Salmonella Choleraesuis and Salmonella Typhimurium bacterins in pigs. Two experimental groups were formed: G1, animals immunized with two doses of a commercial vaccine (n = 20); G2, control group (n = 20). After vaccination, all pigs were orally challenged (D0) with 108 CFU of Salmonella Typhimurium and evaluated for 40 days. Every 10 days after D0, five piglets from each experimental group were euthanized and submitted to the necroscopic examination, when organ samples were collected. Blood samples and rectal swabs were collected before the first dose of the vaccine (D−42), before the second dose (D−21), before the challenge (D0), and thereafter, every three days until D39. Blood count, serum IgG measurement by ELISA, and the excretion of Salmonella Typhimurium in feces were evaluated. While the results from blood count and serum IgG concentration did not differ, the detection and excretion of Salmonella between G1 and G2 differed (p < 0.05). Therefore, it was observed that this vaccine partially protected the animals against experimental infection with Salmonella Typhimurium, reducing the excretion of bacteria in feces.Since the occurrence of swine salmonellosis has increased over time and control strategies other than biosecurity are highly recommended, the present study aimed to evaluate the efficacy of vaccination with  Salmonella infection in pigs was first reported in 1886 by Salmon and Smith when Salmonella Choleraesuis was associated with hog cholera [Salmonella have been reported, affecting a wide range of animals, including humans [Salmonella spp. consists of only two species, Salmonella enterica and Salmonella bongori, in which S. enterica is divided into six subspecies: S. enterica subsp. enterica, S. enterica subsp. salamae, S. enterica subsp. arizonae, S. enterica subsp. diarizonae, S. enterica subsp. houtenae, and S. enterica subsp. indica [Salmonella enterica species, at least 1576 are classified as Salmonella enterica subsp. enterica, which also includes S. Choleraesuis (SC) and S. Typhimurium (ST), the most important serovars in pig production worldwide [g humans . The gen. indica . From thorldwide ,3.Salmonella Typhimurium, a non-host-specific Salmonella, recently became the most common serovar isolated from pigs in Europe, the United States, and Brazil [d Brazil ,5,6,7, ad Brazil ,9. The cd Brazil . Salmonella Choleraesuis infection in swine is known for causing generalized sepsis in affected animals, which rarely show signs of diarrhea. At the beginning of the infection, pigs appear lethargic, febrile, and hardly move around the pen, and overall mortality tends to be high [On the other hand,  be high ,10. Even be high ,9,11,12.Swine salmonellosis is highly prevalent in the main pork production countries; thus, its control is critical, especially at the herd level ,13,14,15Salmonella infection in pigs. It is known that the innate and adaptative immune response against Salmonella are crucial for overcoming the infection in the host [Salmonella infection [Salmonella antibodies are necessary to a vaccine-induced resistance, which indicates that the development of resistance against Samonella following vaccination depends on the interaction between T and B cells [Vaccines that stimulate both innate and acquired immunity have a better chance of suppressing the the host . While tnfection ,20,21. ISalmonella spp. in feces and organs of infected and non-infected pigs; however, the outcome may differ according to the composition of the vaccine in question. Moreover, it was shown that the use of attenuated and inactivated vaccines against Salmonella spp. in pigs provide similar estimates of efficacy [According to de la Cruz et al. , most stefficacy . Such efefficacy .Salmonella Choleraesuis and Salmonella Typhimurium vaccine in experimentally infected piglets through the detection of Salmonella spp. in feces and organs as well as through serological evaluation of immunoglobulin G (IgG) concentration.Therefore, the present study aimed to assess the efficacy of an inactivated (bacterin) Salmonella and with good biosecurity measures and located near the municipality of Jaboticabal-SP.The research work was approved by the Ethics Committee on the Use of Animals (CEUA) of the School of Agricultural and Veterinary Sciences (FCAV/UNESP)-Jaboticabal Campus, under the protocol No 014844/19. For this study, 40 weaned piglets were used, 20 males and 20 females, 21 days old, obtained from a previously selected farm, free of The animals were transported to the Swine Medicine Laboratory at the FCAV/UNESP-Jaboticabal Campus and housed in collective pens, where they received adequate food for the nutritional requirements of the nursery phase and water ad libitum.Salmonella Choleraesuis, Pasteurella multocida, and Salmonella Typhimurium inactivated by formalin and suspended into fenicated physiological serum, according to the manufacturer’s recommendations. While the animals in G1 received the commercial vaccine, the animals in group 2 (G2) were not immunized, serving as the control group. The piglets were randomly assigned to two experimental groups, consisting of 20 animals each. The animals of group 1 (G1) were immunized subcutaneously