title: Comparison of modified Kessler and Yotsumoto-Dona suture: a biomechanical study on porcine tendons.

text: There is a need for a strong suture technique that allows early active mobilisation after repair of flexor tendons, but the best method has not yet been found. The aim of this study was to compare the modified Kessler suture biomechanically with a newer, two-strand suture. Eighteen porcine tendons were cut and repaired according to either the grasping modified Kessler suture or the combined side-locking loop technique (Yotsumoto) and interlocking horizontal mattress suture (Dona). The specimens were tested linearly to failure. The 2 mm gap force, yield force, ultimate force, stiffness, energy to yield, and energy to failure were all significantly higher (p value = 0.005, 0.003, <0.001, 0.001, 0.004, and 0.001, respectively) in the Yotsumoto-Dona group (median values (IQR): 30.9 (28.1-39.5) N, 82.7 (64.9-114.1) N, 82.7 (76.6-114.1) N, 12.5 (10-14.5) N/mm, 0.45 (0.2-0.5) J, and 0.45 (0.35-0.5) J) than in the modified Kessler group (25.8 (12.2-28.1) N, 35 (24.6-54.4) N, 50.9 (34.4-55.1) N, 7 (5.8-91) N/mm, 0.09 (0.06-0.18) J, and 0.21 (0.18-0.28) J). All Yotsumoto-Dona specimens had a yield force exceeding 35 N, while in the Kessler group only four did. The early yielding rate was 6/9 and 2/9 in the modified Kessler and the Yotsumoto-Dona groups, respectively (p = 0.15). Most of the core sutures failed by breakage, but three Yotsumoto knots loosened. All the simple running and six of the Dona epitendinous sutures failed predominantly by pulling-out, and by breakage at the intersections in three of the latter. The relatively easy two-strand Yotsumoto-Dona suture is likely to withstand the loads of active finger flexion, whereas the modified Kessler suture is probably not.


title: Laboratory Parameters in Detection of COVID-19 Patients with Positive RT-PCR; a Diagnostic Accuracy Study.

text: Introduction The role of laboratory parameters in screening of COVID-19 cases has not been definitely established. This study aimed to evaluate the accuracy of laboratory parameters in predicting cases with positive RT-PCR for COVID-19. Methods This diagnostic accuracy study was conducted on suspected COVID-19 patients, who presented to Behpooyan Clinic Medical center in Tehran (Iran) from 22 February to 14 March, 2020. Patients were divided into two groups based on the results of real time reverse transcriptase-polymerase chain reaction (RT-PCR) for COVID-19, and the accuracy of different laboratory parameters in predicting cases with positive RT-PCR was evaluated using area under the ROC curve (AUC). Results Two hundred cases with the mean age of 41.3± 14.6 (range: 19-78) years were studied (0.53% male). The result of RT-PCR for COVID-19 was positive in 70 (35%) cases. Patients with positive RT-PCR had significantly higher neutrophil (NEU) count (p = 0.0001), and C-reactive protein (CRP) (p = 0.04), lactate dehydrogenase (LDH) (p = 0.0001), aspartate aminotransferase (AST) (p = 0.001), alanine aminotransferase (ALT) (p = 0.0001), and Urea (p = 0.001) levels in serum. In addition, patients with positive RT-PCR had lower white blood cell (WBC) count (p = 0.0001) and serum albumin level (p = 0.0001) compared to others. ALT (AUC = 0.879), CRP (AUC = 0.870), NEU (AUC = 0.858), LDH (AUC = 0.835), and Urea (AUC = 0.835) had very good accuracy in predicting cases with positive RT-PCR for COVID-19, respectively. Conclusion Our findings suggest that level of LDH, CRP, ALT and NEU can be used to predict the result of COVID-19 test. They can help in detection of COVID-19 patients.


title: [A Case of Rectal Cancer with Virchow Lymph Node Metastasis in Which Complete Response Was Achieved with Chemoradiation Therapy].

text: A 43-year-old man underwent a low anterior resection of the rectum due to upper rectal cancer. The pathological Stage was Ⅳ with para-aortic lymph node metastasis. Postoperative chemotherapy with CapeOX was initiated, but para-aortic lymph node metastasis was discovered 4months after the surgery. Chemoradiation therapy with Cape and Bev, and 70 Gy/28 Fr led to the disappearance of the metastasized lesions. At 13months after the surgery, FDG accumulation was observed in the Virchow's lymph node, and chemotherapy with IRIS and Bev was initially administered. Subsequently, chemoradiation therapy with S-1 and Bev, and 66 Gy/33Fr was administered, followed by chemotherapy with S-1 and Bev, S-1. These therapies led to complete response(CR). However, 35 months after the surgery, the Virchow's lymph node had enlarged again, and chemoradiation therapy with S-1 and 60 Gy/30Fr was administered. Although no FDG accumulation was detected in the lymph node at 40 months after the surgery, metastasis was found in the mediastinal lymph nodes. Panitumumab therapy achieved CR, and no metastasis had been identified at 60 months after the final therapy. Chemoradiation therapy is a treatment option to improve the prognosis of patients with metastasis only in the Virchow's lymph node.


title: [Human bocavirus in Chile: clinical characteristics and epidemiological profile in children with acute respiratory tract infections].

text: BACKGROUND Human bocavirus (HBoV) is a newly discovered parvovirus found in children with acute respiratory tract infections (ARTI). OBJECTIVES To describe the epidemiological and clinical profile of children < 5 years old consulting for ARTI, comparing cases of HBoV monoinfection and coinfection with other known respiratory viruses. Furthermore, we aimed to estimate the prevalence of viral shedding in asymptomatic children and perform phylogenetic analysis. PATIENTS AND METHODS We investigated the presence of HBoV in nasopharyngeal secretions from children consulting for AlRTI and among asymptomatic controls, between 2007 and 2008, by polymerase chain reaction. RESULTS HBoV was detected in 79 (21.8%) of 362 nasopharyngeal swabs obtained from children with ARTI. In 60/79 (76%), coinfection with other respiratory viruses was confirmed. Most common symptoms were cough, fever and rhinorrhea. Children infected only with HBoV showed significantly lower frequencies of respiratory distress, oxygen requirements and hospital admission than those with coinfection. HBoV was detected in 6/16 (37.5%) samples from asymptomatic children. The phylogenetic analysis of viruses from Chilean patients revealed that circulating HBoV was closely related to original strains. CONCLUSIONS HBoV was found either in symptomatic and asymptomatic children. The severity of the disease was greater when HBoV was associated to other respiratory viruses.


title: Update: Severe acute respiratory syndrome--United States, 2003.

text: CDC and the World Health Organization (WHO) are continuing to investigate the multicountry outbreak of severe acute respiratory syndrome (SARS). This report updates information on reported SARS cases among U.S. residents and summarizes information on patients with no recent travel outside the United States.


title: Induction of milk IgA antibodies by porcine respiratory coronavirus infection.

text: An ELISA was developed to examine the prevalence of TGEV-specific immunoglobulin (Ig)A in the milk of sows, infected in the field with PRCV or with TGEV. It was shown that previous PRCV-infections can induce the secretion of IgA antibodies in the milk. However, only 9 out of 28 PRCV-infected sows had IgA in their milk whereas 11 TGEV-infected sows all secreted IgA. On farms where a reinfection with PRCV occurred, the number of IgA-secreting sows increased from 2 to 11 on a total of 13 sows. This showed that the presence of IgA antibodies in the milk may depend upon the occurrence of reinfection with PRCV. As demonstrated by density gradient analysis, the milk IgA induced by PRCV was 11S secretory IgA and had the capacity to neutralize TGEV.


title: Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV), a newly identified group 2 coronavirus, is the causative agent of severe acute respiratory syndrome, a life-threatening form of pneumonia in humans. Coronavirus replication and transcription are highly specialized processes of cytoplasmic RNA synthesis that localize to virus-induced membrane structures and were recently proposed to involve a complex enzymatic machinery that, besides RNA-dependent RNA polymerase, helicase, and protease activities, also involves a series of RNA-processing enzymes that are not found in most other RNA virus families. Here, we characterized the enzymatic activities of a recombinant form of the SARS-CoV helicase (nonstructural protein [nsp] 13), a superfamily 1 helicase with an N-terminal zinc-binding domain. We report that nsp13 has both RNA and DNA duplex-unwinding activities. SARS-CoV nsp13 unwinds its substrates in a 5'-to-3' direction and features a remarkable processivity, allowing efficient strand separation of extended regions of double-stranded RNA and DNA. Characterization of the nsp13-associated (deoxy)nucleoside triphosphatase ([dNTPase) activities revealed that all natural nucleotides and deoxynucleotides are substrates of nsp13, with ATP, dATP, and GTP being hydrolyzed slightly more efficiently than other nucleotides. Furthermore, we established an RNA 5'-triphosphatase activity for the SARS-CoV nsp13 helicase which may be involved in the formation of the 5' cap structure of viral RNAs. The data suggest that the (d)NTPase and RNA 5'-triphosphatase activities of nsp13 have a common active site. Finally, we established that, in SARS-CoV-infected Vero E6 cells, nsp13 localizes to membranes that appear to be derived from the endoplasmic reticulum and are the likely site of SARS-CoV RNA synthesis.


title: Reduction of carriage of enterohemorrhagic Escherichia coli O157:H7 in cattle by inoculation with probiotic bacteria.

