rare presentation of a sinus mucocele to prevent serious complications such as vision loss.

Background Adiponectin (ADIPOQ) is an important factor involved in the regulation of both carbohydrate and lipid metabolism. Polymorphisms in the ADIPOQ gene are known to influence an individual's predisposition to metabolic syndrome and type 2 diabetes. Moreover, women with gestational diabetes mellitus (GDM) are at an increased risk of developing type 2 diabetes. Several studies have been conducted previously to assess the association between ADIPOQ polymorphisms and GDM; however, the results of the association are inconclusive. Aim To quantitatively evaluate the association between ADIPOQ +45T/G, +276G/T, and -11377C/G polymorphisms and the risk of GDM. Methods A systematic search of EMBASE, PubMed, CNKI, Web of Science, and WANFANG DATA was conducted up to October 20, 2018. We calculated merged odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed-effects or random-effects model depending on the between-study heterogeneity to evaluate the association between AIDPOQ +45T/G, +276G/T, and -11377C/G polymorphisms and the risk of GDM. Subgroup analysis was performed by ethnicity. Publication and sensitivity bias analyses were performed to test the robustness of the association. All statistical analyses were conducted using Stata12.0. Results Nine studies of +45T/G included 1024 GDM cases and 1059 controls, five studies of +276G/T included 590 GDM cases and 595 controls, and five studies of -11377C/G included 722 GDM cases and 791 controls. Pooled ORs indicated that +45T/G increased GDM risk in Asians (allelic model: OR = 1.47, 95%CI: 1.27-1.70, P = 0.000; dominant model: OR = 1.54, 95%CI: 1.27-1.85, P = 0.000; recessive model: OR=2.00, 95%CI: 1.43-2.85, P = 0.000), not in South Americans (allelic model: OR = 1.21, 95%CI: 0.68-2.41, P = 0.510; dominant model: OR = 1.13, 95%CI: 0.59-2.15, P = 0.710; recessive model: OR = 2.18, 95%CI: 0.43-11.07, P = 0.350). There were no significant associations between +276G/T (allelic model: OR = 0.88, 95%CI: 0.74-1.05, P = 0.158; dominant model: OR = 0.91, 95%CI: 0.65-1.26, P = 0.561; recessive model: OR = 0.82, 95%CI: 0.64-1.05, P = 0.118) or -11377C/G (allelic model: OR = 0.96, 95%CI: 0.72-1.26, P = 0.750; dominant model: OR = 1.00, 95%CI: 0.73-1.37, P = 0.980; recessive model: OR = 0.90, 95%CI: 0.61-1.32, P = 0.570) and the risk of GDM. Conclusion Our meta-analysis shows the critical role of the ADIPOQ +45T/G polymorphism in GDM, especially in Asians. Studies focused on delineating ethnicity-specific factors with larger sample sizes are needed.

Patient: Female, 22-year-old Final Diagnosis: Lepromatous leprosy co-infected with melioidosis • complicated by dapsone-induced methaemoglobinaemia and type 2 lepra reaction Symptoms: Cyanosis • fever • jaundice • pallor • skin rash Medication: — Clinical Procedure: — Specialty: Dermatology • Hematology • Infectious Diseases • General and Internal Medicine • Microbiology and Virology Objective: Unusual clinical course Background: Leprosy is an infection caused by Mycobacterium leprae. An extensive literature search did not reveal many reports of melioidosis in association with leprosy. Case Report: A 22-year-old woman, who was diagnosed with multibacillary leprosy, developed dapsone-induced methemoglobinemia and hemolytic anemia, complicated by melioidosis. Methemoglobinemia was treated with methylene blue and vitamin C. Two weeks of ceftazidime was initiated to treat melioidosis, and the patient was discharged on amoxicillin/clavulanic acid and doxycycline as melioidosis eradication therapy. However, she developed drug-induced hypersensitivity. Trimethoprim/sulfamethoxazole, as an alternative treatment for melioidosis eradication, was commenced and was successfully completed for 12 weeks. During the fifth month of multidrug therapy, the patient developed type II lepra reaction with erythema nodosum leprosum reaction, which was treated with prednisolone. Leprosy treatment continued with clofazimine and ofloxacin, and complete resolution of skin lesions occurred after 12 months of therapy. Conclusions: Our case highlighted the challenges posed in managing a patient with multibacillary leprosy with multiple complications. Clinicians should be aware that dapsone-induced methemoglobinemia and hemolysis might complicate the treatment of leprosy. Our case also highlighted the safety and efficacy of combining ofloxacin and clofazimine as a leprosy treatment regimen in addition to gradual steroid dose titration in the presence of type II lepra reaction.