with two doses  of a vaccine against swine pneumoenteritis , containing strains of 8 colony forming units (CFU) of Salmonella Typhimurium and evaluated for the subsequent 40 days. The inoculum was prepared according to the recommendations of Wood et al. [Salmonella Typhimurium (RL0971/09) originally isolated from swine feces and naturally resistant to nalidixic acid.Twenty-one days after the second dose of the vaccine (D0), all 40 animals were orally inoculated with 10d et al.  and Olivd et al. , from a Salmonella excreted by pigs, after oral inoculation, showed the same pattern of sensitivity or resistance to the antibiotics tested with the strain used in the preparation of the inoculum.The strain used as the inoculum was subjected to the antimicrobial sensitivity test on Mueller–Hinton agar , by the Kirby–Bauer method , using cThe collection of blood samples and rectal swabs was performed before the vaccination, on D–42 and on D–21, and before the inoculation (D0). After that, the samples were collected every three days until the thirty-ninth day after inoculation (D39). Blood samples were collected by the puncture of the jugular vein after antisepsis with 70% alcohol, using the vacuum collection system , while the fecal samples were collected directly from the rectum of the animals with the aid of sterile swabs and immediately placed into tubes with 10 mL of cystine selenite broth (CS)  and incubated for 24 h at 37 °C. Blood samples were collected into sterile tubes containing ethylenediaminetetraacetic acid (EDTA) for performing a blood count and into sterile tubes without anticoagulant for serum IgG measurement. Immediately before sampling, the piglets were weighed and subjected to physical examination .Every 10 days after D0 , five piglets from each experimental group were euthanized according to the guidelines of the National Council for the Control of Animal Experimentation (CONCEA) and submitted to the necroscopic examination. Samples of lungs, liver, spleen, mesenteric lymph nodes, ileum, cecum, and ileocolic lymph nodes were collected aseptically, placed into sterile plastic bags , and kept under refrigeration until processing.For all blood samples collected with EDTA anticoagulant, red blood cell count, leukocyte and platelet counts, globular volume, hemoglobin content, and hematimetric indexes, including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC), were measured in an automatic device , following the manufacturer’s instructions. The differential leukocyte count was performed based on blood smear count of 100 cells, stained with modified Rosenfeld stain, under optical microscopy, according to Thrall .Serum IgG concentration was assessed using a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit , according to the manufacturer’s recommendations, in seven specific moments: D–42, D–21, D0, D9, D18, D30, and D39. All plates were read under 450 nm, in an iMark Microplate Reader .Salmonella genus were biochemically tested using triple sugar iron agar (TSI)  and lysine iron agar (LIA) . Then, slide-agglutination was performed using Salmonella polyvalent anti-somatic (anti-O) serum and serogroup B somatic anti-antigen serum , which included S. Typhimurium.After fecal collection and the selective enrichment stage, 10 µL of Selenite Cystine (SC) broth  was transferred to plates containing modified-brilliant green agar  with 50 μg/mL of nalidixic acid and then incubated for 24 h more at 37 °C [Organ samples were pre-enriched in 2% buffered water  in a 1:10 ratio before the selective enrichment step. The samples were homogenized and incubated for 24 h at 37 °C. Subsequently, 1 mL aliquots were transferred to tubes containing 9 mL of CS broth, incubated, and processed under the same abovementioned conditions.t-test for comparison between pairs of means at the level of 5% of significance using the Statistical Analysis System (SAS) program  after assessment of normality by the Shapiro–Wilk test. The variables that did not present a normal distribution were submitted to nonparametric analysis of variance using the Mann–Whitney test for comparison between pairs of means at the level of 5% of significance using the statistical program GraphPad Prism (Version 3.0). The results of microbiological isolation were compared using the chi-square test and, when necessary, Fisher’s exact test was applied [The results regarding blood count, rectal temperature, body weight, and serum IgG concentrations were subjected to analysis of variance (ANOVA) and Student’s  applied .The physical examination results of piglets  are shown in p > 0.05). There were also no differences in the body weight of the animals from the two experimental groups over the evaluation period . During the experimental period, 46 episodes of diarrhea were observed in animals from G1 , with 32 mild cases and 14 moderate cases. In animals from G2, 58 episodes of diarrhea  were observed, 43 of which were mild, 14 were moderate and 1 was severe. There was no difference between groups  and platelet count are shown in Regarding the hematimetric index, significant differences were observed in the MCV and MCH values between groups G1 and G2 at D–42 and in MCHC values at D–42 