text: Bacteria inhibitory to Escherichia coli O157:H7 were isolated from cattle and evaluated for their potential for reducing carriage of E. coli O157:H7 in calves. Eighteen of 1,200 bacterial isolates from cattle feces and intestinal tissue samples were screened and determined to inhibit the growth of E. coli O157:H7 in vitro. Seventeen of the isolates were E. coli and one was Proteus mirabilis. None produced Shiga toxin. Genomic DNA fingerprinting by pulsed-field gel electrophoresis revealed 13 distinguishable profiles among the 18 isolates. Two calves inoculated perorally with a mixture of all 18 isolates (10(10) CFU) appeared to be normal and did not develop signs of clinical disease throughout a 25- to 27-day observation period. These bacteria colonized segments of the gastrointestinal tract and were in feces at the termination of the experiment (25 and 27 days postinoculation) at levels of 50 to 200 CFU/g. Fifteen cannulated calves were studied to determine the efficiency of the probiotic bacteria in reducing or eliminating the carriage of E. coli O157:H7. Nine calves served as controls, with each animal receiving perorally 10(10) CFU of E. coli O157:H7. E. coli O157:H7 was detected intermittently in the rumen samples from all control animals throughout 3 weeks postinoculation, whereas E. coli O157:H7 was shed at various levels in feces continuously throughout the experiment (mean, 28 days). E. coli O157:H7 was isolated from the rumens and colons of eight of nine and nine of nine calves, respectively, at the termination of the study. Six calves each received perorally 10(10) CFU of probiotic bacteria and then 2 days later received 10(10) CFU of E. coli O157:H7. E. coli O157:H7 was detected in the rumen for only 9 days postinoculation in two animals, for 16 days in one animal, for 17 days in two animals, and for 29 days in one animal. E. coli O157:H7 was detected in feces for only 11 days postinoculation in one animal, for 15 days in one animal, for 17 days in one animal, for 18 days in one animal, for 19 days in one animal, and for 29 days in one animal. At the end of the experiment (mean, 30 days), E. coli O157:H7 was not recovered from the rumen of any of the six animals treated with probiotic bacteria; however, E. coli O157:H7 was recovered from the feces of one of the animals. This animal was fasted twice postinoculation. These studies indicate that selected probiotic bacteria administered to cattle prior to exposure to E. coli O157:H7 can reduce the level of carriage of E. coli O157:H7 in most animals.


title: Health-care provider preferences for time-sensitive communications from public health agencies.

text: OBJECTIVE The Rapid Emergency Alert Communication in Health (REACH) Trial was a randomized control trial to systematically compare and evaluate the effectiveness of traditional and mobile communication modalities for public health agencies to disseminate time-sensitive information to health-care providers (HCPs). We conducted a sub-study to identify the communication channels by which HCPs preferred receiving public health alerts and advisories. METHODS Enrolled HCPs were blindly randomized into four message delivery groups to receive time-sensitive public health messages by e-mail, fax, or short message service (SMS) or to a no-message control group. Follow-up interviews were conducted 5-10 days after the message. In the final interview, additional questions were asked regarding HCP preferences for receiving public health alerts and advisories. We examined the relationship between key covariates and preferred method of receiving public health alert and advisory messages. RESULTS Gender, age, provider type, and study site showed statistically significant associations with delivery method preference. Older providers were more likely than younger providers to prefer e-mail or fax, while younger providers were more likely than older providers to prefer receiving messages via SMS. CONCLUSIONS There is currently no evidence-based research to guide or improve communication between public health agencies and HCPs. Understanding the preferences of providers for receiving alerts and advisories may improve the effectiveness of vital public health communications systems and, in turn, may enhance disease surveillance, aid in early detection, and improve case finding and situational awareness for public health emergencies.


title: Continuous cerebral hemodynamic measurement during deep hypothermic circulatory arrest.

text: While survival of children with complex congenital heart defects has improved in recent years, roughly half suffer neurological deficits suspected to be related to cerebral ischemia. Here we report the first demonstration of optical diffuse correlation spectroscopy (DCS) for continuous and non-invasive monitoring of cerebral microvascular blood flow during complex human neonatal or cardiac surgery. Comparison between DCS and Doppler ultrasound flow measurements during deep hypothermia, circulatory arrest, and rewarming were in good agreement. Looking forward, DCS instrumentation, alone and with NIRS, could provide access to flow and metabolic biomarkers needed by clinicians to adjust neuroprotective therapy during surgery.


title: Drug overdose deaths--Florida, 2003-2009.

text: In the United States in 2007, unintentional poisonings were the second leading cause of injury death (after motor-vehicle crashes); approximately 93% of all unintentional poisoning deaths were caused by drug poisoning, also known as drug overdose. From 1990 to 2001 in Florida, the nonsuicidal poisoning death rate increased 325%. To characterize recent trends in drug overdose death rates in Florida, CDC analyzed data from the Florida Medical Examiners Commission. This report summarizes the results of that analysis, which found that, from 2003 to 2009, the number of annual deaths in which medical examiner testing showed lethal concentrations of one or more drugs increased 61.0%, from 1,804 to 2,905, and the death rate increased 47.5%, from 10.6 to 15.7 per 100,000 population. During 2003-2009, death rates increased for all substances except cocaine and heroin. The death rate for prescription drugs increased 84.2%, from 7.3 to 13.4 per 100,000 population. The greatest increase was observed in the death rate from oxycodone (264.6%), followed by alprazolam (233.8%) and methadone (79.2%). By 2009, the number of deaths involving prescription drugs was four times the number involving illicit drugs. These findings indicate the need to strengthen interventions aimed at reducing overdose deaths from prescription drugs in Florida. Medical examiner records are a timely, population-based source for data regarding overdose deaths from specific drugs. The data in this report and subsequent analyses can be used to design and measure the effectiveness of interventions.


title: Clinicopathology of severe acute respiratory syndrome: an autopsy case report.

text: In mid-April 2003, a major outbreak of severe acute respiratory syndrome (SARS) developed in Taiwan. During the outbreak, SARS-associated coronavirus (SARS-CoV) was documented in 346 patients and 73 of them died. Autopsy was performed in 9 of the suspected SARS patients who died during the outbreak, but SARS was the cause of death in only 1 of these patients. Here we report the histological features of this patient and their clinicopathological correlations. The patient, a 36-year-old Indonesian woman, was a caretaker working for a Taiwanese family. She stayed in Taipei Jen-Chi Hospital from April 10 to April 19 to take care of her elderly employer. She developed fever on April 21 and respiratory distress on April 25, and received ribavirin, intravenous immunoglobulin, and steroid. The respiratory distress persisted and worsened, and intubation was performed on April 27. The respiratory condition improved initially after mechanical ventilation, but subcutaneous emphysema and pneumomediastinum developed on May 1. Her condition deteriorated rapidly and she died on May 2, 11 days after the onset of fever. Autopsy was performed on the same day. Histologically, the lungs showed severe diffuse alveolar damage and bronchopneumonia, but no viral inclusion. The spleen and lymph nodes revealed lymphoid depletion and the liver showed microvesicular steatosis. No specific pathological change was seen in the gastrointestinal tract and kidneys. SARS-CoV genome was detected in the nasopharyngeal aspirate and the autopsy lung specimen.


title: Bypass Operation for Unresectable Esophageal Cancer: Postoperative Complications After Thoracotomy Versus No Thoracotomy.

text: Patients with unresectable esophageal cancer suffer from dysphagia, causing severe malnutrition and reduced quality of life (QOL). We elect to perform bypass because patients can have greater long-term survival with chemoradiation following this operation. We sought to compare complications in cases of bypass without thoracotomy versus those with thoracotomy. Thirty-four locally advanced esophageal cancer patients between 2007 and 2014 were studied. Eighteen patients underwent thoracotomy, and 16 patients did not have a thoracotomy. CT was obtained to check the anastomosis and the oral stump of the esophagus and to measure the diameter of the intrathoracic esophagus. In the thoracotomy group, the rate of postoperative pulmonary complications was high. On the other hand, in the non-thoracotomy group, the rates of anastomotic leak and recurrent nerve paralysis were high. The stump of the esophagus was 2 cm lower in the T group than in the nT group. As the esophagus shortens after division, the final difference in esophageal height between the groups was only around 1 cm. We concluded that a viable gastric tube with a good blood supply as well as a careful cervical operation are the most important aspects of the esophageal bypass operation.


title: DRAK2 regulates memory T cell responses following murine coronavirus infection.

text: The contribution of DRAK2 [death-associated protein kinase (DAPK)-related apoptosis-inducing kinase 2] to anti-viral memory T cell responses following infection with mouse hepatitis virus (MHV) was examined. DRAK2 is a lymphoid-enriched serine/threonine kinase that is an important regulatory molecule involved in modulating T cell responses. Memory T cells derived from MHV-immunized Drak2(-/-) mice exhibited amplified proliferation and IFN-gamma secretion following stimulation with viral epitopes. Transfer of Drak2(-/-) memory T cells into Rag1(-/-) mice infected intracerebrally with MHV resulted in accelerated clearance of virus from the brain. Thus, DRAK2 may be a novel target for stimulating protective immunity to viral pathogens.


title: The changing face of pediatric respiratory tract infections: how human metapneumovirus and human bocavirus fit into the overall etiology of respiratory tract infections in young children.

text: Lower respiratory tract infections are one of the leading causes of morbidity and mortality in children worldwide. Recent technological advances in the field of molecular biology have allowed virologists to detect many previously undetected viral pathogens. Two of these, human metapneumovirus (hMPV) and human bocavirus (HBoV), are of particular clinical interest to pediatric health care providers. This review discusses the most common viral respiratory infections in children, explores the role of newly discovered respiratory pathogens, and describes techniques for the diagnosis of viral respiratory infections.


title: Managing severe acute respiratory syndrome (SARS) intellectual property rights: the possible role of patent pooling.

text: Patent applications that incorporate the genomic sequence of the severe acute respiratory syndrome (SARS) coronavirus, have been filed by a number of organizations. This is likely to result in a fragmentation of intellectual property (IP) rights which in turn may adversely affect the development of products, such as vaccines, to combat SARS. Placing these patent rights into a patent pool to be licensed on a non-exclusive basis may circumvent these difficulties and set a key precedent for the use of this form of mechanism in other areas of health care, leading to benefits to public health.


title: Clarification of how HIV-1 DNA and protein immunizations may be better used to obtain HIV-1-specific mucosal and systemic immunity.

text: More focused research on a mucosal HIV-1 vaccine is needed urgently. An increasing amount of collected data, using heterologous multimodality prime-booster strategies, suggest that an efficient and protective HIV-1 vaccine must generate broad, long-lasting HIV-specific CD8(+) cytotoxic T-lymphocyte and neutralizing antibody responses. In the mucosa, these responses would be most effective if a preferential stimulus of HIV-1 neutralizing secretory immunoglobulin A and G were obtained. The attractive property of mucosal immunization is the obtained mucosal and systemic immunity, whereas systemic immunization induces a more limited immunity, predominantly in systemic sites. These objectives will require new vaccine regimens, such as multiclade HIV DNA and protein vaccines (nef, tat, gag and env expressed in DNA plasmids) delivered onto mucosal surfaces with needle-free delivery methods, such as nasal drop, as well as oral and rectal/vaginal delivery, and should merit clinical trials.


title: Efficient annotation of non-coding RNA structures including pseudoknots via automated filters.

text: Computational search of genomes for RNA secondary structure is an important approach to the annotation of non-coding RNAs. The bottleneck of the search is sequence-structure alignment, which is often computationally intensive. A plausible solution is to devise effective filters that can efficiently remove segments unlikely to contain the desired structure patterns in the genome and to apply search only on the remaining portions. Since filters can be substructures of the RNA to be searched, the strategy to select which substructures to use as filters is critical to the overall search speed up. Such an issue becomes more involved when the structure contains pseudoknots; approaches that can filter pseudoknots are yet available. In this paper, a new effective filtration scheme is introduced to filter RNA pseudoknots. Based upon the authors' earlier work in tree-decomposable graph model for RNA pseudoknots, the new scheme can automatically derive a set of filters with the overall optimal filtration ratio. Search experiments on both synthetic and biological genomes showed that, with this filtration approach, RNA structure search can speed up 11 to 60 folds while maintaining the same search sensitivity and specificity of without the filtration. In some cases, the filtration even improves the specificity that is already high.


