Preventing Post-Lumbar Puncture Headache.

Post-lumbar puncture headache is the main adverse event from lumbar puncture and occurs in 3.5% to 33% of patients, causing functional and socio-professional disability. We searched the post-lumbar puncture headache literature and, based on this review and personal expertise, identified and addressed 19 frequently asked questions regarding post-lumbar puncture headache risk factors and prevention. Among the nonmodifiable factors, older age is associated with a lower incidence of post-lumbar puncture headache, while female sex, lower body mass index, and history of headache might be associated with increased risk. The use of atraumatic, noncutting needles is the most effective intervention for post-lumbar puncture headache prevention. These needles are not more difficult to use than cutting needles. Other commonly recommended measures (eg, fluid supplementation, caffeine) appear unhelpful, and some (eg, bed rest) may worsen post-lumbar puncture headache.

IS THE NEW PROCORE 20G DOUBLE FORWARD-BEVEL NEEDLE CAPABLE TO OBTAIN BETTER HISTOLOGICAL SAMPLES BY ENDOSCOPIC ULTRASOUND FOR DIAGNOSING SOLID PANCREATIC LESIONS?

BACKGROUND: Fine needle biopsy (FNB) histological samples by endoscopic ultrasound. It is important to obtain representative histological samples of solid biliopancreatic lesions without a clear indication for resection. The role of new needles in such task is yet to be determined. AIM: To compare performance assessment between 20G double fine needle biopsy (FNB) and conventional 22G fine needle aspiration (FNA) needles for endoscopic ultrasound (EUS)-guided biopsy. METHODS: This prospective study examined 20 patients who underwent the random puncture of solid pancreatic lesions with both needles and the analysis of tissue samples by a single pathologist. RESULTS: The ProCore 20G FNB needle provided more adequate tissue samples (16 vs. 9, p=0.039) with better cellularity quantitative scores (11 vs. 5, p=0.002) and larger diameter of the histological sample (1.51±1.3 mm vs. 0.94±0.55 mm, p=0.032) than the 22G needle. The technical success, puncture difficulty, and sample bleeding were similar between groups. The sensitivity, specificity, and diagnostic accuracy were 88.9%, 100%, and 90% and 77.8%, 100%, and 78.9% for the 20G and 22G needles, respectively. CONCLUSIONS: The samples obtained with the ProCore 20G FNB showed better histological parameters; although there was no difference in the diagnostic performance between the two needles, these findings may improve pathologist performance.

Influenza Vaccines toward Universality through Nanoplatforms and Given by Microneedle Patches.

Influenza is one of the top threats to public health. The best strategy to prevent influenza is vaccination. Because of the antigenic changes in the major surface antigens of influenza viruses, current seasonal influenza vaccines need to be updated every year to match the circulating strains and are suboptimal for protection. Furthermore, seasonal vaccines do not protect against potential influenza pandemics. A universal influenza vaccine will eliminate the threat of both influenza epidemics and pandemics. Due to the massive challenge in realizing influenza vaccine universality, a single vaccine strategy cannot meet the need. A comprehensive approach that integrates advances in immunogen designs, vaccine and adjuvant nanoplatforms, and vaccine delivery and controlled release has the potential to achieve an effective universal influenza vaccine. This review will summarize the advances in the research and development of an affordable universal influenza vaccine.

Current status of newer generation endoscopic ultrasound core needles in the diagnostic evaluation of gastrointestinal lesions.

Endoscopic ultrasound-guided tissue acquisition is now an imperative technique for the diagnosis of multiple diseases in the gastrointestinal tract and nearby structures. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and fine needle biopsy via dedicated FNB needles (EUS-FNB) are two standard-essential tools for tissue acquisition. The choice of needle type is an important factor determining appropriate tissue acquisition. Multiple studies have compared EUS-FNA versus EUS-FNB on different lesions also there are several studies evaluated different needles in terms of sampling adequacy and cytological and histological accuracy. Prior studies comparing prior-generation FNB needles to FNA did not show an increased diagnostic yield with FNB. However, the newer-generation needles have demonstrated enhanced performance compared with their predecessors. As they may provide a large amount of tissue for the cytological and histological evaluation, rapid onsite specimen evaluation (ROSE), and immunohistochemical and molecular analyses, which may be very important for targeted therapy. In this review, we discuss current evidence and literature on the use of the newer generation needles for pancreatic and non-pancreatic lesions.