and D–21. However, these values remained within the range considered normal for swine species. No differences were observed in number of platelets of the animals from two experimental groups .3/µL). Only the animals of G2 showed average values for the number of leukocytes above the range considered normal for swine species.The results of leukocyte count and differential leukocyte count  are detailed in As for differential leukocyte count, significant differences were observed in lymphocyte count between the two experimental groups at D6 and D12, with higher counts being observed in animals from G2. Significant differences were also observed in the eosinophil count between G1 and G2 groups in D0, in rod neutrophil count in D12, and in monocyte count at D–42 and D3, but all counts remained within the range considered normal for swine species. There were no differences in the number of basophils and segmented neutrophils in animals from the two groups .8 CFU of Salmonella Typhimurium (D0) and at 9 (D9), 30 (D30), and 39 (D39) days after inoculation using the ELISA technique (No difference was observed in serum IgG concentration of immunized (G1) and non-immunized (G2) animals with swine pneumoenteritis vaccine, before the first dose of vaccine (D–42), before the second dose (D–21), before oral inoculation with 10echnique .Salmonella Typhimurium in feces and/or organ samples was possible in all 40 inoculated piglets. In four animals from G1 and two animals from G2, there was no detection of Salmonella in feces, but the bacteria were isolated in the organ samples of these animals. On the other hand, although Salmonella was detected in the feces of one animal from G2, there was no detection of bacteria in its organs.Successful microbiological isolation of Salmonella isolated in feces and/or organs of experimentally infected animals showed identical patterns of susceptibility to the tested antimicrobials.Furthermore, the strain used in preparation of the inoculum and 8 CFU of Salmonella Typhimurium.The main necroscopic findings in animals in both groups were the presence of button-shaped ulcers in ileocecal region  and hyperplasia of lymphoid tissue in colon  after oral inoculation with 10Salmonella Typhimurium during the evaluation period, with a significant difference in D3 (G1: 35.0% and G2: 70.0%). Of the 220 rectal swabs analyzed in each experimental group, it was possible to perform the microbiological isolation of Salmonella Typhimurium in 42 samples from animals of G1 (19.1%) and 70 samples from animals of G2 (31.8%), with a significant difference between groups (p < 0.05)  . It was xcretion .Salmonella Typhimurium was performed in 17 samples from animals of G1  and 41 samples from animals of G2 , with a significant difference between the groups (p < 0.05)  .Salmonella Typhimurium between the two groups at the evaluated times. Microbiological isolation of Salmonella Typhimurium was successful in all evaluated organs, except in the spleen. There were 45 positive samples from animals in G1  and 54 positive samples in animals from G2 , the antigens used as coating, and the isotype of immunoglobulin used as the conjugated secondary antibody . Similard effect  because d effect . In thisimmunity . TherefoSalmonella-infected pigs may be associated with stress. Nonetheless, body temperature of most animals may also be influenced by environmental conditions such as room temperature, which in our study ranged from 18.4 °C to 28.6 °C.An increase in temperature in response to a bacterial challenge is common since febrile state enhances the bacteria-killing efficacy of the immune system; however, in the present study, none of the animals presented a rectal temperature higher than 39 °C, which is the acceptable temperature for the pig’s age . AdditioRegarding the hematological findings, small numeric variations were reported in this study; however, none of them were of significance once the results were within the normal parameters for swine . MoreoveSalmonella vaccination in pigs, especially regarding its fecal excretion over time. Nonetheless, vaccines against Salmonella in swine intend to prevent the colonization and shedding of the pathogen and the development of subclinical or clinical disease [Hence, the results from this study reinforce the importance of  disease ; even th disease . Additio disease . Therefo disease ,41.Salmonella infections in pigs must be considered of concern for two main reasons: the first is the clinical disease, and the second is the food-borne disease, which represents a threat to human health. Furthermore, given that pork meat is one of the most consumed animal proteins in the world, and that non-typhoid Salmonella infection in pigs is the main source of carcass contamination at slaughter, alternatives such as vaccination are increasingly important in controlling the disease and in decreasing excretion of the pathogen along the production chain. Finally, Salmonella infection in pig production animals is a rising concern worldwide since pork products are commonly associated with human salmonellosis outbreaks. Furthermore, it is known that cross-contamination of pork can be reduced by controlling the disease in pig farms, especially through the use of vaccines. Thus, our results demonstrate that vaccination of pigs with Salmonella Choleraesuis and Salmonella Typhimurium bacterin partially protected the animals against experimental Salmonella Typhimurium infection, reducing the excretion of bacterium in feces and colonization of organs of vaccinated animals. Although the results show some protection against the infection, further studies are needed. Still, our findings should be extrapolated to field conditions with care because there were some limitations regarding the number of animals in the sample and the specificity of serological tests.