With the continuous development and application of targeted drugs, it is particularly desirable to find a non-invasive diagnostic approach to screen patients for precision treatment. Specifically, detection of multiple cancer-related mutations is very important for targeted therapy and prediction of drug resistance. Although numerous advanced PCR methods have been developed to discriminate single nucleotide polymorphisms, their drawbacks significantly limit their application, such as low sensitivity and throughput, complicated operations, and expensive costs. In order to overcome these challenges, in this study, we developed a method combining multiplex and sensitive real-time PCR assay with rolling circle amplification. This allows specific and sensitive discrimination of the single nucleotide mutation and provides convenient multiplex detection by real-time PCR assay. The clinical potential of the MPRP assay was further demonstrated by comparing samples from 8 patients with a digital PCR assay. The coincident results between these two methods indicated that the MPRP assay can provide a specific, sensitive, and convenient method for multiplex detection of cancer-related mutations.

This paper is dedicated to Andrew Price Smith for his extensive analysis of the impact of the 1918 influenza and for being the first to investigate the Austrian Spanish Influenza Archives to demonstrate that the virus struck the Axis troops prior to the Alliance, which forced Kaiser to opt for peace. The COVID-19 pandemic has altered the lives of people around the world, with significant death toll in addition to global social, political and economic impact. Many people have wondered how it compares to the seasonal influenza and prior pandemics. In order to better understand and manage the current pandemic, it is useful to compare it to historical pandemics, such as the Spanish influenza of 1918.1 The 1918 Spanish influenza is caused by an H1N1 influenza A virus postulated to be of avian origin.2 The 1918 Spanish influenza lasted from 1918 to 1920 and consisted of four waves. The first wave lasted approximately from 15 February 1918 to 1 June 1918; the second lasted approximately from 1 August 1918 to 2 December 1918; the third lasted approximately from 3 December 1918 to 30 April 1919; and the fourth wave lasted approximately from 1 December 1919 to 30 April 1920.3 It infected about 500 million people, roughly one-third of the world’s population at that time, and resulted in the deaths of 50 million, including 675 000 Americans.2 The first public news of the epidemic appeared in Madrid on 22 May 1918 in Madrid’s ABC newspaper; hence, it became known as the Spanish influenza.4 However, there is no definite evidence of origination, and most epidemiologists and virologists believe that the virus originated in either the USA or France.4 A week later on 28 May 1918, King Alfonso XIII, the Prime Minister and some cabinet members became …

A 65-year-old gentleman with claudication underwent contrast-enhanced computed tomography. The scan showed occlusion of the infrarenal abdominal aorta and a 6.0 × 3.7 cm saccular zone-3 arch aneurysm. The left ventricular ejection fraction was 35% and a coronary angiogram revealed triple-vessel disease. In view of the patient’s high risk with EuroSCORE II 20.34%, coronary artery surgery was combined with hybrid type I arch aneurysm repair. An endovascular stent was delivered in an antegrade manner. Open heart surgery and a hybrid type I arch intervention can be performed simultaneously through a midline sternotomy approach.