Small core needle biopsies in cytology practice: a survey of members of the American Society of Cytopathology.

INTRODUCTION: The introduction of a new generation of core needle biopsies (CNBs) for endoscopic procedures has prompted reconsideration of the role of cytopathologists in the handling of small biopsies. The American Society of Cytopathology (ASC) has therefore conducted a survey with the intention of elucidating current practices regarding the handling of small CNBs. MATERIALS AND METHODS: The membership of the ASC was invited by email to participate in an online survey over a 2-month period. The survey consisted of 20 multiple choice questions with 2-8 possible responses per question. RESULTS: Of 2651 members contacted by e-mail, 282 (10.6%) responded to the survey questions, including 196 pathologists (69.5%) and 86 cytotechnologists (30.5%). Of these, 265 respondents were from the US/Canada (94.0%), with 156 from academic institutions (58.9%) and 109 from non-academic practices (41.1%); 17 were from other countries (6.0%). In 18.8% of all practices, cytopathologists sign out >90% of small CNBs from endoscopic and radiologically guided procedures; in 36.5% of practices >90% are signed out by surgical pathologists; the remainder have such cases divided more evenly between cytopathologists and surgical pathologists. Responses show that 78.0% of all respondents are interested in signing out more small biopsies in the future, and 80.5% desire increased small biopsy-related resources from the ASC. CONCLUSIONS: The survey responses indicate that practices currently vary widely across institutions. Most indicated an interest in greater incorporation of small biopsies into the practice of cytopathology.

Purchase data: a proxy for safety status.

This study demonstrated the use of purchase data to determine the incidence of sharps injuries in a major tertiary referral hospital in Australia. The incidence rates of injuries per 100,000 items purchased were 2.65 and 12.60 for syringe needles and scalpel blades, respectively. These figures were lower than those reported previously using this method. The incidence rate for injuries with suture needles, which had not been reported previously, was 31.89/100,000 items purchased. Incidence data calculated in this manner may be used in conjunction with purchase cost estimates to inform policy and practices on institutional staff safety measures.

Gelatin Methacryloyl Microneedle Patches for Minimally Invasive Extraction of Skin Interstitial Fluid.

The extraction of interstitial fluid (ISF) from skin using microneedles (MNs) has attracted growing interest in recent years due to its potential for minimally invasive diagnostics and biosensors. ISF collection by absorption into a hydrogel MN patch is a promising way that requires the materials to have outstanding swelling ability. Here, a gelatin methacryloyl (GelMA) patch is developed with an 11 × 11 array of MNs for minimally invasive sampling of ISF. The properties of the patch can be tuned by altering the concentration of the GelMA prepolymer and the crosslinking time; patches are created with swelling ratios between 293% and 423% and compressive moduli between 3.34 MPa and 7.23 MPa. The optimized GelMA MN patch demonstrates efficient extraction of ISF. Furthermore, it efficiently and quantitatively detects glucose and vancomycin in ISF in an in vivo study. This minimally invasive approach of extracting ISF with a GelMA MN patch has the potential to complement blood sampling for the monitoring of target molecules from patients.

Is the new procore 20g double forward-bevel needle capable to obtain better histological samples by endoscopic ultrasound for diagnosing solid pancreatic lesions? / A nova agulha procore 20g com bisel frontal duplo é capaz de obter melhores amostras histológicas por ecoendoscopia no diagnóstico de lesões sólidas pancreáticas?