Conclusions: A correct preoperative diagnosis of colonic lipoma causing intussusception might not be easy. Despite nonspecific clinical and laboratory presentation, cross-sectional imaging can help differential diagnosis. Surgical treatment depends on the localization.Background: Colonic lipomas are rare and can sometimes cause intussusception. The aim of this review was to define the presentation and possible management for colocolic intussusception caused by colonic lipomas. Methods: A systematic search for patients with colocolic intussusception caused by colonic lipoma, including all available reports up to 2021. Epidemiological, clinical, laboratory, and instrumental data and details about the treatments performed were gathered. Results: Colocolic intussusception caused by lipoma is more frequent in women (57%), occurring between 40 and 70 years of age. Up to 83% of patients report abdominal pain, followed by constipation (18%), rectal bleeding (16%), and diarrhea (12%), with abdominal tenderness (37%), and distension in 16%, whereas 24% have a negative exploration. CT (72%) and colonoscopy (62%) are more commonly able to diagnose the entity. The most common location of intussusception is the transverse colon (28%). The surgical operation varies according to the site. The average dimensions of the lipoma are 59.81 × 47.84 × 38.9 mm Lipomas are nonepithelial benign adipose tumors observed throughout the gastrointestinal tract, most frequently located in the colon . GeneralIn the majority of cases, lipomas are asymptomatic, with the diagnosis being made incidentally during colonoscopy, surgery, or autopsy . HoweverIntestinal intussusception is the invagination of an intestinal loop with a mesenteric fold (intussusceptum) in the lumen of a continuous portion of the intestine (intussuscipiens) following peristalsis . HoweverAlthough abdominal computed tomography (CT) has proved useful in diagnosing intussusception in 72% of cases ,9, it haThe aim of this study was to define the reported distribution of colonic lipomas, which are the cause of colonic intussusception, in order to identify the best diagnostic and therapeutic procedure for the condition.A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed databases were searched using the date range of January 1900 to June 2021. The key words searched were “colonic” AND “lipoma” AND “intussusception”. One reviewer (FMT) reviewed all the records by title and abstract, followed by a review of the full-text article for those that met the screening criteria. The patient observed by the authors of the current manuscript gave written informed consent for publication.Inclusion criteria consisted of colonic intussusception caused by lipoma and treated by endoscopic or surgical intervention. Reports of randomized controlled trials, cohort studies, case–control studies, and case series were included. No language restrictions were applied. Items in which patients were not of adult age were excluded. Items in which the diagnosis of intussusception was not lipoma were excluded.All articles selected for full-text review were examined by the reviewer (FMT), who decided on inclusion or exclusion and the extraction of the study data. For the purpose of this review, the colonic lipoma was classified by localization along the colon , by size, and by histological finding. Colonic intussusception was then classified by signs and symptoms, laboratory tests, radiological exams, and the type of intervention . Information regarding the demographic characteristics of the study subjects, the position of lead points, patient symptoms and physical examinations, laboratory findings, diagnostic methods, operative methods, hospital lengths of stay, and dimensions of the tumor was extracted from each study report and tabulated in Microsoft Excel.A single weight-adjusted mean or proportion for each variable or outcome was computed for each item.A total of 144 full-text articles were included, out of 263 records . All 144The authors observed a case of colonic lipoma causing intussusception. The data of the patients were pooled in the review. The patient had been reporting diffuse and intermittent abdominal pain for one year. An ultrasound scan was performed, and it showed only biliary sludge. The patient began medical therapy for which she showed improvement. A worsening of the clinical condition in the following two months, associated with the onset of diarrhea, led the patient to be reevaluated for her condition. In this case, a CT scan was performed .Given the presence of intussusception, with