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Abstract The coronavirus disease 2019 (COVID-19) causes a systemic illness that can result in various manifestations. In addition to severe acute respiratory syndrome, patients often exhibit complications unrelated to the respiratory system. Potential liver damage can occur in 14.8 to 53.0% of the affected patients. Liver impairment in COVID-19 can also occur because of the use of polypharmacy during disease management. It is essential to be aware of drug-induced liver injury (DILI) in patients diagnosed with COVID-19, especially when considering the off-label usage of medications in both preventative and therapeutic regimens used on a wide scale. This review aims to give pertinent information regarding drugs utilized thus far in COVID-19 patients and their potential toxicity to the liver. We also present a suggested management approach to DILI in COVID-19 patients and lessons learned from the pharmacological management of this pandemic.

Current agricultural and food production practices are facing extreme stress, posed by climate change and an ever-increasing human population. The pressure to feed nearly 8 billion people while maintaining a minimal impact on the environment has prompted a movement toward new, more sustainable food sources. For thousands of years, both the macro (seaweed and kelp) and micro (unicellular) forms of algae have been cultivated as a food source. Algae have evolved to be highly efficient at resource utilization and have proven to be a viable source of nutritious biomass that could address many of the current food production issues. Particularly for microalgae, studies of their large-scale growth and cultivation come from the biofuel industry; however, this knowledge can be reasonably translated into the production of algae-based food products. The ability of algae to sequester CO2 lends to its sustainability by helping to reduce the carbon footprint of its production. Additionally, algae can be produced on non-arable land using non-potable water (including brackish or seawater), which allows them to complement rather than compete with traditional agriculture. Algae inherently have the desired qualities of a sustainable food source because they produce highly digestible proteins, lipids, and carbohydrates, and are rich in essential fatty acids, vitamins, and minerals. Although algae have yet to be fully domesticated as food sources, a variety of cultivation and breeding tools exist that can be built upon to allow for the increased productivity and enhanced nutritional and organoleptic qualities that will be required to bring algae to mainstream utilization. Here we will focus on microalgae and cyanobacteria to highlight the current advancements that will expand the variety of algae-based nutritional sources, as well as outline various challenges between current biomass production and large-scale economic algae production for the food market.

Background and rationale: Spontaneous bacterial peritonitis (SBP) stands as a primary complication and the most common bacterial infection in individuals suffering from decompensated liver cirrhosis. It is linked to substantial morbidity and mortality rates. The study aimed to determine the level of MCP-1 gene expression in the ascitic fluid of liver cirrhotic patients with or without SBP to evaluate its role in SBP diagnosis and to evaluate the role of ascitic fluid (AF) calprotectin as a diagnostic biomarker for SBP in liver cirrhosis (LC) patients. Methods: A cross-sectional hospital-based study was conducted at Internal Medicine, Gastroenterology and Hepatology Unit at AL-Rajhi Hospital in the period between 2020 and 2022. Participants were divided into two groups, a SBP group (n = 37) and a non-SBP group (LC patients with ascites only) (n = 48). AF levels of MCP-1, calprotectin and blood chemistry tests were estimated in all patients. Results: Both studied groups had no significant differences as regards demographic and laboratory data, except lower potassium levels among the SBP group. Monocyte chemoattractant protein-1 (MCP-1) was significantly higher among the SBP group (p= 0.000) compared to the non-SBP group. Also, both groups had significant differences as regards calprotectin (p= 0.01). Only three patients in the SBP group had positive ascitic fluid cultures (Escherichia coli, Klebsiella pneumonia, and Acinetobacter baumannii) while the non-SBP groups were negative for bacterial growth. Only in the control group, did MCP-1 have a positive correlation with serum albumin and total bilirubin. Conclusion: Ascitic fluid MCP-1 and calprotectin are considered promising biomarkers for early diagnosis of SBP.