ABSTRACT Background: It is important to obtain representative histological samples of solid biliopancreatic lesions without a clear indication for resection. The role of new needles in such task is yet to be determined. Aim: To compare performance assessment between 20G double fine needle biopsy (FNB) and conventional 22G fine needle aspiration (FNA) needles for endoscopic ultrasound (EUS)-guided biopsy. Methods: This prospective study examined 20 patients who underwent the random puncture of solid pancreatic lesions with both needles and the analysis of tissue samples by a single pathologist. Results: The ProCore 20G FNB needle provided more adequate tissue samples (16 vs. 9, p=0.039) with better cellularity quantitative scores (11 vs. 5, p=0.002) and larger diameter of the histological sample (1.51±1.3 mm vs. 0.94±0.55 mm, p=0.032) than the 22G needle. The technical success, puncture difficulty, and sample bleeding were similar between groups. The sensitivity, specificity, and diagnostic accuracy were 88.9%, 100%, and 90% and 77.8%, 100%, and 78.9% for the 20G and 22G needles, respectively. Conclusions: The samples obtained with the ProCore 20G FNB showed better histological parameters; although there was no difference in the diagnostic performance between the two needles, these findings may improve pathologist performance.

RESUMO Racional: As lesões sólidas pancreáticas não ressecáveis cirurgicamente demandam boa amostragem tecidual para definição histológica e condução oncológica . O papel das novas agulhas de ecopunção no aprimoramento diagnóstico ainda necessita elucidação. Objetivo: Comparar as biópsias guiadas por ecoendoscoopia com a nova agulha 20G de bisel frontal duplo (FNB) com a agulha de aspiração fina 22G convencional. Métodos: Este estudo prospectivo avaliou 20 pacientes submetidos à punção de lesões pancreáticas sólidas com ambas agulhas e envolveu análise de amostras teciduais por um único patologista. Resultados: A agulha FNB 20G forneceu amostras de tecido mais adequadas (16 vs. 9, p=0,039) com melhores escores quantitativos de celularidade (11 vs. 5, p=0,002) e maior diâmetro máximo da amostra histológica (1,51±1,3 mm vs. 0,94±0,55 mm, p=0,032) que a agulha 22G. O sucesso técnico, dificuldade de punção e sangramento da amostra foram semelhantes entre os grupos. A sensibilidade, especificidade e acurácia diagnóstica foram 88,9%, 100% e 90% e 77,8%, 100% e 78,9% para as agulhas 20G e 22G, respectivamente. Conclusão: As amostras obtidas com a FNB 20G apresentaram melhores parâmetros histológicos, embora não tenha havido diferença no desempenho diagnóstico entre as duas agulhas.

Effects of needle gauge and syringe size on small intestinal leakage at injection sites.

OBJECTIVE: To determine the influence of needle gauge, syringe volume, and syringe size on needle tract leakage after injection in porcine jejunum. STUDY DESIGN: Ex vivo experiment. SAMPLE POPULATION: Three hundred sixty jejunal segments from 20 feedlot pigs. METHODS: Fresh porcine intestines were divided into 5-cm or 10-cm segments and randomly assigned to the one of nine treatment groups: 25-gauge, 22-gauge, and 20-gauge needles attached to full 12-mL, half-full 20-mL, and full 20-mL syringes (n = 20/group). The jejunal segments were occluded with Rochester-Carmalt forceps prior to injection of diluted India ink. Injection time and leakage were noted by a blinded observer. Multivariate analysis was used with segment size, needle gauge, volume infused, time to inject per milliliter, and syringe size as variables. RESULTS: Leakage occurred in 36% of 5-cm and 15% of 10-cm segments and was immediate without palpation in 33.8% and 11% of segments, respectively. Protective effects were seen for 22-gauge needles in both 5-cm (P = .002) and 10-cm (P = .001) segments, whereas injection of 20 mL had a higher odds ratio of leakage compared with injection of 10 mL and 12 mL in 5-cm segments (P = .003). CONCLUSION: Injections with 22-gauge needles reduced the frequency of leakage, while 20 mL instilled in 5-cm segments increased the frequency of leakage in intact segments of porcine jejunum. CLINICAL SIGNIFICANCE: Injection with a smaller syringe size attached to a 22-gauge needle through a 10-cm segment of small intestine may lower the frequency of leakage from the injection site, but influence on the detection of surgical site leakage remains unknown.