initial signs of the ischemic suffering of the bowel , immediaAt surgery, a long colocolic intussusception, with its distal end at the hepatic flexure, was confirmed, and an ileocolic resection and side-to-side anastomosis were performed. The pathology was consistent with a large solitary exophytic mass in the ascending colon, with a uniform yellow cut surface .The lesion was well-circumscribed, but unencapsulated, involving the submucosa, and measuring 6 cm in its maximum diameter. The overlying mucosa appeared to be intact, with a smooth surface. Upon microscopic examination, a nodular submucosal tumor composed of mature adipocytes, and covered by substantially unaltered mucosa, was seen. The lesion showed extension towards the muscularis propria with pushing borders. Neither cellular atypia nor infiltrative growth were found . These fData were available from 162 patients. The median age of patients was 52 (19–88) years, and 72% of patients presenting with colocolic intussusception from colonic lipoma ranged between 40 and 70 years. Men (70) represented 43% of the cases analyzed and women (92) represented 57%.Data on reported symptoms and physical explorations were available from 161 and 123 patients, respectively.The most common symptom reported by patients with colocolic intussusception was abdominal pain (83%), described in 29% of cases as intermittent, and in 17% of cases as crampy. Patients reported that symptoms were related to bowel habits, in particular, constipation (18%), or diarrhea (12%), which in some cases is watery or bloody, or alterations in the bowel movements. Low gastrointestinal bleeding occurred in 16% as rectal bleeding, in 4% as rectal bleeding associated with mucus loss, and in 11% as hematochezia. More nonspecific symptoms, such as nausea, vomiting, weight loss, bloating, and fever occurred in 9, 14, 11, 3, and 2%, respectively. Partial obstruction and obstruction occurred in 4% and 7% of cases, respectively. Patients also reported tenesmus (3%) and dyspepsia (1%). All data are shown in The most frequent clinical sign was tenderness (37%), followed by abdominal distension (16%). Depending on the location of the lipoma, a palpable abdominal mass (16%), a prolapsing mass through the rectum (11%), or a rectal mass (2%) was detected. Voluntary guarding was reported in 4% of cases, while rebound tenderness occurred in 2% of cases. A normal abdomen was found in 24% of cases. The data are shown in Laboratory data were available from 65 cases. Laboratory tests were normal in 61% of cases, WBC were high in 16%, and CRP in 8%. Anemia was present in 14% of the subjects included in the study.The instrumental methods used for the identification of colocolic intussusception underlying a colonic lipoma were ultrasound, abdominal X-ray, barium-enema, CT, and colonoscopy. These methods were used in 18, 18, 27, 72, and 62% of cases (based on 156 cases), respectively. 1% of the patients examined did not undergo any preoperative instrumental examination, 28% underwent only one imaging evaluation, 48% underwent two different methods, while the remaining 24% of patients underwent three (19%), four (3%), or five (2%) different tests.3, with a minimum of 15 × 15 × 15 mm3, and a maximum of 160 × 110 × 100 mm3.The colonic lipoma causing colocolic intussusception was localized more frequently at the transverse colon (28%), followed by the sigmoid (20%), the cecum (19%), the ascending colon (15%), the descending colon (14%), and the rectum (4%) . The aveTreatment can be performed endoscopically, laparoscopically, or with an open technique. The types of interventions included: endoscopic (10%) or open (8%) polypectomy; right colectomy (32%); extended right colectomy (4%); segmental colectomy (20%); left colectomy (13%); sigmoidectomy (10%); Hartmann sigmoidectomy (1%), and anterior rectal resection (3%). Both open and laparoscopic approaches were used.The average length of hospital stay was 6.24 (2–18) days.Colonic lipoma was first described by Bauer in 1757 ,13. SincWomen (57%) are more frequently affected than men (43%), even in the case of symptomatic lipoma ,15. EvenGenerally, only 25% of colonic lipoma patients develop symptoms. On the other hand, when a giant lipoma is present, patients who have symptoms reach 75% of cases ,17.The main clinical manifestation associated with colocolic intussusception from colonic lipoma appears to be abdominal pain, present in up to 83% of cases. In patients suffering from abdominal pain, 29% of them complain of intermittent pain, while 17% describe a cramp-like pain. Other symptoms often identified by the patients are changes in the bowel habits, in particular: constipation (18%), diarrhea (12%), and, more generally, a change in the bowel movements (8%). There may also be blood (16%) or mucous/blood (4%) losses from the rectum while, on some occasions, gastrointestinal bleeding is limited to less important manifestations, such as hematochezia (11%). The subjects examined also complained of general complaints, such as nausea (9%), vomiting (14%), and weight loss (11%). Depending on the position of the lipoma, the patient may complain of tenesmus (3%), bloating (3%), and up to partial (4%) or