Background We investigated the activity of loureirin B against liver fibrosis and the underlying molecular mechanisms. Methods Hepatic stellate cells (HSCs) from Sprague-Dawley rats were treated with different concentrations of loureirin B. We used the MTT assay to determine HSC proliferation, flow cytometry to analyze apoptosis, and western blot to determine the expressions of Bax, Bcl-2, Wnt1 and β-catenin. Real-time PCR was used to determine the expressions of Wnt1 and miR-148-3p. Results The MTT assay showed that loureirin B treatment significantly inhibited the proliferation of HSCs in time- and dose-dependent manners. Loureirin B significantly promoted the apoptosis of HSCs, increased the expression of Bax and decreased the Bcl-2 level. Western blot analysis showed that the expressions of Wnt1 and β-catenin were obviously lower in the loureirin B treatment group than in the control group. We also found that loureirin B could decrease the Wnt1 mRNA level and increase miR-148-3p expression. Knockdown of miR-148-3p using inhibitor could reverse the effects of loureirin B on the proliferation and apoptosis of HSCs and the expressions of Bax, Bcl-2, Wnt1 and β-catenin. Conclusion Our results suggest that loureirin B inhibited the proliferation and promoted the apoptosis of HSCs, and suppressed the Wnt/β-catenin signaling pathway via regulation of miR-148-3p.

The array of comorbidities that comes with obesity and the propelling surge of this disease globally today make the urgent need for treatment vital. Although promoting a healthy physical regimen and controlled diet to affected patients are the main bulk of present treatment, prescriptions of weight-loss medications have also been introduced to complement this treatment. However, the use of synthetic medications may produce adverse side effects and consequently affect the patient's quality of life. In view of these problems, the use of natural sources as alternative remedies has recently become very popular. Tropical fruit "waste components", namely, the seed, flower, leaf, peel, and part of the fruit, which are often discarded after consumption, have recently been studied and showed evidence suggesting their potential as promising future alternative sources of remedy. The high amounts of phytochemicals present in these components were believed to be responsible for the antiobesity effect observed experimentally. This review aims to introduce some of the recently discussed tropical fruit waste components that have been discovered to possess antiobesity effects. The major bioactive compounds of the respective fruit components identified and deduced to be responsible for the overall bioactivity will be evaluated. Following this, the subsequent need for the development of an effective processing or recycling technique required to effectively tap the maximum potential of these fruit parts will also be addressed.

Adipocyte dysfunction is a major cause of obesity, which is associated strongly with many disorders including psychological and medical morbidities, metabolic abnormalities, and cardiovascular diseases as well as a series of cancers. This study investigated the antiadipogenic activity of scutellarin (1) in 3T3-L1 preadipocytes as well as the underlying molecular mechanisms. It was observed that 1 reduced adipocyte differentiation of 3T3-L1 cells potently, as evidenced by a decrease in cellular lipid accumulation. At the molecular level, mRNA expression of the master adipogenic transcription factors, PPARγ and C/EBPα, was decreased markedly. However, mRNA levels of C/EBPβ, the upstream regulator of PPARγ and C/EBPα, were not decreased by 1. Moreover, a dose-dependent upregulation of PPARα was observed for 1. Computational modeling indicated that 1 can bind to PPARα, γ, and δ each in a distinct manner, while it can activate PPARα only by forming a hydrogen bond with Y464, thus stabilizing the AF-2 helix and activating PPARα. Therefore, these results suggest that 1, a major component of Scutellaria baicalensis, attenuates fat cell differentiation by upregulating PPARα as well as downregulating the expression of PPARγ and C/EBPα, thus showing therapeutic potential for obesity-related diseases.