A acupuntura na percepção de indivíduos com hipertensão arterial atendidos em uma unidade de pronto atendimento / Acupuncture in the perception of hypertensive individuals in an emergency medical unit

A hipertensão arterial sistêmica (HAS) é uma condição clínica multifatorial caracterizada por níveis elevados e sustentados de pressão arterial. A acupuntura tanto no tratamento sistêmico, auricular e/ou emergencial, estabiliza os sintomas da HAS e auxilia na redução dos fatores de risco para o desenvolvimento de doenças cardiovasculares. O objetivo do estudo foi compreender a percepção de indivíduos hipertensos, atendidos em uma unidade de pronto atendimento sobre a acupuntura. Trata-se de uma pesquisa descritiva, qualitativa, realizada na cidade de Cascavel ­ PR. Os participantes da pesquisa responderam a seguinte questão norteadora: "O que o sr. (sra.) sabe a respeito da acupuntura?". Participaram do estudo 36 indivíduos, sendo a maioria do sexo feminino, idade média de 52,2 anos e a maior parte com Ensino Fundamental incompleto. Com relação ao conhecimento sobre a acupuntura, 61% dos participantes desconhecem a técnica. As respostas favoráveis corresponderam a 39% e foram agrupadas em categorias: técnica com agulhas; utilizada para o tratamento do estresse; conhecimento por meio da mídia; traz benefícios. Ao final do estudo conclui-se que a maior parte dos indivíduos abordados desconhece a técnica de acupuntura. Os que demonstram conhecimento se limitam nos benefícios e possibilidades da técnica. A divulgação da acupuntura e a sua implantação no Sistema Único de Saúde, colaborariam para que esta visão se ampliasse e mais pessoas dos mais variados níveis socioeconômicos tivessem acesso aos benefícios da técnica.

Systemic arterial hypertension (SAH) is a multifactorial clinical condition characterized by elevated and sustained blood pressure levels. Acupuncture in both systemic, auricular and/or emergency treatment stabilizes the symptoms of SAH and helps to reduce the risk factors for the development of cardiovascular diseases. The aim of the study was to understand the perception of hypertensive individuals attended at an Emergency Medical Unit about acupuncture. This is a descriptive, qualitative research carried out in the city of Cascavel, in the state of Paraná. The survey participants answered the following guiding question: "What do you know about acupuncture?". Thirty-six people took part in the study, most of them were female, average age of 52.2 years and the majority had an incomplete secondary education. In terms of their knowledge about acupuncture, 61% of the participants did not know the technique. The favorable answers corresponded to 39% and were grouped in categories: technique with needles; used for treating stress; knowledge through media; benefits. At the end of the study, it was concluded that most of the participants in the study were unaware of the acupuncture technique. Those who demonstrate knowledge showed that it was limited in the benefits and possibilities of the technique. The dissemination of acupuncture and its implantation in the Public Health System would collaborate so that these thoughts could be further developed, and more people of the most varied socioeconomic levels could have access to its benefits.

Quantitative Evaluation of Bleeding during Blood Vessel Puncture Caused by Fine Needle in Lower Abdomen.

Inserting a fine needle presents a trade-off problem between safety and accuracy. As one of the serious complications due to tissue damages during needle insertion, severe bleeding often occurs owing to blood vessel puncture. However, there are few researches to evaluate the safety quantitatively regarding bleeding during the fine needle insertion. Therefore, the purpose of this study was the quantitative evaluation of the amount of bleeding due the artery and vein puncture depending on the needle size. We developed a blood circulation system for measuring the amount of bleeding due to blood vessel puncture. Using the system, the amount of bleeding due to different needle sizes was evaluated. The results suggested that the amount of bleeding per unit time increased depending on the needle radius. According to ordinal safety standards, the 22-gauge needle is appropriate for insertion into the lower abdomen.