Abstract Background Applying deep learning to digital histopathology is hindered by the scarcity of manually annotated datasets. While data augmentation can ameliorate this obstacle, its methods are far from standardized. Our aim was to systematically explore the effects of skipping data augmentation; applying data augmentation to different subsets of the whole dataset (training set, validation set, test set, two of them, or all of them); and applying data augmentation at different time points (before, during, or after dividing the dataset into three subsets). Different combinations of the above possibilities resulted in 11 ways to apply augmentation. The literature contains no such comprehensive systematic comparison of these augmentation ways. Results Non-overlapping photographs of all tissues on 90 hematoxylin-and-eosin-stained urinary bladder slides were obtained. Then, they were manually classified as either inflammation (5948 images), urothelial cell carcinoma (5811 images), or invalid (3132 images; excluded). If done, augmentation was eight-fold by flipping and rotation. Four convolutional neural networks (Inception-v3, ResNet-101, GoogLeNet, and SqueezeNet), pre-trained on the ImageNet dataset, were fine-tuned to binary classify images of our dataset. This task was the benchmark for our experiments. Model testing performance was evaluated using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve. Model validation accuracy was also estimated. The best testing performance was achieved when augmentation was done to the remaining data after test-set separation, but before division into training and validation sets. This leaked information between the training and the validation sets, as evidenced by the optimistic validation accuracy. However, this leakage did not cause the validation set to malfunction. Augmentation before test-set separation led to optimistic results. Test-set augmentation yielded more accurate evaluation metrics with less uncertainty. Inception-v3 had the best overall testing performance. Conclusions In digital histopathology, augmentation should include both the test set (after its allocation), and the remaining combined training/validation set (before being split into separate training and validation sets). Future research should try to generalize our results.

Recombinant production of viral proteins can be used to produce vaccine antigens or reagents to identify antibodies in patient serum. Minimally, these proteins must be correctly folded and have appropriate post-translation modifications. Here we report the production of the SARS-CoV-2 spike protein Receptor Binding Domain (RBD) in the green algae Chlamydomonas. RBD fused to a fluorescent reporter protein accumulates as an intact protein when targeted for ER-Golgi retention or secreted from the cell, while a chloroplast localized version is truncated. The ER-retained RBD fusion protein was able to bind the human ACE2 receptor, the host target of SARS-CoV-2, and was specifically out-competed by mammalian cell-produced recombinant RBD, suggesting that the algae produced proteins are sufficiently post-translationally modified to act as authentic SARS-CoV-2 antigens. Because algae can be grown at large scale very inexpensively, this recombinant protein may be a low cost alternative to other expression platforms.

Introduction: The terminal ventricle, also known as the fifth ventricle, is a tiny relic cavity in the conus medullaris of the human spinal cord. Our purpose in bringing attention to this condition is to get the word out about the signs and symptoms, diagnostic hurdles, and therapeutic options available for it. Methods: All relevant studies involving patients diagnosed with ventriculus terminalis (VT) were retrieved from PubMed, Google Scholar, and Scopus. Studies published in complete English language reports were included. The terms VT, terminal ventricle, and 5th ventricle. Age, gender, presenting symptoms, magnetic resonance imaging findings, treatment, and outcome of patients with ventriculus terminalis were all included and recorded. Results: The average age of the patients was 39 years, and there were 13 men among them (14.4%). Motor deficits and sciatica were the most commonly reported symptoms in 38 and 34 patients (42.2%, 37.7%), respectively. In 48 patients (53.3%), cyst fenestration was performed, and in 25 patients (27.7%), myelotomy was performed. Fifty-eight patients (64.4%) saw a reduction in cyst size after surgery. The majority of patients reported an improvement in their symptoms in 64 cases (51.1%), with only three cases (3.3%) reporting a worsening. Conclusions: In cases where the VT is the source of symptoms such as motor, sensory, or bladder dysfunction, surgical intervention is recommended. This review compiles information from the available literature to shed light on the anatomy, clinical presentation, imaging, and treatment options for this variant. It also aims to pinpoint any potential drawbacks or restrictions connected to the surgical techniques.