Minimal hepatic encephalopathy (MHE) is caused by dysbiosis of gut microbiota, particularly the ammonia-producing bacteria. Given the efficacy of certain treatments on MHE and the connection between alcoholism and MHE, a thorough understanding of how these strategies affect the gut microbiota in patients (alcoholic or non-alcoholic) will facilitate the assessment of their efficacy in the reshaping of gut microbiota. In the present study, a metagenomics approach was adopted to reveal alterations in gut microbiota of 14 MHE patients following treatment with rifaximin alone or rifaximin plus probiotics. Patients were grouped into the alcoholic and non-alcoholic groups to examine differences in terms of their response to treatment. Treatment reduced the overall microbiota diversity and decreased the abundance of certain ammonia-producing bacteria, such as Clostridium, with the treatment of rifaximin plus probiotics presenting a more apparent effect. Non-alcoholic MHE patients responded better to the treatment, as they presented greater reduction in microbiota diversity and a more consistent decline in certain ammonia-producing bacteria genera (such as Clostridium and Streptococcus) belonging to the Firmicutes phylum. In conclusion, treatment with rifaximin alone and rifaximin plus probiotics exhibited a different effect in different MHE patients, decreasing the overall gut microbiota diversity to various extents and reshaping microbiota in different ways. Furthermore, non-alcoholic MHE patients responded better to treatment in microbiota alterations.

Proliferation and invasion of cancer cells require favorable pH, yet potentially toxic quantities of acid are produced metabolically. Membrane-bound transporters extrude acid from cancer cells, but little is known about the mechanisms that handle acid once it is released into the poorly-perfused extracellular space. Here, we studied acid-handling by stromal myofibroblasts (colon cancer-derived Hs675.T, intestinal InMyoFib, embryonic colon-derived CCD-112-CoN), skin fibroblasts (NHDF-Ad) and colorectal cancer (CRC) cells (HCT116, HT29) grown in mono- or co-culture. Expression of the acid-loading transporter anion exchanger 2 (AE2; SLC4A2 product) was detected in myofibroblasts and fibroblasts, but not in CRC cells. Compared to CRCs, Hs675.T and InMyoFib myofibroblasts had very high capacity to absorb extracellular acid. Acid-uptake into CCD-112-CoN and NHDF-Ad cells was slower and comparable to levels in CRCs, but increased alongside SLC4A2 expression under stimulation with transforming growth factor β1 (TGFβ1), a cytokine involved in cancer-stroma interplay. Myofibroblasts and fibroblasts are connected by gap junctions formed by proteins such as connexin-43 which allows the absorbed acid-load to be transmitted across the stromal syncytium. To match the stimulatory effect on acid-uptake, cell-to-cell coupling in NHDF-Ad and CCD-112-CoN cells was strengthened with TGFβ1. In contrast, acidtransmission was absent between CRCs, even after treatment with TGFβ1. We propose that the juxtaposition of an acid-absorbing myofibroblast syncytium and acid-producing CRCs improves the flow of acid through solid tumors. Importantly, the activities of stromal AE2 and connexin-43 do not place an energetic burden on cancer cells, allowing resources to be diverted for other biological functions such as growth.

Four up-flow anaerobic sludge blanket reactors (UASB) filled with oyster shell (R1), activated carbon (R2), quartz sand (R3), zeolite (R4), respectively had been selected to inspect their effects on the COD removal efficiency, and to compare with the traditional UASB reactor (R0). System stability and pH variation were also inspected. All the reactors were inoculated with sludge from a local sewage treatment plant, and fed with the synthetic wastewater. The organic load rate was 0.96 kgCOD.m-3.d-1during 1-20 days (StageⅠ), 1.86 kgCOD.m-3.d-1during 21-57 days(StageⅡ), and 5.32 kgCOD.m-3.d-1during 58-97 days(StageⅢ), the system temperature was controlled at 35 °C. The influent pH was 7-8. The results reveal that: (1) The average removal rate was 94.5%, 78.0%, 91.4% for R1; 93.6%, 87.7%, 92.5% for R2in the three stages, respectively. R1and R2reactors are suitable to treat low organic load wastewater( 0.96 kgCOD.m-3.d-1) to high organic load wastewater(5.32 kgCOD.m-3.d-1). R3, R4and R0are not suitable for high organic load wastewater. (2) R1and R2reactors can resist the continuous organic shock load, and the system can recover in a short time; R3, R4and R0reactors could not recover during StageⅢ. (3) The system was sensitive to temperature variation, so temperature was an important factor to the system. (4) Anaerobic granular sludge were formed in R1, R2, R3, R4reactors, the amount of granular sludge sequencing was 89.02%, 82.46%, 16.44%, 36.54%, respectively. Compared to the support material size which was 0.15-0.20 mm; the size of granular sludge larger than 0.90mm was 41.5% in R1reactor, and 28.8% in R2reactor. (5) All the reactors had the ability of pH value moderation, so the pH value of all the system were stable. Since oyster shell is a solid waste, oyster shell powder used as the immobilization material not only has good effects of immobilization, but also has a strong economic competitiveness.