Comparison of 22G standard and Franseen needles in endoscopic ultrasound-guided fine-needle aspiration for diagnosing pancreatic mass lesions: Study protocol for a controlled trial.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was developed with the aim of further improving the diagnostic performance of endoscopic ultrasound. Although novel puncture needles have been specifically designed for collecting sufficient tissue specimens, clinical studies have indicated no clear difference in diagnostic performance between these novel needles and conventional puncture needles. Recently, a needle with Franseen geometry was developed specifically for EUS-FNA biopsy. Due to the characteristic shape of its tip, the Franseen needle is expected to be effective for scraping tissues, thus potentially increasing the diagnostic accuracy of EUS-FNA biopsy. We plan to carry out a prospective, multicenter, open-labeled, controlled trial to compare conventional and Franseen needles in terms of the diagnostic accuracy of EUS-FNA for evaluating the malignancy of pancreatic mass lesions. METHODS/DESIGN: The study will enroll 520 patients with pancreatic mass managed at any of 21 participating endoscopic centers. Lesion samples obtained using 22G conventional and Franseen needles will be assessed to compare the efficacy and safety of these two types of needles in EUS-FNA for evaluating the malignancy of mass lesions in the pancreas. Tissue samples will be fixed in formalin and processed for histologic evaluation. For the purpose of this study, only samples obtained with the first needle pass will be used for comparing the: (i) accuracy of the malignancy diagnosis, (ii) sensitivity and specificity for the malignancy diagnosis, (iii) procedure completion rate, (iv) sample cellularity, and (v) incidence of complications. Patient enrollment begins on July 17, 2018. DISCUSSION: The outcomes of this study may provide insight into the optimal needle choice for evaluating the malignancy of pancreatic solid lesions, thus aiding in the development of practice guidelines for pancreatic diseases. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000030634. Registered on 29 December 2017. http://www.umin.ac.jp/ Version number: 01.2017.12.28.

Medical Devices; General and Plastic Surgery Devices; Classification of the Microneedling Device for Aesthetic Use. Final order.

The Food and Drug Administration (FDA or we) is classifying the microneedling device for aesthetic use into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the microneedling device for aesthetic use's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Minimally-invasive, microneedle-array extraction of interstitial fluid for comprehensive biomedical applications: transcriptomics, proteomics, metabolomics, exosome research, and biomarker identification.

Interstitial fluid (ISF) has recently garnered interest as a biological fluid that could be used as an alternate to blood for biomedical applications, diagnosis, and therapy. ISF extraction techniques are promising because they are less invasive and less painful than venipuncture. ISF is an alternative, incompletely characterized source of physiological data. Here, we describe a novel method of ISF extraction in rats, using microneedle arrays, which provides volumes of ISF that are sufficient for downstream analysis techniques such as proteomics, genomics, and extracellular vesicle purification and analysis. This method is potentially less invasive than previously reported techniques. The limited invasiveness and larger volumes of extracted ISF afforded by this microneedle-assisted ISF extraction method provide a technique that is less stressful and more humane to laboratory animals, while also allowing for a reduction in the numbers of animals needed to acquire sufficient volumes of ISF for biomedical analysis and application.

EUS-guided reverse bevel fine-needle biopsy sampling and open tip fine-needle aspiration in solid pancreatic lesions - a prospective, comparative study.

OBJECTIVES: Different diagnostic entities can present as solid pancreatic lesions (SPL). This study aimed to explore the utility of endoscopic ultrasound-guided reverse bevel fine-needle biopsy sampling (EUS-FNB) in SPLs. MATERIAL AND METHODS: In 2012-2015, consecutive patients with SPLs were prospectively included in a tertiary center setting and subjected to dual needle sampling with a 22 gauge reverse bevel biopsy needle and a conventional 25 gauge open tip aspiration needle (EUS-FNA). The outcome measures were the diagnostic accuracy of sampling, calculated for each modality separately and for the modalities combined (EUS-FNA + FNB), and the adverse event rate related to sampling. RESULTS: In 68 unique study subjects, the most common diagnostic entities were pancreatic neuroendocrine tumor, PNET, (34%), pancreatic ductal adenocarcinoma, PDAC, (32%), pancreatitis (15%) and metastasis (6%). The overall diagnostic accuracy of EUS-FNB was not significantly different from that of EUS-FNA, (69% vs. 78%, p = .31). EUS-FNA + FNB, compared with EUS-FNA alone, had a higher sensitivity for tumors other than PDAC (89% vs. 69%, p = .02) but not for PDACs (95% vs. 85%, p = .5). No adverse event was recorded after the study dual-needle sampling procedures. CONCLUSIONS: Endoscopic ultrasound-guided tissue acquisition performed with a 22 gauge reverse bevel biopsy needle is safe but not superior to conventional fine-needle aspiration performed with a 25 gauge open tip needle in diagnosing solid pancreatic lesions. However, the performance of both these modalities may facilitate the diagnostic work-up in selected patients, such as cases suspicious for pancreatic neuroendocrine tumors and metastases. NCT02360839.