Severe acute respiratory syndrome: lessons may be learnt from the outbreak of legionnaires' disease in Barrow in Furness.


title: Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus.

text: Nitric oxide (NO) is an important signaling molecule between cells which has been shown to have an inhibitory effect on some virus infections. The purpose of this study was to examine whether NO inhibits the replication cycle of the severe acute respiratory syndrome coronavirus (SARS CoV) in vitro. We found that an organic NO donor, S-nitroso-N-acetylpenicillamine, significantly inhibited the replication cycle of SARS CoV in a concentration-dependent manner. We also show here that NO inhibits viral protein and RNA synthesis. Furthermore, we demonstrate that NO generated by inducible nitric oxide synthase, an enzyme that produces NO, inhibits the SARS CoV replication cycle.


title: Antiviral activity of Veronica persica Poir. on herpes virus infection.

text: The lack of an effective anti-viral agent and the emergence of drug-resistant strains dictate a real need for discovery of novel therapies able to ameliorate viral infections. In this regards, medicinal plants and natural products offer safe and inexpensive platforms for discovery of efficient and novel anti-viral agents. We have investigated the potential anti-viral activities of Veronica persica Poir. as a medicinal plant against herpes simplex viruses (HSVs). In vitro screening of the ethanol plant extract against HSV-1 and HSV-2 infected Vero cells revealed the extract to show a dose-dependent inhibitory activity against both virus strains. After fractionation of the extract by a stepwise methanol gradient and evaluation of each fraction, the 80% methanol fraction displayed a pronounced inhibitory activity against the herpes viruses. The highest antiviral activity was observed when the Vero cells were treated with the extract both during and after infection by viruses. Moreover, the extract showed a prominent synergistic activity in combination with acyclovir anti-HSV therapy. Our findings revealed the potential of V. persica extract, especially its 80% methanol fraction, in inhibition of herpes simplex viral infections.


title: Immediate Continence Rates in RALRP: A Comparison of Three Techniques.

text: BACKGROUND AND OBJECTIVES Robot-assisted laparoscopic radical prostatectomy (RALRP) is said to provide excellent long-term continence. In this study, we compared the early incontinence outcomes of our patients, who had undergone no reconstruction, posterior reconstruction only, or total anatomic restoration and posterior reconstruction. METHODS We retrospectively analyzed the patients who underwent RALRP for localized prostate cancer by a single surgeon in our clinic from January 1, 2009-February 1, 2016. Continence was defined as no leakage or use of a safety pad for minimal leakage. The main outcome measure was continence at postoperative week 1 and months 1, 6, and 12. RESULTS Between 2009 and 2016, 239 patients underwent RALRP for localized prostate disease. Seventy-four patients underwent a standard approach (group 1), 88 had posterior reconstruction (group 2), and 77 had posterior reconstruction with total anatomic restoration (group 3). After 1 week, 24.3% of the patients in group 1 (18/74), 31.8% in group 2 (28/88), and 45.8% in group 3 (33/72) were continent (P = .02). One month after the surgery, continence rates for groups 1, 2, and 3 were 56.7, 67, and 75%, respectively (0.065). After 6 and 12 months, continence rates for groups 1, 2, and 3 were 72.9 and 87.8%, 81.8 and 89.7%, and 84.7 and 91.6%, respectively (P = .178 and .7484). CONCLUSION Anatomic restoration improves continence rates in the early period after RALRP. Even though other parameters were higher in the total restoration group, immediate continence (at 1 week) was significantly better.


title: Salivary gland cancer in patients younger than 30 years.

text: Previous research has shown that salivary gland tumors are rare in the young population. A clinical diagnosis has to be made very carefully because the proportion of malignancies is higher in children than in adults. We present a review of cases of malignant salivary gland carcinoma (SGC) in patients younger than 30 years of age. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) 17 Registry. A total of 763 patients younger than 30 years with carcinoma of a major salivary gland from 1973 to 2004 were identified within the SEER database. The most common salivary gland cancer was mucoepidermoid parotid gland carcinoma. The incidence of all major salivary gland carcinomas increased with increasing patient age. The 5-year relative survival rate for salivary gland carcinomas in our population was calculated according to the Kaplan-Meier analysis in each age group. Relative 5-year survival was 100% in the 1 patient younger than 1 year, 50.0% in the 1- to 4-year-old group; 87.2% among the 5- to 9-year-olds; 97.0% among the 10- to 14-year-olds; 95.0% among the 15- to 19-year-olds; 95.1% among the 20- to 24-year-olds; and 93.6% in the 25- to 29-year-old group. We found that SGC affects patients of all ages, even children in the first year of life. It is essential for physicians to detect salivary gland neoplasms promptly and to evaluate them thoroughly when they are found in children.


What are human rights?


Developing the "NUS Tummy Dummy", a low-cost simulator to teach medical students to perform the abdominal examination.


title: The effects of coronavirus on human nasal ciliated respiratory epithelium.

text: Human coronavirus (HCoV) accounts for 15-30% of common colds, but only one case report has described the effect of a coronavirus infection, that was asymptomatic, on human respiratory epithelium. The authors examined the effects of infection with HCoV on ciliary structure and function in healthy volunteers infected by intranasal inoculation with HCoV 229E. A further four volunteers were sham infected with ultraviolet-inactivated virus. Immediately before inoculation (day 0) and 3 days later (day 3), ciliated epithelium was obtained by brushing the inferior nasal turbinate. Ciliary beat frequency was determined and beat pattern analysed for evidence of dyskinesia (0=normal, 3=severely dyskinetic) using digital high-speed video photography. Ciliary ultrastructure was examined by transmission electron microscopy. Symptom diaries were kept for the duration of the study. All subjects inoculated with HCoV, including the three who did not develop symptoms of an upper respiratory tract infection, had disruption of their respiratory epithelium on day 3. Although there was no difference in the mean ciliary beat frequency between day 0 (11.3 Hz (95% confidence interval (CI): 8.6-14.0) and day 3 (9.4 Hz (95% CI 7.2-11.6)), there was a significant increase (p<0.05) in the ciliary dyskinesia score between day 0 (0.2 (95% CI 0-0.5)) and day 3 (1.1 (95% CI 0.5-1.7). In sham-infected subjects, no differences in epithelial integrity, or ciliary structure and function were found between day 0 and day 3. Inoculation of healthy volunteers with human coronavirus caused disruption of the ciliated epithelium and ciliary dyskinesia. This is likely to impair mucociliary clearance. Damage to the respiratory epithelium, due to human coronavirus infection, may occur without overt clinical symptoms.


title: Simulating public health response to a severe acute respiratory syndrome (SARS) event: a comprehensive and systematic approach to designing, implementing, and evaluating a tabletop exercise.

text: In response to recent public health threats and disasters, greater emphasis has been placed on the use of exercises and drills to improve individual performance and enhance capacity of the public health workforce. However, despite the increased application of these exercises, rigorous research regarding their appropriate development and relative effectiveness in improving public health preparedness is limited. The present study attempted to fill this void by presenting a detailed account of a comprehensive and integrated approach to developing, implementing, and evaluating a tabletop exercise designed to enhance emergency preparedness and response of public health workers. Following a comprehensive training systems model, a tabletop exercise was developed to simulate worker recognition and response to a Severe Acute Respiratory Syndrome event among public health workers in Arkansas. Forty-nine individuals participated in the tabletop exercise, including public health workers and their external partners. Results demonstrated the effectiveness of this tabletop exercise in increasing participants' competency-related knowledge and skills. The flexibility afforded by creating a standardized competency-based process can extend to other state and local health departments and provides evidence of the reciprocal relationship between research and practice needed to advance the areas of emergency preparedness training and workforce development initiatives in public health.


Definition of the cellular interactome of the highly pathogenic avian influenza H5N1 virus: identification of human cellular regulators of viral entry, assembly, and egress.


title: Coronavirus induced encephalomyelitis: an immunodominant CD4(+)-T cell site on the nucleocapsid protein contributes to protection.

text: In this communication we present clear evidence, that the N-protein of MHV-JHM contains immunodominant CD4+ T-cell sites. These sites were recognized by the immune system of virus infected Lewis rats. In previous investigations we have shown, that CD4+ T-cell lines with specificity for defined viral proteins can be selected from diseased Lewis rats and mediate protection, if transferred to otherwise lethally infected animals. To define regions of the N-protein, which are immunodominant for the T-cell response, we employed bacterially expressed N-protein and truncated subfragments of N as an antigen. We demonstrate, that T-cells from MHV-JHM infected, diseased Lewis rats recognized with high prevalence the carboxyterminal subfragment C4-N (95 aa) and to some extent the adjacent C3-N protein. The same results were obtained with T-cells derived from rats immunized with bacterially expressed N-protein or from animals vaccinated by a stable N-protein expressing vaccinia recombinant. Finally, transfer of CD4+ line T-cells to MHV-JHM infected rats specific for C4-N mediated protection against acute disease.


title: A model for the reallocation of recycling containers: application to the case of glass.

text: From both the social as well as the economic perspective, the recycling of household waste products is of growing importance. The recycling of glass in particular is one of the most successful as far as public collaboration is concerned, as well as due to the demand for recycled material on the part of glass manufacturers. This article presents a model for designing the first stage in the reverse logistics chain, i.e. the collection of material (in our case, applying the model to the collection of glass) directly from the consumer by means of containers. The aim of this model is to determine how to distribute the recycling containers in a specific region in the most efficient way possible, taking into account the economic and sociological characteristics of the population (level of education, number of catering establishments, etc.), while attempting to maximise the material collected and reducing the logistics costs. The model has been applied to the case of the Principality of Asturias, Spain, obtaining estimations that improve the performance of the system.