To investigate patterns of grief and depression in a sample of parents whose child had died of cancer, and to examine factors related to burden of illness and end-of-life care as potential predictors of parental grief and depression outcomes.Fifty-eight parents completed standardized self-report questionnaires measuring prolonged grief disorder (Inventory of Complicated Grief-Revised [ICG-R]) and depression (Beck Depression Inventory-Second Edition [BDI-II]) and participated in structured interviews designed to elicit their perceptions of their child's end-of-life care and burden of illness. The majority of participants were mothers (84%) and the mean length of time since child death was 4.5 (standard deviation [SD] = 2.4) years (range, 1.0-9.8 years).Rates of prolonged grief disorder (PGD) were similar to those reported in other bereaved populations (10.3%); however, 41% of parents met diagnostic criteria for grief-related separation distress. Twenty-two percent of parents reported clinically significant depressive symptoms. Time since death and parental perception of the oncologist's care predicted parental grief symptoms but not depressive symptoms. Perceptions of the child's quality of life during the last month, preparedness for the child's death, and economic hardship also predicted grief and depression outcomes.A minority of parents met criteria for PGD and depression, however, almost half the sample was experiencing significant separation distress associated with persistent longing and yearning for their child. Time since death is a significant predictor of parental psychological distress. This study also highlights the importance of end-of-life factors in parents' long-term adjustment and the need for optimal palliative care to ensure the best possible outcomes for parents.

Summary Background Staphylococcus aureus has a peculiar ability to colonize the skin of patients with eczema and atopic dermatitis (AD), and is consistently found in eczematous skin lesions in these patients. A correlation between the severity of the eczema and colonization with S. aureus has been demonstrated, and it has been determined that bacterial colonization is an important factor aggravating skin lesions. Patients colonized with S. aureus have been treated with antibiotics in several open and double-blind placebo-controlled studies, with conflicting results. Objectives To investigate the colonizing features of S. aureus in the lesional and nonlesional skin of patients with eczema and AD in China and to compare the therapeutic effect of mupirocin plus hydrocortisone butyrate with vehicle ointment plus hydrocortisone butyrate. Methods A multicentre, double-blind randomized trial was conducted. Eczema Area and Severity Index (EASI) scores were evaluated before the start of the trial and on the 7th, 14th and 28th day of treatment. Swabs for bacterial isolation were taken from lesional skin before the start of the trial and on the 7th, 14th and 28th day of treatment, and from nonlesional skin only before the start of the trial. A combination topical therapy with mupirocin plus hydrocortisone butyrate ointment was used in the experimental group, with vehicle ointment plus hydrocortisone butyrate ointment as a control. Results Of 327 patients enrolled in the study, 208 had eczema and 119 had AD. Bacteria were isolated from 70·2% of lesional and 32·7% of nonlesional skin samples from patients with eczema, of which S. aureus accounted for 47·3% and 27·9%, respectively. Bacteria were isolated from 74·8% of lesional and 34·5% of nonlesional skin samples from patients with AD, of which S. aureus accounted for 79·8% and 80·5%, respectively. The colonization density of S. aureus was markedly higher in lesional than in nonlesional skin, both in patients with eczema and with AD (P 0·05). However, in patients with eczema with a clinical score of > 8 or in patients with AD with a clinical score of > 7, the therapeutic effect in the experimental groups was superior to that in the control groups (P 0·05). Following the improvement of symptoms and signs of eczema and AD, the positive rates of bacteria and S. aureus were reduced on the 7th day of treatment. Conclusions This study confirmed that lesional skin of patients with eczema and AD was more frequently colonized with S. aureus than was nonlesional skin. The more severe the eczema, the higher the colonization rate of S. aureus, and S. aureus was also more often present in lesional and nonlesional skin in patients with AD than in those with eczema. Staphylococcus aureus infection is related to the pathogenesis of eczema and AD. An antibiotic–corticosteroid combination and corticosteroid alone both gave good therapeutic effect in eczema and in AD, and both reduced colonization by S. aureus. Early combined topical therapy is beneficial to patients with moderate to severe eczema and AD, and it is unnecessary to use antibiotics at later stages of disease or in mild eczema or AD.