Comparison of 22-gauge standard fine needle versus core biopsy needle for endoscopic ultrasound-guided sampling of suspected pancreatic cancer: a randomized crossover trial.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is effective for tissue diagnosis of pancreatic mass. To improve diagnostic yield and drawbacks, 22-gauge (G) core biopsy (FNB) needle has been developed. This study aims to compare 22G FNA and FNB needles for EUS-guided sampling of suspected pancreatic cancer. METHODS: This is a randomized controlled crossover trial. A total of 60 patients with suspected unresectable pancreatic cancer referred for EUS-guided sampling were randomly assigned to two groups. Both groups had 22G FNA and FNB needles performed in a randomized order. The primary endpoint was the cytological, histological and overall diagnostic accuracy of pancreatic cancer. RESULTS: FNA and FNB needles reported similar level of diagnostic accuracy (FNA needle 95% vs. FNB needle 93.3%; p = .564), and it was not statistically different. However, cytological cellularity was significantly higher in the FNB needles compared to FNA needles (odds ratio 2.75, 95% confidence interval (CI)). There were no procedure-related complications in both needles. CONCLUSIONS: The diagnostic accuracy of EUS-guided sampling for pancreatic cancer using 22G FNA is comparable to FNB needles. The cytological quality of specimen is better in the FNB needle.

Microneedles in the clinic.

In general, there is a profound influence of reducing physical dimensions of particulates and devices on their physico-chemical and biological properties, and their performance. Reduction in the dimensions of hypodermic needle to micron-scale size has gained tremendous interest among researchers. Research efforts and publications investigating the design, development and applications of microneedles have exponentially increased in the recent years. Especially, microneedles have been widely studied and developed for cosmetic and therapeutic applications. Intense research efforts during the past decade have led to approval and commercialization of several microneedle based/assisted products for clinical use. Furthermore, numerous clinical trials aimed towards investigating the safety and efficacy of microneedle based systems are ongoing. The objective of this review is to provide an overview of completed and ongoing clinical studies performed using microneedle-based technologies for cosmetic, therapeutic and diagnostic applications. The review also provides a detailed overview of designs and applications of microneedle based devices that have been approved or are under clinical investigations. Clinical reports of microneedles for cosmetic applications including acne vulgaris, acne scars, skin rejuvenation and hair growth, and for therapeutic applications including influenza vaccination, polio vaccination, and diabetes are discussed in this review. Overall, this review-for the first time-provides a comprehensive overview of clinical efforts and outcome of microneedle based systems.

The cellularity yield of three different 22-gauge endoscopic ultrasound fine needle aspiration needles.

BACKGROUND: Endoscopic ultrasound (EUS) fine needle aspiration (FNA) is an integral part in the diagnosis of pancreatic, intestinal and extra-intestinal masses or lesions. There is no clear data on the superiority of the core biopsy needle over standard 22-gauge needles. The aim of this study is to prospectively compare the cellularity yield of three commonly used 22-gauge FNA needles available in the US market. METHODS: This is a prospective, randomized study comparing the cellularity yield of three commercially available EUS needles (two standard FNA needles and core biopsy needle). Two blinded pathologists evaluated the cytology specimens based on an already agreed upon cytology score. We included adult patients (18-80 years old) who presented to our endoscopy unit for FNA of pancreatic or extrapancreatic masses. RESULTS: 109 patients (57 F, 52 M) were recruited to the study, 88 lesions were pancreatic lesions. 39 patients were recruited in the EZ Shot 2™ group, 36 in the Procore® group and 34 in the Expect™ group. The average cellularity score and the mean number of passes (SD) were not different between the three needles; P = 0.91 and P = 0.16, respectively. There was no difference between the three needles in obtaining an onsite diagnosis (P = 0.627) and no difference in reported adverse events between the three groups. CONCLUSION: The cellularity yields, the mean number of passes and reported adverse events were similar in the three compared 22-gauge needles. Diagn. Cytopathol. 2017;45:426-432. © 2017 Wiley Periodicals, Inc.