complete bowel obstruction (7%).During physical examination, abdominal tenderness (37%) was the most detected sign, followed by abdominal distension. Surprisingly, 24% of patients, despite an underlying symptomatology, present a completely normal abdomen at physical examination.In most cases, in patients who came to the hospital for lipoma-induced intussusception, laboratory tests were normal (61%); however, variations in inflammatory indices may be found. Another 14% of patients eventually have anemia.The clinical presentation of the patient is, therefore, quite vague, and this, together with a nonspecific physical examination and a nonspecific laboratory picture, makes preoperative diagnosis difficult ,19.Ultrasound appears to be a rapid and minimally invasive method, which represents the first imaging approach performed by an experienced and skilled operator . The preAbdominal X-ray is a first-level investigation , used inThe most used method is the barium-enema study 27%), a method used both for the diagnostic capacity [%, a methHowever, the most used instrumental tests are CT of the abdomen (72%) and colonoscopy (62%).CT imaging, having a sensitivity of 71–87%, and a specificity of up to 100% ,29, makeHowever, particular attention must be paid in making the diagnosis because, in any case, 60–65% of cases of intussusception of the large intestine are underlying malignant lesions .Colonoscopy allows for direct vision of the lesion and biopsies. As in the case of CT, there are pathognomonic signs for lipoma, i.e., the “pillow mark” , and the “bare fat mark” (leakage of fat after biopsy) ,33.Magnetic resonance imaging is very effective in highlighting adipose lesions because of the peculiar characteristics of the signal intensity of this tissue, especially T1-weighted and fat-suppressed images. However, this type of imaging is rarely used to detect and study intestinal neoplastic lesions . In studMore than 70% of patients require at least two instrumental investigations before having a diagnosis of intestinal intussusception caused by a lipoma.The use of different diagnostic techniques depended on the period studied: the barium-enema study, which represented the main instrumental examination performed before 2000, is currently not used (44% pre-2000 vs. 15% post-2000) and has been replaced by computer tomographic examination and the endoscopic exploration of the bowel.The most conservative option, in cases of certainty of the benign nature of the lesion, involves the simple removal of the lipoma. This procedure can be performed both endoscopically  and surgically (8%). In the first case, different techniques are possible, such as the “unroofing” dissection of the lipoma with a loop-assisted snare, the “Ligate and Let Go” technique, the endoscopic mucosal resection (EMR), and the endoscopic submucosal dissection (ESD), all with excellent remission rates ,36. In tIf there is no certain preoperative diagnosis of colon lipoma, or localization of the lipoma and state of the invaginated bowel ,38, boweThe length of hospitalization does not usually exceed one week, depending on the type of approach used and perioperative complications.Lipomas causing colocolic intussusception are, in most cases (88%), giant lipomas. In almost all cases, the lipomas examined are submucosal and, in minimal part, subserosal, or belonging to the muscularis propria.Surgery is currently the most commonly used therapeutic option in intussusception caused by lipoma and, more generally, in adult colonic intussusception. Making a preoperative diagnosis of colonic lipoma causing intussusception is somewhat complex. However, despite the nonspecific clinical-laboratory picture, clinical-instrumental integration can allow a diagnosis to be made, which will still need to be confirmed histologically. In fact, methods have not been developed with sensitivity and specificity such as to guarantee, in all cases, a simple enucleation of the lipoma or minimal resections, without the risk of a malignant diagnosis.


Aloysia triphylla; Lippia citriodora) is often used as a spice in tea or beverages. Its leaves are rich in polyphenols, which have antioxidant and anti-inflammatory bioactivities. In the present study, we investigated whether supplementation with Planox® lemon verbena extract (LVE) could improve muscle damage and biochemical indicators after exhaustive exercise challenge. All subjects  underwent a double-blind trial and were randomly divided into a placebo group (0 mg/human/day) and an LVE supplement group (400 mg/human/day), with gender-equal distribution. All subjects started supplementation 10 days before exhaustive exercise and continued it until all tests were completed. Before the intervention, after the exhaustive exercise, and on the following 3 days, the participants underwent 12-minute Cooper running/walking; blood collection; assessments of pain, muscle stiffness, maximum jump heights, and isometric maximum muscle strength. The results showed that supplementation with LVE effectively increased GPx and reduced CK, IL-6, 8-OHdG and muscle pain after the exhaustive exercise, but it had significant effect on strength recovery. In summary, LVE is a safe and edible