Abstract Nanoparticles (NPs) supplementation to biodigesters improves the digestibility of biowaste and the generation of biogas. This study investigates the impact of innovative nanoadditives on the microbiome of biodigesters. Fresh cow manure was anaerobically incubated in a water bath under mesophilic conditions for 30 days. Three different NPs (zinc ferrite, zinc ferrite with 10% carbon nanotubes and zinc ferrite with 10% C76 fullerene) were separately supplemented to the biodigesters at the beginning of the incubation period. Methane and hydrogen production were monitored daily. Manure samples were collected from the digesters at different time points and the microbial communities inside the biodigesters were investigated via real‐time PCR and 16 S rRNA gene amplicon‐sequencing. The results indicate that zinc ferrite NPs enhanced biogas production the most. The microbial community was significantly affected by NPs addition in terms of archaeal and bacterial 16 S rRNAgene copy numbers. The three ZF formulations NPs augmented the abundance of members within the hydrogenotrophic methanogenic phyla Methanobacteriaceae. While Methanomassiliicoccacaea were enriched in ZF/C76 supplemented biodigester due to a significant increase in hydrogen partial pressure, probably caused by the enrichment of Spirochaetaceae (genus Treponema). Overall, NPs supplementation significantly enriched acetate‐producing members within Hungateiclostridiaceae in ZF/CNTs, Dysgonomonadaceae in ZF and Spirochaetaceae ZF/C76 biodigesters.

Histone deacetylase inhibitors (HDACIs) act as anti-proliferative agents by promoting differentiation and inducing apoptosis. Valproic acid (VPA) is a HDACI that shows promising chemotherapeutic effect in a number of tumor cells. The present study aimed to investigate the inhibitory effect of VPA on the viability of mammary cancer cells and its enhancing effect with methotrexate (MTX) in vitro and in vivo. Treatment with VPA or MTX alone induced concentration-dependent cytotoxic effects in two breast cancer cell lines. Valproic acid increased significantly the cytotoxicity of MTX three times against MCF7. Valproic acid addition to MTX, however, did not produce any significant changes on MTX cytotoxicity against MDA-MB231. VPA (150 and 200 mg/kg) significantly inhibited the growth of Ehrlich ascites carcinoma (EAC) and solid Ehrlich carcinoma (SEC) tumor mouse models and improved results were achieved for tumor inhibition when VPA was combined with MTX (1 and 2 mg/kg) in vivo. The antitumor activity was not associated with a significant increase in toxicity or mice mortality rate. All these findings suggest that the combination of MTX and VPA may have clinical and (or) adjuvant therapeutic application in the treatment of mammary cancer. Key words: antitumor, valproic acid, methotrexate Les inhibiteurs de l'histone desacetylase (IHDAC) agissent comme des agents contre la proliferation cellulaire en favorisant leur differenciation et en entrainant leur apoptose. L'acide valproique (AVP) est un IHDAC dont les effets chimiotherapeutiques contre plusieurs cellules tumorales sont prometteurs. La presente etude portait sur l'effet inhibiteur de l'AVP sur la vitalite des cellules du cancer du sein ainsi que sur l'amplification de ceux du methotrexate (MTX) in vitro et in vivo. L'administration d'AVP ou de MTX en monotherapie entrainait des effets cytotoxiques proportionnels a la concentration dans deux lignees cellulaires de cancer du sein. L'AVP entrainait une augmentation marquee trois fois plus importante de la cytotoxicite du MTX contre les cellules MCF7. Cependant, l'ajout d'AVP au MTX n'entrainait aucune variation notable quant a la cytotoxicite du MTX contre les cellules MDA-MB231. L'AVP (a 150 et a 200 mg/kg) entrainait une inhibition marquee de la croissance dans les modeles tumoraux de cellules IP et S-C de carcinome ascitique d'Ehrlich chez la souris, avec une amelioration des resultats quant a l'inhibition des tumeurs lorsque l'AVP etait administre en association avec le MTX (a 1 et a 2 mg/kg) in vivo. L'activite antitumorale n'etait pas associee avec une augmentation notable de la toxicite ou du taux de mortalite chez les souris. Tous ces resultats laissent entendre que l'association du MTX avec l'AVP pourrait avoir des applications therapeutiques cliniques et/ou adjuvantes dans le traitement du cancer du sein. [Traduit par la Redaction] Mots-cles : agent antitumoral, acide valproique, methotrexate, 1. Introduction Breast cancer (BC) is the most common type of cancer, impacting 2.1 million women yearly and causing the greatest cancer-related deaths among women (Elatar 2001). It is the [...]