Expression of murine coronavirus genes 1 and 7 is sufficient for viral RNA synthesis.


title: MuSiC: a tool for multiple sequence alignment with constraints.

text: SUMMARY MuSiC is a web server to perform the constrained alignment of a set of sequences, such that the user-specified residues/nucleotides are aligned with each other. The input of the MuSiC system consists of a set of protein/DNA/RNA sequences and a set of user-specified constraints, each with a fragment of residue/nucleotide that (approximately) appears in all input sequences. The output of MuSiC is a constrained multiple sequence alignment in which the fragments of the input sequences whose residues/nucleotides exhibit a given degree of similarity to a constraint are aligned together. The current MuSiC system is implemented in Java language and can be accessed via a simple web interface. AVAILABILITY http://genome.life.nctu.edu.tw/MUSIC


title: Compounds Derived from Epigallocatechin-3-Gallate (EGCG) as a Novel Approach to the Prevention of Viral Infections.

text: Pathogenic viral infections pose major health risks to humans and livestock due to viral infection-associated illnesses such as chronic or acute inflammation in crucial organs and systems, malignant and benign lesions. These lead to large number of illnesses and deaths worldwide each year. Outbreaks of emerging lethal viruses, such as Ebola virus, severe acute respiratory syndrome (SARS) virus and Middle East respiratory syndrome (MERS) virus, could lead to epidemics or even pandemics if they are not effectively controlled. Current strategies to prevent viral entry into the human body are focused on cleansing the surface of the skin that covers hands and fingers. Surface protection and disinfection against microorganisms, including viruses, is performed by sanitization of the skin surface through hand washing with soap and water, surface disinfectants, and hand sanitizers, particularly alcohol-based hand sanitizers. However, concerns about the overall ineffectiveness, toxicity of certain ingredients of disinfectants, pollution of the environment, and the short duration of antimicrobial activity of alcohol have not been addressed, and the epidemiology of certain major viral infections are not correlated inversely with the current measures of viral prevention. In addition to a short duration on the skin surface, alcohol is ineffective against certain viruses such as norovirus, rabies virus, and polio virus. There is a need for a novel approach to protect humans and livestock from infections of pathogenic viruses that is broadly effective, long-lasting (persistent), non-toxic, and environment-friendly. A strong candidate is a group of unique compounds found in Camellia sinensis (tea plant): the green tea polyphenols, in particular epigallocatechin-3-gallate (EGCG) and its lipophilic derivatives. This review discussed the weaknesses of current hand sanitizers, gathered published results from many studies on the antiviral activities of EGCG and its lipophilic derivatives, and the potential use of these compounds as a novel strategy for disease prevention, especially against pathogenic viruses.


title: Microbiologic spectrum and susceptibility pattern of clinical isolates from the pediatric intensive care unit in a single medical center - 6 years' experience.

text: BACKGROUND AND PURPOSE Nosocomial infection contributes to the morbidity and mortality of patients in hospital. Timely microbiologic surveillance and assessment of antimicrobial resistance is important for dealing with nosocomial infections. This retrospective review was conducted to evaluate the microbiologic spectrum and susceptibility pattern in the pediatric intensive care unit from 2001 to 2006. METHODS The microbiologic data and antimicrobial susceptibility of all clinical isolates in the pediatric intensive care unit between 2001 and 2006 were reviewed. The incidence and distribution of nosocomial infections and the associated pathogens were also analyzed. RESULTS 1163 clinical isolates were analyzed. The frequencies of Gram-positive and Gram-negative bacteria were 30.4% and 56.2%, respectively. Staphylococcus aureus was the most common isolate among the Gram-positive organisms, while Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae were the 3 leading Gram-negative isolates. The proportion of methicillin-resistant S. aureus (MRSA) to all S. aureus was 65.2%. Six vancomycin-resistant enterococci were isolated in 2003. Extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae accounted for 20% of K. pneumoniae isolates since 2005. Carbapenem-resistant P. aeruginosa accounted for 34% of P. aeruginosa isolates. The nosocomial infection rate was not reduced after moving to a new hospital building in 2003. Urinary tract infection (30.2%) was the most common nosocomial infection, followed by bloodstream infection (26.5%) and lower respiratory tract infection (25.3%). CONCLUSIONS MRSA, carbapenem-resistant P. aeruginosa, and ESBL-producing K. pneumoniae were the major concerns in this study. Good hand hygiene and strict aseptic procedures remain the most important factors for infection control.


title: In vivo effects of coronavirus-specific T cell clones: DTH inducer cells prevent a lethal infection but do not inhibit virus replication.

text: A lethal infection by neurotropic JHM strain of mouse hepatitis virus was prevented by the local adoptive transfer of three virus-specific Lyt-1+2-, L3T4+ T cell clones. The transfer of Lyt-1+ T cells specific for an unrelated antigen (hen egg lysozyme) did not protect. Protection required I region compatibility between the T cells and the recipients, and was reversed either by irradiation of the cells before transfer or by pretreatment of the recipients with cyclophosphamide. Adoptive transfer prevented death due to JHM virus infection but did not result in altered antiviral immunoglobulin synthesis or the suppression of viral replication in the central nervous system (CNS). The data presented implicate a local DTH response in the protection of the host from lethal infection of the CNS by a neurotropic virus, but clearly imply that other antiviral effector mechanisms are necessary for the suppression of viral replication.


Severe acute respiratory syndrome and Toronto.


title: Pathogenicity of three isolates of porcine respiratory coronavirus in the USA.

text: The pathogenicity of three isolates of porcine respiratory coronavirus (AR310, LEPP and 1894) from the USA was assessed in specific pathogen-free pigs. Pigs inoculated with 1894 developed mild respiratory disease and pigs inoculated with AR310 and LEPP developed moderate respiratory disease from four to 10 days after they were inoculated, but all the pigs recovered fully by 14 days after inoculation. Gross and microscopic examination revealed mild (1894) to moderate (AR310 and LEPP) multifocal bronchointerstitial pneumonia from four to 10 days after inoculation. The lesions were characterised by necrotising bronchiolitis, septal infiltration with mononuclear cells, and a mixed alveolar exudate. No clinical signs or microscopic lesions were observed in control pigs that had not been inoculated.


title: The respiratory presentation of severe combined immunodeficiency in two Mennonite children at a tertiary centre highlighting the importance of recognizing this pediatric emergency.

text: Severe combined immunodeficiency (SCID) is considered to be a pediatric emergency, with respiratory distress being the most common presenting symptom. The authors present two cases of SCID in children <4 months of age with respiratory distress at a tertiary care centre due to a recently described homozygous CD3 delta mutation found only in the Mexican Mennonite population. Failure to respond to broad-spectrum antibiotics prompted investigation for possible SCID. Bronchial alveolar lavage fluid from both patients grew Pneumocystis jiroveci, and flow cytometry revealed absent T cells. The CD3 delta gene is believed to be important in T cell differentiation and maturation. The present article reminds pediatricians and pediatric respirologists that the key to diagnosing SCID is to have a high index of suspicion if there is poor response to conventional therapies.


title: Comparing the effects of rise time and inspiratory cycling criteria on 6 different mechanical ventilators.

text: BACKGROUND Inspiratory rise time and cycling criteria are important settings in pressure support ventilation. The purpose of this study was to investigate the impact of minimum and maximum rise time and inspiratory cycling criteria settings on 6 new generation ventilators. Our hypothesis was there would be a difference in the exhaled tidal volume, inspiratory time, and peak flow among 6 different ventilators, based, on change in rise time and cycling criteria. METHODS The research utilized a breathing simulator and 4 different ventilator models. All mechanical ventilators were set to a spontaneous mode of ventilation with settings of pressure support 8 cm H2O and PEEP of 5 cm H2O. A minimum and maximum setting for rise time and cycling criteria were examined. Exhaled tidal volume, inspiratory time, and peak flow measurements were recorded for each simulation. RESULTS Significant (P < .001) differences were found when comparing minimum and maximum rise time and minimum and maximum cycling criteria for each ventilator. CONCLUSIONS Significant differences in exhaled tidal volume, inspiratory time, and peak flow were observed by adjusting rise time and cycling criteria. This research demonstrates that during pressure support ventilation strategy, adjustments in rise time and/or cycling criteria can produce changes in inspiratory parameters. Obviously, this finding has important implications for practitioners who utilize a similar pressure support strategy when conducting a ventilator wean. Additionally, this study outlines major differences among ventilator manufacturers when considering inspiratory rise time and cycling criteria.


title: A follow-up study of 69 discharged SARS patients.

text: Sixty-nine patients with severe acute respiratory syndrome (SARS) discharged from Guangdong Provincial TCM Hospital were followed up from January to April 2003 during which the patients were asked to fill the questionnaire form and at the same time received blood routine examination, hepatic, renal, pulmonary and immune function tests, and spiral computerized tomography (CT) of the chest, color B-ultrasonography of the heart with the collected data treated by descriptive analysis and deductive analysis. The results showed that in the 69 followed-up patients, impairment of the hepatic function was found in 5 cases, hypoimmune state in 18, impediment of ventilation in the distal air passages with normal major air passages in 15, increased residual volume in 40, mild disturbance of pulmonary diffusion function in 14, incomplete absorption of inflammatory exudates, focal or multiple interstitial lesions, pulmonary interstitial fibrosis and pleural adhesion in 24; increased resistance or mild systolic hypertension in the pulmonary circulation, and segmental ischemia of the left myocardium in 34; and decreased visual acuity in 2. According to TCM differentiation 24 cases belonged to the type of deficiency of both qi and yin, 8 deficiency of both the heart and spleen, 37 depression of the liver and deficiency of the spleen, 18 intermingling with damp-heat, and 7 intermingling with stagnant blood. Some patients still had psychological problems. The study indicates that though clinically cured and discharged from hospital, some SARS patients have functional impairment of the heart, lung and liver, hypoimmune state as well as psychological problems, and need to be treated accordingly for a complete recovery. A rationale for suggested TCM treatment is expounded.