natural plant extract that can reduce muscle damage and soreness after exercise. This trial was registered at clinicaltrials.gov as NCT04742244.Excessive exercise load can cause muscle soreness and fatigue, as well as inflammation and oxidative stress. Lemon verbena ( Whether one is an untrained or a highly-trained athlete, excessive or unaccustomed exercise can cause the ultrastructural destruction of skeletal muscle fibers, called exercise-induced muscle injury (EIMD) The DOMS and EIMD caused by exercise can be evaluated from biomechanical indicators, such as reduced maximal isometric contraction or range of motion (ROM) Many studies have tried to examine several interventions such as massage A. citrodora), synonyms: Aloysia triphylla; Lippia triphylla; Verbena triphylla, is a perennial subshrub, a species of flowering plant in the verbena family Verbenaceae, which is native to South America. It is mainly used in tea, beverages, food, and spices. In the past, it was usually used for gastrointestinal and nervous system diseases in traditional medicine in vivo and in vitro tests Lemon verbena . Before the experiment, the researchers explained the experimental process in detail, and the experiment began after the subjects signed the consent form.Figure 1. Before the intervention, all subjects performed endurance exercise, biomechanics, basic biochemical values, and body composition tests. After all subjects received placebo or LVE supplementation for 10 days, they immediately performed exercise endurance challenges and muscle exhaustive exercise after be asked fasting 8 hours. Then at 3, 24, 48, and 72 hours after the exhaustive exercise, all subjects were again subjected to various biomechanical and blood biochemical tests to observe the effects and changes at different time points.Before the intervention, 30 male and 30 female subjects underwent a double-blind trial and were randomly divided into two groups with gender-equal distribution: a placebo (0 mg/day) group  and an LVE (400 mg/day) group . The experimental process is shown in acteoside and isoactoside, which were determined by a high-performance liquid chromatography (HPLC) method . As shown on Figure 2, The retention time of acteoside and isoactoside in LVE was 6.10 and 9.12 min, respectively.The supplement in this study was a commercial product Planox® lemon verbena extract (LVE) , which is obtained by ethanol extraction from organic dried lemon verbena leaves without any additives, and standardized to 9% Both LVE and placebo were made into capsules of matching size and color, provided by Hänseler AG . Each capsule contained 200 mg of lemon verbena extract or placebo . All subjects were instructed to take two capsules every morning. The product was consumed for the 10 days preceding the exhaustive exercise test, on the day of the test, and for 3 days after the test.The method of muscle damage caused by the maximum eccentric load of the lower extremity was based on past research, with appropriate modifications The 12-minute Cooper running/walking test is used as an initial simple method to assess aerobic endurance and physical fitness The CMJ test is a practical, effective, reliable, and simple method of measuring lower limb strength, which is related to the maximum speed, strength and explosive force of the lower limbs. For this test, participants stood on the Kistler force measurement platform  on both feet and performed to inspection. During the test, they were asked to put their hands on their hips and remain on the platform. After that, they were asked to squat down until the knees bent 90 degrees and then to immediately jump as high as possible. The average power (MF), peak power (Fpeak), flight time (FT) and strength development speed (30 ms) were recorded during the jump. Each participant repeated the test 3 times, and CMJ data were obtained at the designated points. The instrument was calibrated for each individual's weight The IMTP is a force-time diagnostic tool A handheld MyotonPRO  device was applied to measure the viscoelastic and stiffness response of the muscle to a brief (15 ms) mechanical impulse  on the skin surface above the muscle. It is the biomechanical property of a muscle that resists either contraction or an external force, tending to deform its initial shape. The probe of MyotonPRO, placed perpendicular to the skin surface overlying tested muscle, produces a short mechanical impulse. Naturally damped oscillations due to the response of soft tissue are then processed by the device. The inner and outer femoral muscles of the thigh were tested at the midpoint of the muscle. In this study, five measurements were taken and the average value was used. During the MyotonPRO measurement, under the guidance of the researcher, the participants were asked to lie supine on the bed and to relax their muscles For the pain assessment, the subjects were asked to sit on a chair or to stand up from a chair and to assess the pain they experienced during the process on a 100 mm visual analog scale (VAS) ranging from 0 mm (no pain) to 100 mm (worst imaginable pain). This assessment was performed before and 3, 24, 48, and 72 h after the exhaustive exercise program.We