Abstract Introduction Osteoporosis is characterized by deterioration of bone microarchitecture and reduced bone mass and can increase the risk of fracture. To reduce this risk, the aim of this study was to compare the combination effects of olive oil and Lepidium sativum compared to the conventional drug therapy alendronate. Methods Osteoporosed-induced rat model was established by administration of dexamethasone in female adult albino rats. The serum level of Ca2+, P3+, and osteocalcin was assessed. In addition, histopathological changes and immunohistochemical expression of osteopontin within bone specimens were performed. Results Our results showed that a combination of olive oil and Lepidium sativum had a beneficial therapeutic effect in the treatment of osteoporosis as compared to alendronate therapy. This was demonstrated by increase of serum Ca2+, P3+, and osteocalcin levels in treated compared to control groups. Intriguingly, the highest effect was noticed in rats that received a combination of olive oil and Lepidium sativum compared to the individual treatment. This was reflected by an increase in the cortical bone thickness and a decrease in immunohistochemical expression of osteopontin compared to individual treated groups. Conclusion We concluded that the administration of a combination of olive oil and Lepidium sativum improves bone mineral health and intensity and reduces the risk of osteoporosis in a rat model.

Background:Healthy obesity means obese individuals remain free of metabolic health complications. Several researches link microbiota changes to obesity, focus on metabolic role of IL-6 and its ability to alter fat metabolism and correlate circulating calprotectin concentration to morbid obesity. This study evaluated the relative abundance of gut microbiota (Prevotella and γ-Proteobacteria), estimated the serum levels of inflammatory mediators (IL-6 and calprotectin) and studied the correlation between them in healthy obese and normal weight adults. Methods: 33 healthy obese (HO) and 14 normal weight (NW) controls were included. Serum levels of IL-6 and calprotectin were estimated by ELISA. Abundances of Prevotella and γ-Proteobacteria were determined in stool using real time PCR. Results: IL-6 and calprotectin levels were significantly lower in HO than in NW (p=0.001, p=0.001 respectively) with significant negative correlation between IL-6 and body mass index (BMI) in HO (r=-0.438, p=0.011) and negative but statistically insignificant correlation with BMI in NW groups (r=-0.024, p=0.935). There was negative but statistically insignificant correlation between calprotectin and BMI in HO (r=-0.075, p=0.677) and NW (r=-0.381, p=0.179). Prevotella and γ-Proteobacteria abundances were higher in HO than in NW and insignificant (p=0.31, p=0.55 respectively) with significant positive correlation between Prevotella and γ-Proteobacteria abundance in HO (r=0.436, p=0.011), positive and insignificant correlations between abundance of Prevotella and levels of IL-6 in HO and NW (r=0.303, P=0.086 vs r=0.316, p=0.272 respectively). Conclusion: IL-6 and calprotectin have role in regulation of energy homeostasis. Elevated abundances of Prevotella and γ-Proteobacteria may be the primary shifts in gut microbiota of HO.

Abstract Background Chronic renal failure (CRF) is a progressive loss of renal function that lead to reduced sodium filtration and inappropriate suppression of tubular reabsorption that ultimately leads to volume expansion. The aim of this study was to study the efficacy of furosemide and tadalafil nanoforms compared to conventional forms against adenine-induced CRF rat-model. Methods Addition of 0.75% adenine to the diet of rats for 4 weeks gained general acceptance as a model to study kidney damage as this intervention mimicked most of the structural and functional changes seen in human chronic kidney disease Urine analysis, histopathological changes and immunohistochemical expression of caspase-3 and interleukin-1 beta (IL-1β) in renal tissues were performed. Results Our results showed that the combination of tadalafil and furosemide using conventional and nanoparticle formulations had better renoprotective effect than individual drugs. This was demonstrated by improvement of urinary, serum and renal tissue markers as indicative of organ damage. This was also reflected on the reduction of tubular expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Immunohistochemical studies showed that the deteriorated renal cellular changes indicated by increased expression of caspase-3 and IL-1β were greatly improved by the combined treatment particularly with the nanoforms. Conclusions The nanoforms of both furosemide and tadalafil had greater renopreventive effects compared with conventional forms against adenine-induced CRF in rats.