Interfacing between primary and secondary care is needed.


title: The genome of human coronavirus strain 229E.

text: The genomic RNA of human coronavirus strain 229E (HCV 229E) migrated on polyacrylamide gels as a single peak with a mol. wt. of 5.8 X 10(6). Denaturation of the genome with formaldehyde did not alter its electrophoretic mobility, which suggests that the HCV 229E genome is a single-stranded molecule. At least 30% of the genomic RNA was shown to contain covalently attached polyadenylic acid [poly(A)]sequences by binding the RNA to an oligo(dT)-cellulose column. These poly(A) tracts were shown to be about 70 nucleotides in length by measuring the resistance to digestion of HCV 229E RNA with pancreatic and T1 RNases. Finally, the genomic RNA was shown to terminate at or near the 3'-terminus on the basis of its susceptibility to polynucleotide phosphorylase.


title: Single-Incision Laparoscopic Cholecystectomy: our experience and review of literature.

text: AIM After the revolution in the surgery of gallbladder stones represented by the laparoscopic cholecystectomy, we tried a new technique that further maximize the aesthetic results and that at the same time is of easy learning for young surgeons. PATIENTS AND METHODS From January 2011 to December 2012 we performed at our department 320 cholecystectomy: 27 in laparotomy and 293 in laparoscopy. Of these, 88 underwent to Single Incision Laparoscopic Surgery (SILS), namely the Single Incision Laparoscopic Cholecystectomy (SILC), in recruited patients aged between 19-65 years; 56 patients were females and 32 were males. RESULTS The laparoscopic cholecystectomy with the SILS methodology is a safe technique. Respect to multi-port Laparoscopic Cholecystectomy (LC), we have cosmetic advances. The pain is less in extraumbilical sites, and the major umbilical pain can be prevented by local anaesthesia. The times are slightly longer, especially at the beginning of training, but after a few of operations it is reduced to about one hour. We didn't found any other difference in vantage and advantage between the two technics, only a case of postoperative umbilical hernia in SILS. CONCLUSION We found the SILS a safe and effective technique for the cholecystectomy.


title: Enhanced suppression of adrenocorticotropic hormone and cortisol responses to hypothalamic-pituitary-adrenal function and thyrotropin-releasing hormone tests after stressful life events in patients with major depressive disorder.

text: BACKGROUND It is commonly believed that there exists a relationship between the outcome of thyrotropin-releasing hormone (TRH) test, the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) test and stressful life events (SLEs) in major depressive disorder. OBJECTIVE SLEs influence the TRH and DEX/CRH tests in major depressive disorder when administered at the time of admission and improvement. METHODS The TRH and DEX/CRH tests were administered to patients hospitalized for major depressive disorders - on the 4th through the 7th hospital day and at the time of improvement. We measured DeltaMAX TSH, DeltaMAX ACTH, ACTH AUC, DeltaMAX cortisol, cortisol AUC, DeltaMAX ACTH/DeltaMAX TSH and DeltaMAX cortisol/DeltaMAX TSH. RESULTS SLEs were significantly negatively associated with DeltaMAX ACTH, ACTH AUC and cortisol AUC at the time of admission. However, these relationships lost significance at the time of improvement. The sample (41 patients at the time of admission, 18 patients at the time of improvement) was relatively small, which may have contributed to false-negative results. CONCLUSION SLEs may be negatively associated with the outcome of the DEX/CRH tests in major depressive disorder. The hypothalamic-pituitary-adrenal axis in the DEX/CRH test was modulated by SLEs.


title: Detection of proteolytic activity by fluorescent zymogram in-gel assays.

text: Proteases are involved in the regulation of many biological functions. This study describes a novel method for detecting protease activity by fluorescent zymogram in-gel protease assays, using SDS polyacrylamide gels copolymerized with a peptide-MCA (4-methyl-coumaryl-7-amide) substrate. This method allows simultaneous determination of protease cleavage specificity and molecular weight. Trypsin was electrophoresed in SDS polyacrylamide gels copolymerized with Boc-Gln-Ala-Arg-MCA, the gel was then incubated in assay buffer, and trypsin cleavage of the peptide-MCA substrate generated fluorescent AMC (7-amino-4-methyl-coumarin), which was subsequently detected under UV transillumination. Chymotrypsin activity was detected in gels copolymerized with Suc-Ala-Ala-Pro-Phe-MCA substrate. Selective detection of these proteases was demonstrated by the absence of trypsin activity in gels containing the chymotrypsin substrate, and the lack of chymotrypsin activity in gels containing the trypsin substrate. Detection of proteolytic activity from secretory vesicles of adrenal medulla (chromaffin granules) was observed with the trypsin substrate, Z-Phe-Arg-MCA, but not with the chymotrypsin substrate. Overall, this sensitive fluorescent zymogram in-gel protease assay method can be used for rapid determination of protease cleavage specificity and enzyme molecular weight in biological samples. This assay should be useful for many research disciplines investigating the role of the many proteases that control cellular functions.


A contemporary view of coronavirus transcription.


Treating severe acute respiratory syndrome with hyperimmune globulins.


title: Spike protein of SARS-CoV stimulates cyclooxygenase-2 expression via both calcium-dependent and calcium-independent protein kinase C pathways.

text: We have previously shown that the nucleocapsid protein of SARS-associated coronavirus (SARS-CoV) activated cyclooxygenase-2 (COX-2) expression. In this study, we identified another viral protein, the spike of SARS-CoV, which played an important role in virus-stimulated COX-2 expression after screening all genes from the SARS-CoV genome. We found that an upstream calcium-dependent PKC isozyme PKC alpha that modulates the downstream ERK/NF-kappaB pathway through an influx of extracellular Ca2+ is induced by the spike protein of SARS-CoV. The ERK/NF-kappaB was identified to be involved in the activation of COX-2 promoter and production of COX-2 protein in HEK293T cells. We also demonstrated that another unusual pathway, the calcium-independent PI3K/PKC epsilon/JNK/CREB pathway, functioned in cooperation with the calcium-dependent pathway to induce COX-2 expression upon stimulation by spike protein. This pathway can be blocked by PKC epsilon-specific, small interfering RNA, PI3K/JNK kinase-specific inhibitors as well as dominant negative JNK. PKC epsilon-specific siRNA also attenuated the phosphorylation of JNK. Our results provide evidence that helps us understand the function of SRAS-CoV spike protein in SARS pathogenesis.


title: Strong antiviral activity of heated and hydrated dolomite--preliminary investigation.

text: Heated and hydrated naturally occurring dolomite showed very strong antiviral activity. Infectivity of avian and human influenza, avian infectious bronchitis (coronavirus), Newcastle disease (paramyxovirus) and avian laryngotracheitis (herpesvirus) viruses dropped at least 1,000 fold following contact with the dolomite for five minutes at 4 degrees C. Dolomite is expected to be useful to inhibit the incidence of emerging and re-emerging infectious diseases.


title: Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets.

text: Severe acute respiratory syndrome (SARS) caused by a newly identified coronavirus (SARS-CoV) is a serious emerging human infectious disease. In this report, we immunized ferrets (Mustela putorius furo) with recombinant modified vaccinia virus Ankara (rMVA) expressing the SARS-CoV spike (S) protein. Immunized ferrets developed a more rapid and vigorous neutralizing antibody response than control animals after challenge with SARS-CoV; however, they also exhibited strong inflammatory responses in liver tissue. Inflammation in control animals exposed to SARS-CoV was relatively mild. Thus, our data suggest that vaccination with rMVA expressing SARS-CoV S protein is associated with enhanced hepatitis.


title: [Viral nosocomial infections: the problem of contemporary hospital management].

text: The most frequent viral pathogens which are the cause of nosocomial infections were presented. Influenza and parainfluenza viruses as well as RS virus affect frequently respiratory tract. So called enteric viruses which are rotaviruses, adenoviruses, small round viruses, astroviruses, caliciviruses, corona viruses, Coxackie, ECHO may be the agents of disorders in digestive tract in the form of intoxications. Viruses of viral hepatitis B, C, D and HIV, CMV, EBV may be the source of nosocomial viral infections transmitted by blood (transfusions).


title: A Resampling-Based Test to Detect Person-To-Person Transmission of Infectious Disease.

text: Early detection of person-to-person transmission of emerging infectious diseases such as avian influenza is crucial for containing pandemics. We developed a simple permutation test and its refined version for this purpose. A simulation study shows that the refined permutation test is as powerful as or outcompetes the conventional test built on asymptotic theory, especially when the sample size is small. In addition, our resampling methods can be applied to a broad range of problems where an asymptotic test is not available or fails. We also found that decent statistical power could be attained with just a small number of cases, if the disease is moderately transmissible between humans.


Learning from SARS in Hong Kong and Toronto.


title: A rapid and potent DNA vaccination strategy defined by in vivo monitoring of antigen expression.

text: Induction of immunity after DNA vaccination is generally considered a slow process. Here we show that DNA delivery to the skin results in a highly transient pulse of antigen expression. Based on this information, we developed a new rapid and potent intradermal DNA vaccination method. By short-interval intradermal DNA delivery, robust T-cell responses, of a magnitude sufficient to reject established subcutaneous tumors, are generated within 12 d. Moreover, this vaccination strategy confers protecting humoral immunity against influenza A infection within 2 weeks after the start of vaccination. The strength and speed of this newly developed strategy will be beneficial in situations in which immunity is required in the shortest possible time.


title: COVID-19 from the perspective of an immunologist.

text: COVID-19 is an infectious disease caused by a coronavirus SARS-CoV-2. COVID-19 has a number of similarities to SARS and MERS diseases. Its highly contagious nature is particularly due to the rapid spread of the disease through asymptomatic individuals; however, the worlds most contagious infectious disease is still considered measles. Scientific data have revealed the interactions between COVID-19 and the immune system. These findings may contribute to the development of novel preventive and therapeutic approaches. Just as coronavirus itself the reports about the disease have massively spread through media and public contributing to overall public fear and stress. This promotion of non-scientific evidence and misinformation through social media might have also a devastating impact on the individuals immune system. Data regarding the mortality rates of COVID-19 have achieved unprecedented media and public engagements, however, the true facts about the disease prevention, immunomodulation and novel treatments are often left unsaid. We present the most recent facts about COVID-19 disease and its interactions with the immune system.


title: Role of recent vaccination in production of false-positive coronavirus antibody titers in cats.

text: Statistical support was obtained for an association between recent vaccination of cats and the presence of elevated background (i.e., anti-cell culture) reactivity in certain of their sera, as detected with a kinetics-based enzyme-linked immunosorbent assay for coronavirus antibodies, implicating routine vaccination as a potential cause of false-positive antibody test results.


title: Prevalence of four enteropathogens in the faeces of young diarrhoeic dairy calves in Switzerland.