Dual versus single antiplatelet treatment in very elderly patients with acute myocardial infarction (AMI) is under-studied. This study sought to examine the effectiveness of single antiplatelet therapy in real-world, medically managed elderly patients with AMI. The retrospective cohort study

The age-related loss of accommodation (presbyopia) in human and nonhuman primates clearly involves loss of deformability of the crystalline lens. In addition, ciliary muscle mobility, as measured by both histologic1,2 and ultrasonographic (monkey)3 and magnetic resonance (human)4 imaging techniques, also diminishes with age. However, the isolated ciliary muscle in nonhuman primates maintains its full ability to contract in response to appropriate pharmacologic stimulation throughout life,1,2,5 and its contractile machinery and receptor biology also remain normal.6,7 Therefore, posterior restriction of muscle movement in the aging eye has been hypothesized to play a role in the pathophysiology of presbyopia as well, at least in monkeys.8 In addition, there are zonular attachments to the vitreous membrane in both species that have not yet been fully investigated. Earlier studies were focused mainly on the anterior hyaloid membrane. Wieger9 was among the first to describe attachments of the zonules to the anterior vitreous membrane. They were later termed Wieger's ligament.10–12 Streeten and Pulaski13 doubted the strength of Wieger's ligament, because, after lens extraction, it is not uncommon for a superficial flap of either the capsule or anterior hyaloid to be torn from Wieger's area.13 Bernal et al.,14 using a combination of environmental scanning electron microscopy (ESEM) combined with a custom-made manual lens stretcher to facilitate inside microscopy, were able to further analyze the complex connection between the anterior vitreous membrane and zonule.14 Attachments between the posterior pars plana zonule and the vitreous membrane have been observed in histologic sections and by SEM.15–17 Improved in vivo imaging by ultrasound biomicroscopy (UBM) allows visualization of zonular fibers in the living eye.18 Using UBM, we observed a straight line parallel to but separated from the pars plana by a cleft approximately 2 mm wide, extending from the region of the ciliary processes to the region of the ora serrata (see Fig. 1). There has been debate as to whether the structure observed by UBM was (1) the pars plana zonule, which in the living eye is normally separated from the pars plana ciliary epithelium, but after fixation for histology or air drying for scanning electron microscopy (SEM) becomes apposed to the pars plana ciliary epithelium (CE)19; (2) the vitreous membrane20; or (3) another component of the vitreozonular system that has not been well described or characterized. Figure 1. UBM overview image in a live rhesus monkey shows a prominent straight line (arrow) extending from the pars plicata region of the ciliary body to the ora serrata region and separated from the pars plana epithelium by a cleft. CP, ciliary processes, CB, ... We investigated the zonule, the posterior vitreous, and their attachments by novel scanning SEM and UBM techniques, and we now can hypothesize about how this system may affect ciliary muscle movement. In addition, we provide preliminary physiological evidence that ciliary muscle movement may be increased by perturbing the system.