Abstract Background Intermittent fasting (IF) during the month of Ramadan is part of the religious rituals of Muslims. The effect of intermittent fasting on disease activity in inflammatory bowel diseases (IBD) is still unknown. This is the first study to assess the effect of IF during Ramadan on inflammatory markers in patients diagnosed with IBD. The effects on clinical disease activity, quality of life, and levels of depression were also assessed. Methods Patients diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) who intended to observe Ramadan fasting were recruited. The following were assessed immediately before and at the end of Ramadan: Serum CRP and stool calprotectin, partial Mayo score, Harvey Bradshaw index (HBI), Simple IBD questionnaire (SIBDQ), and Hamilton depression scale questionnaire. Results 80 patients diagnosed with IBD were recruited (60 UC, 20 CD). Serum CRP and stool calprotectin did not show a significant change before vs after fasting (median CRP 0.53 vs 0.50, P value = 0.27, Calprotectin 163 vs 218 respectively, P value = 0.62). The partial Mayo score showed a significant rise after fasting (median 1 before vs 1 after fasting, mean: 1.79 vs 2.33 respectively, P value = 0.02). Harvey-Bradshaw index did not show a significant change after fasting (median 4 vs 5, P value = 0.4). Multiple linear regression revealed that older age and a higher baseline calprotectin were associated with a higher change in Mayo score after fasting (P value = 0.02 and P value = 0.01, respectively). No significant change was detected in SIBDQ or Hamilton depression scale scores. Conclusions In patients diagnosed with UC, IF during Ramadan was associated with worsening of clinical parameters, the effect was more pronounced in older patients and those with higher baseline calprotectin levels. However, IF during Ramadan was not associated with an adverse effect on objective inflammatory markers (CRP and calprotectin).

Reham Samir, Mohamed B Hashem, Hedy A Badary, Ahmed Bahaa, Nader Bakheet Endemic Medicine Department, Cairo University, Cairo, EgyptCorrespondence: Mohamed B Hashem, Email Mohamed.bassam@kasralainy.edu.egAbstract: Acute intramural hematoma of the colon is a rarely encountered clinical condition with diverse precipitating factors. Different acute and chronic complications emerge following hematoma formation, mandating high clinical suspicion for early diagnosis and optimum management. CECT represents the cornerstone for the proper demonstration of colonic hematomas and possible detection of complications as well as the underlying etiology. There are multiple strategies for management of intramural hematoma and treatment should be tailored according to the etiology and the clinical condition of the patient, reserving surgical intervention for unstable or complicated cases. Endoscopic management of colonic hematomas offers a promising minimally invasive modality with potential safety and efficacy.Keywords: intramural hematoma, endoscopy, colonic hematoma

Mona Gaber,1 Lamia Ahmed A Galal,1 Haiam Mohamed Mahmoud Farrag,1,2 Dalia M Badary,3 Samia S Alkhalil,2 Nahed Elossily1 1Department of Parasitology, Faculty of Medicine, Assiut University, Assiut, Egypt; 2Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Shaqra University, Shaqra, Kingdom of Saudi Arabia; 3Department of Medical Pathology, Faculty of Medicine, Assiut University, Assiut, EgyptCorrespondence: Mona GaberDepartment of Parasitology, Faculty of Medicine, Assiut University, Assiut, 71515, EgyptTel +2088360163Email m.g.mostafa@aun.edu.eg; monahadea@gmail.comBackground: Waterborne cryptosporidiosis is the second cause of diarrhea in young children and immunocompromised hosts after rotavirus. Except for nitazoxanide (NTZ), there is no accredited cryptosporidiosis treatment to date. Therefore, there is an urgent need to find an effective and safe treatment for cryptosporidiosis. This study aimed to investigate the possible anti-protozoal effects of Syzygium aromaticum (clove) oil, Anethum graveolens (dill) seeds oil, Lactobacillus acidophilus LB, and zinc against Cryptosporidium parvum in comparison to NTZ.Methods: Besides the negative control, mice from six experimental groups (T1–T6) were infected with Cryptosporidium parvum oocysts. On the seventh day post-infection (PID), mice from five groups were treated for 8 consecutive days with NTZ, clove oil, dill seed oil, Lactobacillus acidophilus LB, and zinc commercial forms (T2–T5). Oocysts shedding rate, differences of mice body weight, serum IL10, and TNF-α, cryptosporidial antigen, and cd3 at the intestinal mucosa were evaluated at the end of the experiment.Results: The mean of the C. parvum oocysts’ shedding rate was significantly lower in all treated groups than in the non-treated group. The oocysts reduction rate was the highest in zinc-treated mice (98.3%), Lactobacillus acidophilus LB and dill-treated groups (95.77%), and the NTZ-treated group (91.55%). Clove oil was the least effective, with a 74.65% reduction rate. Excluding the clove oil-treated group, immunohistochemical analysis revealed the clearance of the Cryptosporidium antigen in the intestinal tissue in all treated groups.Conclusion: The study has provided a rational basis for using these safe, cheap, and commercially available alternatives in treating cryptosporidiosis combined with NTZ.Keywords: Cryptosporidium parvum, Syzygium aromaticum, Anethum graveolens seeds oil, Lactobacillus acidophilus LB, zinc, nitazoxanide