text: The prevalences of Cryptosporidium parvum, rotavirus, bovine coronavirus (BCV), and enterotoxigenic Escherichia coli (E coli K99) were determined in diarrhoeic dairy calves aged one to 21 days on 71 dairy farms in western Switzerland during the winter of 2005 to 2006. Faecal samples from 147 untreated calves suffering from acute diarrhoea were analysed by standardised diagnostic methods, and the immunoglobulin status of each calf was evaluated. The prevalences of C parvum, rotavirus, BCV and E coli k99 were 55.0 per cent, 58.7 per cent, 7.8 per cent and 5.5 per cent, respectively. The proportions of herds positive for the respective pathogens among the herds with diarrhoeic calves were 41.7 per cent, 52.1 per cent, 2.1 per cent and 2.1 per cent. The immunoglobulin concentration in the serum of 90.5 per cent of the diarrhoeic calves was below 8 g/l.


title: Isolation and characterization of murine coronavirus mutants resistant to neutralization by soluble receptors.

text: Murine coronavirus mutants resistant to neutralization with soluble receptors were isolated to study the receptor-binding site on the S proteins since such mutants were expected to have mutations in an important site for receptor-binding. We have isolated five soluble receptor-resistant (srr) mutants which had mutations of a single amino acid at 3 different positions in S protein. Srr mutant 11 with an amino acid change at position 65 (Leu to His) in the S1 subunit showed an extremely reduced binding by virus overlay protein blot assay. However srr mutants with a mutation at 1114 (Leu to Phe) (srr mutants 3, 4 and 7) or 1163 (Cys to Phe) (srr mutant 18) in the S2 subunit had receptor-binding activity similar to that of wild type cl-2. These results suggest that an amino acid at position 62 located in a conserved region among MHV strains is in particular important for receptor binding. We also discuss why srr mutants with a mutation in S2 showed high resistance to neutralization by soluble receptor, irrespective of their binding to MHV receptors.


title: Detection of neonatal calf diarrhea virus, infant reovirus-like diarrhea virus, and a coronavirus using the fluorescent virus precipitin test.

text: Thirty-four calf and five infant fecal specimens were tested for the neonatal calf diarrhea virus (NCDV) and for the reovirus-like infantile diarrhea agent; respectively. The procedures used were the fluorescent virus precipitin test and immune electron microscopy. Fourteen of the calf stools contained detectable NCDV, and four of the five infant stools contained the reovirus-like human agent. Infectious NCDV was detected in four of the 34 calf fecal specimens when Madin-Darby bovine kidney cell cultures that had been inoculated with supernatant fluids from stool suspensions were stained with fluorescent antibody. The 20 calf stools that did not have detectable virus were examined for the bovine corona diarrhea virus. Coronavirus was found in two of these specimens.


title: Metabolic syndrome and inflammation markers in patients with schizophrenia and recurrent depressive disorder.

text: BACKGROUND The high prevalence of metabolic syndrome in patients with psychiatric disorders, almost double the prevalence reported for the general population, is worrying. The aim of this study is to investigate the presence of metabolic syndrome and inflammatory marker levels in patients with schizophrenia and recurrent depressive disorder in a Croatian psychiatric sample. SUBJECTS AND METHODS This study included 62 inpatients with schizophrenia and 62 with recurrent depressive disorder treated at the Department of Psychiatry, University Hospital Centre Split, enrolled from November 2011 until May 2012. The cases were compared to 124 healthy subjects from the general population. RESULTS The presence of metabolic syndrome was found in 56.5% of the patients with schizophrenia and 53.2% of the patients with depression, which was significantly more prevalent than in the control group (32.3%). The levels of inflammation markers (i.e., C-reactive protein and PAI-1) were significantly higher among patients with metabolic syndrome. CONCLUSIONS Patients with schizophrenia and recurrent depressive disorder demonstrate a high prevalence of metabolic syndrome that is also related to inflammation processes. In the context of integrative medicine, clinicians and researchers should consider psychiatric patients within a holistic approach.


title: A novel sorting signal for intracellular localization is present in the S protein of a porcine coronavirus but absent from severe acute respiratory syndrome-associated coronavirus.

text: Coronaviruses (CoV) mature by a budding process at intracellular membranes. Here we showed that the major surface protein S of a porcine CoV (transmissible gastroenteritis virus) is not transported to the cell surface but is retained intracellularly. Site-directed mutagenesis indicated that a tyrosine-dependent signal (YXXI) in the cytoplasmic tail is essential for intracellular localization of the S protein. Surface expression of mutant proteins was evident by immunofluorescence analysis and surface biotinylation. Intracellularly retained S proteins only contained endoglycosidase H-sensitive N-glycans, whereas mutant proteins that migrated to the plasma membrane acquired N-linked oligosaccharides of the complex type. Corresponding tyrosine residues are present in the cytoplasmic tails of the S proteins of other animal CoV but not in the tail portion of the S protein of severe acute respiratory syndrome (SARS)-CoV. Changing the SEPV tetrapeptide in the cytoplasmic tail to YEPI resulted in intracellular retention of the S protein of SARS-CoV. As the S proteins of CoV have receptor binding and fusion activities and are the main target of neutralizing antibodies, the differences in the transport behavior of the S proteins suggest different strategies in the virus host interactions between SARS-CoV and other coronaviruses.


title: Climate change impacts and risks for animal health in Asia.

text: The threat of climate change and global warming is now recognised worldwide and some alarming manifestations of change have occurred. The Asian continent, because of its size and diversity, may be affected significantly by the consequences of climate change, and its new status as a 'hub' of livestock production gives it an important role in mitigating possible impacts of climate variability on animal health. Animal health may be affected by climate change in four ways: heat-related diseases and stress, extreme weather events, adaptation of animal production systems to new environments, and emergence or re-emergence of infectious diseases, especially vector-borne diseases critically dependent on environmental and climatic conditions. To face these new menaces, the need for strong and efficient Veterinary Services is irrefutable, combined with good coordination of public health services, as many emerging human diseases are zoonoses. Asian developing countries have acute weaknesses in their Veterinary Services, which jeopardises the global surveillance network essential for early detection of hazards. Indeed, international cooperation within and outside Asia is vital to mitigating the risks of climate change to animal health in Asia.


title: Liver Resection or Resection Plus Intraoperative Echo-Guided Ablation in the Treatment of Colorectal Metastases: We Are Evaluating Their Effect for Cure.

text: This study determines the oncologic outcome of the combined resection and ablation strategy for colorectal liver metastases. Between January 1994 and December 2015, 373 patients underwent surgery for colorectal liver metastases. There were 284 patients who underwent hepatic resection only (Group 1) and 83 hepatic resection plus ablation (Group 2). Group 2 patients had a higher incidence of multiple metastases (100% in Group 2 vs 28.2% in Group 1; P < 0.001) and bilobar involvement (76.5% in Group 2 vs 12.9% in Group 1; P < 0.001) than Group 1 cases. Perioperative mortality was nil in either group, with a higher postoperative complication rate among Group 1 versus Group 2 cases (18 vs 0, respectively). The median follow-up was 90 months (range, 1-180), with a five-year overall survival for Group 1 and Group 2 of 51 per cent and 80 per cent, respectively (P = 0.193). Mean disease-free survival for patients with R0 resection was 55 per cent, 40 per cent, and 37 per cent at one, two, and three years, respectively, and remained steadily higher (at 50%) in those patients treated with resection combined with ablation up to five years (P = 0.069). The only intraoperative ablation failure was for a large lesion (≥5 cm). Our data support the use of intraoperative ablation when complete hepatic resection cannot be achieved.


title: Assessment of celecoxib poly(lactic-co-glycolic) acid nanoformulation on drug pharmacodynamics and pharmacokinetics in rats.

text: OBJECTIVE Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP). MATERIALS AND METHODS Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP). Plasma and urine (over 12 hrs) samples were collected prior to and post-treatment. The mean percent change from baseline of urine flow rate along with electrolyte concentrations in plasma and urine were assessed based on 100 g body weight. Using tissues collected 24 hrs post-treatment, gastrointestinal inflammation was estimated through duodenal and gastric prostaglandin E2 (PGE2) and duodenal myeloperoxidase (MPO) levels; while kidney tissue was examined for dilatation and necrosis. CEL concentration was assayed in renal tissue and plasma utilizing high-performance liquid chromatography. RESULTS Although there were significant changes when comparing CEL and CEL-NP to VEH in plasma sodium concentration and potassium excretion rate, there was no significant variation between CEL and CEL-NP. There was a significant reduction of protective duodenal PGE2 in CEL compared to VEH (p = 0.0088) and CEL-NP (p = 0.02). In the CEL-NP formulation, t1/2, Cmax, AUC0-∞, and Vd/F increased significantly when compared to CEL. CONCLUSIONS At the observed dosage and duration, CEL-NP may not affect CEL-associated electrolyte parameters in either plasma or urine; however, it does provide increased systemic exposure while potentially alleviating some gastrointestinal outcomes related to inflammation.


title: Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry.

text: Severe acute respiratory syndrome (SARS) is caused by an emergent coronavirus (SARS-CoV), for which there is currently no effective treatment. SARS-CoV mediates receptor binding and entry by its spike (S) glycoprotein, and infection is sensitive to lysosomotropic agents that perturb endosomal pH. We demonstrate here that the lysosomotropic-agent-mediated block to SARS-CoV infection is overcome by protease treatment of target-cell-associated virus. In addition, SARS-CoV infection was blocked by specific inhibitors of the pH-sensitive endosomal protease cathepsin L. A cell-free membrane-fusion system demonstrates that engagement of receptor followed by proteolysis is required for SARS-CoV membrane fusion and indicates that cathepsin L is sufficient to activate membrane fusion by SARS-CoV S. These results suggest that SARS-CoV infection results from a unique, three-step process: receptor binding and induced conformational changes in S glycoprotein followed by cathepsin L proteolysis within endosomes. The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection.


The Krever Commission--10 years later.


Note from the editors: MERS-CoV - the quest for the reservoir continues.


title: [The clinical characteristics and staging of severe acute respiratory syndrome].

text: OBJECTIVE To investigate the clinical characteristics and to initiate a clinical staging of severe acute respiratory syndrome (SARS). METHODS Retrospective analysis was conducted in the clinical symptoms, physical signs and the results of laboratory examinations from 1170 cases with SARS in Beijing, and the clinical characteristics in different stages of the disease were compared. RESULTS The initial symptom of SARS was pyrexia and the temperature was > 38 degrees C. The natural course of fever was about 14 days. In almost all cases, the respiratory symptoms and systemic toxic manifestations were observed. They came to a climax at the second week and then decreased or nearly disappeared after the third week. The physical signs of SARS were not obvious. The moist rales were observed in 43.3% of patients. Hypoxemia was a common characteristic in SARS. The decrease in partial pressure of oxygen in artery and oxygen saturation in pulse oximeter with normal partial pressure of carbon dioxide was found in most patients at the second week. Abnormal chest X-ray including infiltration and consolidation shadows were seen in 100% of patients. The abnormal images could be found at the first day, enlarged during the second week (to a climax at the 8th or 9th day), and then recovered from the 2 week. The amounts of CD(4)(+), CD(8)(+), and CD(3)(+) of peripheral blood were decreased at the early stage and recovered after 2 or 3 weeks. Some patients suffered from temporary multiple organ dysfunctions (mainly impairments of liver and myocardium). CONCLUSION The main clinical manifestations of SARS included respiratory and systemic toxic symptoms. The typical course of the disease was about 4 weeks. The first week could be considered as early stage, the second week as fastigium stage, and from the next two weeks as recovery stage.


title: Effect of chicken antibodies on inflammation in human lung epithelial cell lines.

text: OBJECTIVES As an alternative therapeutic approach for the prevention and treatment of bacterial infections with P. aeruginosa of cystic fibrosis (CF) patients, chicken yolk antibodies (IgY) could be used. The most significant advantage of IgY, in contrast to mammalian IgG, consists in the fact, that when bound to the antigen, they usually do not induce inflammatory reaction. In addition, the simplicity of egg production and the ease of IgY preparation makes this kind of antibody an excellent tool for passive immunization. Thus, the aim of our project was to study the effect of IgY and its Fab fragment on the potential induction of pro-inflammatory reactions in lung epithelial cells. METHODS Chicken IgY were prepared from pooled egg yolks. Fab fragmens of IgY were purified from the papain digest of IgY using DEAE-Sephacel ion exchange chromatography. Their purity was verified by SDS electrophoresis in polyacrylamide gel. Immortalized human cell lines, CuFi (CF patient) and NuLi (healthy subject), and A549 (human adenocarcinoma cells) were exposed to IgY, Fab, OVA, LPS (positive control), PBS (negative control), and human and goat IgG for 24 hours. The concentration of pro-inflammatory cytokines TNF-α, IL-1β, IL-6 and GM-CSF were determined in cell media using the BioPlex method, which enables the quantification of multiple analytes simultaneously in one sample. RESULTS Our results show that i) the Fab fragment induced levels of some proinflammatory cytokines, when compared to the PBS control, whereas ii) chicken IgYs did not induce any notable production of pro-inflammatory cytokines in contrast to intense effect of LPS on TNF-α and GM-CSF. In summary, our data show that levels of all cytokines are comparable with physiological values in human serum except of IL-1β, which concentration in cell medium was markedly elevated by Fab fragment. CONCLUSIONS The present data indicate that IgY are not inflammatory for lung cells and thus they are possibly applicable for prevention of airway bacterial infections.


title: Prevalence of antibodies against canine parvovirus and canine distemper virus in wild coyotes in southeastern Colorado.

text: Serum from 72 wild coyotes (Canis latrans) in southeastern Colorado (USA) was collected and analyzed for prevalence of antibody to canine parvovirus (CPV) and canine distemper virus (CDV) from 1985 to 1988. The prevalence of antibodies to CPV and CDV was 71% and 57%, respectively, for the 4 yr of the study. Prevalence of antibody to CPV did not differ among years, between sexes, or with age. Prevalence of antibody to CDV did not differ among years or between sexes, but was significantly higher in adults (62%) than juveniles (33%). Prevalence of antibodies against CPV and CDV in southeastern Colorado was comparable to results reported in other serologic surveys in the western United States.


title: Recent developments on coronavirus main protease/3C like protease inhibitors.

text: Coronaviruses have been thrust into the spotlight by the recurring novel human coronavirus infections following the 2003 SARS pandemic. In the years since the initial SARS outbreak, the arsenal to fight this virus family has been significantly increased by the rapid growth of coronavirus research. Among the potential viral drug targets, coronavirus 3C like proteases (3Cl) have emerged as the most popular drug target. A number of patented inhibitors with promising clinical potential have been developed via different methods of drug discovery, including virtual screening, natural product isolation and structure assisted rational drug design. This review serves as a summary of the progress in both the method of drug discovery and the related inhibitors against the coronavirus 3Cl protease.


title: Rapid increase in HIV rates--Orel Oblast, Russian Federation, 1999-2001.

text: During 1999-2001, the estimated number of cases of human immunodeficiency virus (HIV) reported officially in the Russian Federation increased approximately 16-fold, from 11,000 to 177,000. In 2001, of 49,434 HIV-infected persons for whom a risk factor was identified, 46,274 (94%) were injection-drug users (IDUs). However, the actual number of HIV-infected persons in Russia is estimated to be four to 10 times higher than reported. Rapid increases in HIV have been reported in urban areas (e.g., Kaliningrad, Moscow, and St. Petersburg) and also might be occurring in rural areas. During 1997-2000, HIV seroprevalence reportedly increased 33-fold in Orel Oblast, a predominantly rural, agricultural province (1999 population: 900,000) in central European Russia. To confirm and describe this increase and evaluate the risk for continued rapid increase of HIV, CDC collaborated with the Orel Oblast AIDS and Infectious Diseases Prevention Center (AIDS Center) to assess recent HIV trends and the prevalence of risk behaviors among IDUs in Orel Oblast. This report summarizes the results of that assessment, which indicate continued increases in HIV rates and underscore the need for interventions directed at IDUs and their sex partners to limit further spread of HIV.


title: Effects of Topical Antiseptic Solutions Used During Total Knee Arthroplasty on Suture Tensile Strength.

text: INTRODUCTION Irrigating a surgical wound with an antiseptic solution is commonly performed while suturing following a total knee arthroplasty (TKA) to help prevent wound complications. The purpose of this study was to: 1) evaluate the mean load to failure of different sutures, and 2) compare the mean load to failure of the sutures after soaking in four different antiseptic solutions. MATERIALS AND METHODS Load-to-failure tests were conducted on four sets of comparable sutures (eight sutures) from two different companies Ethicon Inc. (Somerville, New Jersey) and Covidien (Mansfield, Massachusetts). The four suture types included: 1) non-absorbable braided polyethylene, 2) absorbable braided glycolide or lactide polymer, 3) absorbable monofilament polydioxanone or polyglyconate, and 4) absorbable monofilament polyglecaprone or gylcomer. Sutures were tested for tensile strength at baseline (i.e., no solution; n=5 per suture), and were then soaked for five minutes in one of four different antiseptic solutions: 0.125% sodium hypochlorite, 4% chlorhexidine gluconate, 10% povidone-iodine, and a 1:1 ratio of 3% hydrogen peroxide and sterile water. Effects of the different solutions on individual sutures were assessed with analysis of variance, and pairwise comparison tests were performed with post-hoc Tukey tests. RESULTS For the controls, the mean failure loads for the type 1 sutures were 118.5 N and 120.3 N, for the type 2 sutures, 145.8 N and 155.4 N, the type 3 sutures, 103.8 N and 162.2 N, and the type 4 sutures, 86.9 N and 87.7 N. After being soaked in sodium hypochlorite, the mean failure load decreased for one of the type 2 sutures (mean difference, -12.8 N;p=0.003), while the other type 2 suture had a decreased failure load after soaking in povidone-iodine (mean difference, -10.3 N;p=0.041) and hydrogen peroxide (mean difference, -14.6 N;p=0.001). A type 1 suture had an increased load to failure after soaking in povidone-iodine (mean difference, 13.2 N;p<0.0001) and hydrogen peroxide (mean difference, 10.5 N;p<0.0001). CONCLUSION Certain sutures may have changes in their breaking point depending on what type of antiseptic solution is used for wound irrigation, but due to the small magnitude of change, this may not necessarily be clinically relevant.


title: Challenges in building health surveillance systems in saudi arabia.

text: This paper is aiming to briefly discuss the role of health surveillance system in strengthening public health at both the local and global level and the use of health informatics in effectively creating a database of health status for the population of Saudi Arabia. This review will specifically focus on the challenges that face the Kingdom of Saudi Arabia in order to effectively implement surveillance programs making use of advances in health information technology. Data collection was performed through a web-based retrieval of reports and articles and via an interview with an epidemiologist in the Saudi Ministry of Health Surveillance unit. Based on the results of this research, it was found that the use of technology has led to an improvement in communication between various stakeholders (e.g. clinicians, epidemiologists, and decision makers) by providing timely and accurate information needed for informed decision making. However, implementing an ideal model of surveillance systems in Saudi Arabia faces many challenges particularly in training healthcare providers to be qualified and competent enough to ensure the successful implementation of a disease surveillance system.


Exacerbations of chronic obstructive pulmonary disease: definition, aetiology and management.


title: Intravenous immunoglobulin G is remarkably beneficial in chronic immune dysschwannian/dysneuronal polyneuropathy, diabetes-2 neuropathy, and potentially in severe acute respiratory syndrome.