Current agricultural and food production practices are facing extreme stress, posed by climate change and an ever-increasing human population. The pressure to feed nearly 8 billion people while maintaining a minimal impact on the environment has prompted a movement toward new, more sustainable food sources. For thousands of years, both the macro (seaweed and kelp) and micro (unicellular) forms of algae have been cultivated as a food source. Algae have evolved to be highly efficient at resource utilization and have proven to be a viable source of nutritious biomass that could address many of the current food production issues. Particularly for microalgae, studies of their large-scale growth and cultivation come from the biofuel industry; however, this knowledge can be reasonably translated into the production of algae-based food products. The ability of algae to sequester CO2 lends to its sustainability by helping to reduce the carbon footprint of its production. Additionally, algae can be produced on non-arable land using non-potable water (including brackish or seawater), which allows them to complement rather than compete with traditional agriculture. Algae inherently have the desired qualities of a sustainable food source because they produce highly digestible proteins, lipids, and carbohydrates, and are rich in essential fatty acids, vitamins, and minerals. Although algae have yet to be fully domesticated as food sources, a variety of cultivation and breeding tools exist that can be built upon to allow for the increased productivity and enhanced nutritional and organoleptic qualities that will be required to bring algae to mainstream utilization. Here we will focus on microalgae and cyanobacteria to highlight the current advancements that will expand the variety of algae-based nutritional sources, as well as outline various challenges between current biomass production and large-scale economic algae production for the food market.

Background: Healthcare workers (HCWs) are a presumed high-risk population for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Identifying factors associated with seroprevalence can help establish better practices in healthcare settings. In this study, we evaluate prevalence of SARS-CoV-2 infection among previously undiagnosed HCWs and describe profiling of antibody responses against SARS-CoV-2, including neutralizing antibodies (NAbs). Methods: We analyzed a cohort of 386 HCWs in a university hospital in Egypt and 725 volunteers not affiliated to any healthcare facility (non-healthcare workers - NHCWs). Participants provided a nasopharyngeal swab and serum samples for SARS-CoV-2 nucleic acid and SARS-CoV-2-specific antibodies, respectively. HCWs who tested positive by either test were sequentially monitored. Results: At baseline, point prevalence of viral carriage was 11.4% in HCWs (n = 44/386) and 11.9% in NHCWs (86/725). The cumulative prevalence of SARS-CoV-2 infection among HCWs considering all studies was 25.6%, which was statistically lower than in NHCWs (41.0%). Prevalence was greatest among janitorial staff (45.9%) and the most affected departments were gastroenterology (31.1%), and emergency medicine (30.0%). Prior anosmia, fever or headache were associated with higher odds of positivity for SARS-CoV-2 infection. Regarding serial antibody measurements, RT-PCR-positive HCWs displayed IgG detection rates of 29.5%, 70% and 60% at visit 1, visit 2 and visit 3, respectively with slow decline of median IgG antibody titers, whereas, corresponding detection rates for total Ig antibodies were 50%, 90.3%, and 88.9%, respectively with increasing median titers. NAbs measured at each time point were positively correlated with total Ig levels, whereas IgG levels were positively correlated with NAbs at visit 1 and visit 3. Conclusion: Our results demonstrate lower cumulative prevalence of SARS-CoV-2 infection in HCWs than general population and suggest that asymptomatic HCWs exhibit considerable IgG and total Ig antibodies response as well as NAbs for up to 120 days, with positive correlation in between.