text: Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy is an autoimmune peripheral-nerve and/or nerve-root disorder known to usually respond to intravenous immunoglobulin-G treatment. Benefit can involve any combination of motor-nerve fibers and large and small sensory-nerve fibers responsible for a progressively crippling, unbalancing, discomforting or painful disorder. "Diabetic neuropathy" is commonly considered untreatable. However, 81% of my 48 recently-summarized type-2 diabetes patients with polyneuropathy, adequately-treated with intravenous immunoglobulin-G, off-label, were relieved, sometimes completely, of various motor and sensory symptoms, including pain, thereby resembling Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy. Spinal fluid protein in them is often elevated, higher values seeming to auger a better intravenous immunoglobulin-G response. Continuing the improvement requires continuing the intravenous immunoglobulin-G treatment, indicating both intravenous immunoglobulin-G responsiveness and dependency. The intravenous immunoglobulin-G responsive type-2 diabetes polyneuropathy usually is dysschwannian, sometimes mainly dysneuronal intravenous immunoglobulin-G, the most beneficial and safest treatment, is costly, but if intravenous immunoglobulin-G-treatability of a dysimmune component of type-2 diabetes neuropathy is overlooked, dismissed or rejected, as commonly happens, other costs are high regarding the patient's worsening morbidity and disability, and resultant need for increased medical care. A novel intravenous immunoglobulin-G regimen effective for fragile patients is Two Non-Consecutive-Days Every Week, using 0.4 gm/kg body wt/day. Possible molecular mechanisms of intravenous immunoglobulin-G benefit are discussed. I propose that a) there is a higher incidence of Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy-like neuropathy in type-2 diabetes patients and in patients with a strong family history of type-2 diabetes, and b) the intravenous immunoglobulin-G-treatable neuropathy in type-2 diabetes can be brought on by the genetico-diabetoid-2 state. The genetic-metabolic milieu (but not necessarily glucose dysmetabolism per se.) of type-2 diabetes putatively predisposes to the presumably-dysimmune intravenous immunoglobulin-G-responsive polyneuropathy. In some of our patients, especially ones having a strong type-2 diabetes genetic background, the intravenous immunoglobulin-G-responsive neuropathy preceded the diagnosis of type-2 diabetes by 5-10 years. Accordingly, Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy patients having a strong type-2 diabetes genetic background are designated "genetico-diabetoid-2 neuropathy" prior to their manifesting type-2 diabetes. Intravenous immunoglobulin-G is herein suggested as a treatment for Severe Acute Respiratory Syndrome, a recent, and feared-repetitive, pandemic with many fatalities caused by a highly-contagious mutant coronavirus, for which there is no definitive treatment. Intravenous immunoglobulin-G might: a) combat a dysimmune component of Severe Acute Respiratory Syndrome, including the reactive cytokine-chemokine storm against respiratory tissues; b) contain some antibodies effective against the coronavirus non-specific components of Severe Acute Respiratory Syndrome; c) block host-cell receptors for the virus; and d) counteract secondary infections.


title: Regulation of N-glycolylneuraminic acid biosynthesis in developing pig small intestine.

text: N -Glycolylneuraminic acid (Neu5Gc), an abundant sialic acid in animal glycoconjugates, is formed by the enzyme CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase. The amount of Neu5Gc relative to other sialic acids is highly dependent on the species, tissue and developmental stage. Although the activity of the hydroxylase is a key factor in controlling Neu5Gc incorporation in adult animals, little is known about the regulation of hydroxylase expression and the role of this enzyme in determining changes in Neu5Gc during development. Using pig small intestine as a model system, the appearance of total sialic acid and the regulation of Neu5Gc biosynthesis during development were studied in various regions of this tissue. The amount of total sialic acid and Neu5Gc declined markedly in 2 weeks after birth. Although in subsequent developmental phases there were no positional differences in total sialic acid, a significant proximal-to-distal increase in Neu5Gc was detected. In all cases, a good correlation between the amount of Neu5Gc, the activity of the hydroxylase and the level of hydroxylase mRNA was observed. However, Western-blot analysis revealed considerable accumulation of less active enzyme in the post partum period, which persisted until adulthood. No evidence for cytosolic factors influencing the hydroxylase activity or for the formation of truncated enzyme was found, raising the possibility that other regulatory mechanisms are involved. The relevance of these results in the formation of Neu5Gc as a receptor for certain pig enteric pathogens is also discussed.


COVID-19 Supply Chain Considerations for Prescription Drugs in Dermatology.


title: CD13/aminopeptidase N, a novel chemoattractant for T lymphocytes in pulmonary sarcoidosis.

text: CD13/aminopeptidase N (E.C.3.4.11.2) is an ectoenzyme located in the outer membrane of a variety of cells. Because aminopeptidase expression was shown to be upregulated by a Th1-related cytokine, IFN-gamma, we examined here the significance of CD13/aminopeptidase N in pulmonary sarcoidosis. The activity of aminopeptidase in bronchoalveolar lavage fluid (BALF) was significantly higher in patients with sarcoidosis than in normal volunteers (NV) and control patients (CP). The activity significantly correlated with lymphocyte percentages and the ratio of CD4+ to CD8+ T lymphocytes in the BALF, and was higher in patients with sarcoidosis with parenchymal involvement than in those without the involvement. CD13/aminopeptidase N protein, which has a molecular mass of approximately 150 kD, was detectable in alveolar macrophages (AM) from patients with sarcoidosis at higher levels than in those from NV. CD13/aminopeptidase N induced in vitro chemotactic migration of human lymphocytes in a concentration range of 10(-)(5) to 10(-)(1) U/ml. The chemotactic activity was greater for CD4+ T lymphocytes than for CD8+ T lymphocytes. The enzymatic activity of CD13/aminopeptidase N was responsible for the chemotactic activity because bestatin, an inhibitor of CD13/aminopeptidase N, abolished the chemotactic activity. Higher chemotactic activity for lymphocytes was detected in the BALF from patients with sarcoidosis than in that from NV, and the activity was significantly decreased by treatment with bestatin. This study indicates that CD13/ aminopeptidase N expressed in AM may have a role in T-lymphocyte involvement in the sarcoid lung and the pathogenesis of alveolitis in this disorder.


title: Recent animal disease outbreaks and their impact on human populations.

text: Over the past 20 years, headlines have documented an increasing number of emerging diseases; most have an animal source (zoonoses). Recent examples include West Nile virus, severe acute respiratory syndrome (SARS), avian influenza, and monkeypox. While some emerging diseases occur among both humans and animals, others affect only animals or only humans. Nevertheless, all these new or reemerging infections have societal implications, often tied to local and national economies. It is important to understand the implications of emerging animal diseases and encourage stronger collaboration of veterinary and medical practitioners, especially in rural areas. Illnesses in agricultural workers may be the index cases for newly emerging diseases.


title: Progress with enhancing veterinary surveillance in the United Kingdom.

text: The UK has experienced various animal health events that have had national impact in recent years. In response, a ;Veterinary Surveillance Strategy' (VSS) was published in 2003, with the objective of enhancing and coordinating national veterinary surveillance practice in a way that would enable important animal health events to be detected and assessed more rapidly and reliably. The VSS adopts an integrated UK-wide approach, which includes widespread engagement with interested parties both within government and beyond. It proposes enhancing surveillance through improved collaboration; transparent and defensible prioritisation of government resources to surveillance; deriving better value from existing resources, and assuring quality of the surveillance reports and source data. This article describes progress with implementing the VSS, in particular the methodology for developing a functional network and creating an effective, quality-assured, information management system, RADAR.


title: Protein structure prediction in structure based drug design.

text: The human genome and other genome sequencing projects have generated huge amounts of protein sequence information. Recently, a structural genomics project that aims to determine at least one representative three-dimensional structure from every protein family experimentally has been started. Homology modeling will play an essential role in structure based drug design such as in silico screening; because based on these representative structures the three-dimensional structures of the remaining proteins encoded in the various genomes can be predicted by homology modeling. The results of the last Critical Assessment of Techniques for Protein Structure Prediction (CASP5) demonstrated that the quality of homology modeling prediction has improved; reaching a level of reliability that biologists can now confidently use homology modeling. With improvements in modeling software and the growing number of known protein structures, homology modeling is becoming a more and more powerful and reliable tool. The present paper discusses the features and roles of homology modeling in structure based drug design, and describes the CHIMERA and FAMS modeling systems as examples. For a sample application, homology modeling of non-structural proteins of the severe acute respiratory syndrome (SARS) coronavirus is discussed. Many biological functions involve formation of protein-protein complexes; in which the protein molecules behave dynamically in the course of binding. Therefore, an understanding of protein-protein interaction will be very important for structure based drug design. To this end, normal mode analysis is useful. The present paper discusses the prediction of protein-protein interaction using normal mode analysis and examples of applications are given.


COVID-19 and gastrointestinal endoscopy in Belgium : uncertainty and ambiguity.


title: Gastrodin prevents steroid-induced osteonecrosis of the femoral head in rats by anti-apoptosis.

text: BACKGROUND Gastrodin, as one of the major components extracted from the Chinese herb Gastrodia elata Bl., has many biologic effects, one of which is anti-apoptosis. Apoptosis is considered to be one of the pathogenetic mechanisms in steroid-induced osteonecrosis of the femoral head (ONFH). Therefore, we performed this study to investigate whether gastrodin has the potential to prevent steroid-induced ONFH. METHODS All 18 male adult Wistar rats were divided equally into three groups: the steroid group, the gastrodin+steroid group, and the control group. Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone. Histomorphometric method was used to determine the incidence of osteonecrosis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was performed to detect apoptotic index of osteocytes and osteoblasts. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of Bax, Bcl-2, and Caspase-3. Fisher's exact probability test and one-way analysis of variance (ANOVA) with Turkey's post hoc test were used to examine significant differences between groups. RESULTS The incidence of osteonecrosis in the gastrodin+steroid group (16.7%) was significantly lower than that in the steroid group (83.3%). According to TUNEL assay, the apoptotic indices in the steroid group, the gastrodin+steroid group, and the control group were 91.1%, 27.1%, and 5.4%, respectively, and the differences were significant between groups. Compared with the control group and the gastrodin+steroid group, the mRNA and protein expression levels of Bax and Caspase-3 were significantly higher in the steroid group, but the Bcl-2 mRNA and protein expression levels were significantly lower. CONCLUSION Gastrodin could prevent steroid-induced ONFH by anti-apoptosis.


title: Categorization of North American porcine reproductive and respiratory syndrome viruses: epitopic profiles of the N, M, GP5 and GP3 proteins and susceptibility to neutralization.

text: Eleven epitopes were identified by murine monoclonal antibodies (MAbs) that represented the N, M, GP5 and GP3 proteins of the North American (NA) porcine reproductive and respiratory syndrome (PRRS) virus, KY 35 (NVSL 46907). Three discontinuous epitopes of the N and M proteins were designated EpORF7-Fd through Hd and EpORF6-Ad through Cd. Five continuous epitopes of the GP5 and GP3 proteins were designated EpORF5-A through C and EpORF3-A and B. The MAbs representing EpORF5-C and EpORF6-A and B had neutralizing activity. The MAbs representing the above epitopes, except EpORF7-Gd and Hd, expanded the virus marker system described in a previous study in which a panel of 69 NA viruses and the Lelystad virus were categorized into 5 antigenic groups, I15 through V15 based on the presence or absence of 5 continuous epitopes of the N protein. Antigenic groups I15 and II15, which represented 84.7 and 11.6% of all viruses tested, were categorized further into 9 and 4 subgroups, respectively. The remaining NA viruses and the Lelystad virus were distributed among 4 groups, one of which was represented by 2 subgroups. Significant (P<0.05) differences in sensitivity to neutralization of 28 viruses representing 6 antigenic groups by the 3 neutralizing MAbs suggested that sensitivity to neutralization may also be of value in categorizing PRRS viruses.