used the InBody 570 , the bioelectrical impedance analyzer (BIA) to measure body composition. The device can screen frequencies of 1, 5, 50, 260, 500 and 1000 kHz within 60 seconds. After cleaning the palms and soles of the feet, the subject stood vertically on the electrodes of the instrument, holding the sensing handle with both hands and keeping the arms away from the body at a 30° angle, and avoided talking or moving during the measurement To understand the subject's metabolism and health before the intervention, we collected blood from a venous catheter in the arm for analysis at the beginning of the experiment. The physiological adaptations and clinical biochemistry of the blood serum were assessed with an autoanalyzer  for glucose, aspartate transaminase (AST), aminotransferase (ALT), LDH, total cholesterol (TC), triglyceride (TG), high-density lipid-cholesterol (HDL-C), and low-density lipid-cholesterol (LDL-C) levels.CK is a biomarker of muscle damage and usually increases after strenuous exercise Exercise training would generate oxidative stress and regulate the endogenous antioxidant defense system (including GPx) IL-6 is a multifunctional cytokine involved in pro-inflammatory and anti-inflammatory processes For the urinary 8-OHdG measurement, urine samples were collected at 24 hours after the muscle exhaustive exercise, and frozen immediately at the survey site and stored at -20°C until analysis. 8-OHdG was measured by enzyme-linked immunosorbent assay (ELISA) using a commercial analysis kit .p < 0.05.All the data are expressed as mean ± SEM. Statistical analyses were performed in SAS 9.0 . Multi-group comparisons were analyzed by one-way analysis of variance (ANOVA), and within-group differences (before vs. after LVE supplementation), by paired Student's t-test. Statistical significance was set at Table 1 presents the basic information of the subjects and the biochemical values of basal metabolism. The average ages of the subjects in the placebo and LVE supplement groups were similar, 22.1 and 22.3 years old, respectively. The average heights were also quite close. In terms of metabolism, blood biochemical values including glucose, TC, TG, HDL, LDL and other indicators had no significant differences between the two groups, all falling within the normal healthy range.Figure , the placebo group and the LVE supplement group were tested for endurance with a 12-minute Cooper running/walking test pre- and post-intervention, and there was no significant difference in running distance between the two groups. However, after comparing the changes in the values of the two groups between pre- and post-intervention , we found that the running distance changes in the placebo group and the LVE supplement group at the 3rd, 6th, 9th, and 12th min were -4 ± 14 and 1 ± 12 m, 6 ± 11 and 45 ± 13 m, 5 ± 20 and 72 ± 25 m, and -8 ± 17 and 132 ± 29 m, respectively. Compared with those in the placebo group, the improvements in the LVE group were significantly higher at the 6th min (p = 0.0257), 9th min (p = 0.0393) and 12th min (p = 0.0001). In the within-subject pre- and post-intervention comparison, only in the LVE supplement group was there significant improvement at the 6th (p = 0.0257), 9th (p = 0.0257) and 12th (p = 0.0257) minutes.As shown in Table 2 shows that muscle tension in the medial quadriceps muscle was less affected by exhaustive exercise but that it increased with time in the lateral quadriceps muscle. In both the medial and lateral quadriceps at 48 hours after the exhaustive exercise, muscle tension was significantly higher in the placebo group than in the LVE group (p < 0.05). Only 3 hours after the exhaustive exercise, the muscle stiffness in the medial and lateral quadriceps was significantly greater in the placebo group than in the LVE group. However, supplementing with LVE had no significant effect on muscle elasticity.The effect of exhaustive exercise on muscle soreness was measured with objective instruments for determining muscle tension, stiffness and elasticity, and recorded with a subjective perception scale by VAS. We analyzed two important muscle groups, the medial and lateral quadriceps. Table 3), the muscle pain appearing within 48 and 72 hours after the excessive exercise of the medial quadriceps muscle was significantly lower in the LVE group than in the placebo group. In the lateral quadriceps muscle, muscle pain was significantly lower in the LVE group than in the placebo group at 24, 48, and 72 hours after the exhaustive exercise.In the VAS evaluation .After the exhaustive exercise, the isometric maximum muscle strength recovery effect was better in the LVE group than in the placebo group, but still less pronounced , 21.44% (p = 0.0288) and 21.58% (p = 0.0271), respectively.The change in the CK value of muscle injury induced by exhaustive exercise is shown in p = 0.0053). In addition, in terms of within-subject comparisons, the serum IL-6 level of the placebo group significantly increased at 3 (p < 0.0001) and 48 (p = 0.0021) hours after the exercise relative to the baseline (pre-exercise). In contrast, the serum IL-6 level of the LVE group was significantly higher than the baseline only at 3 hours after the exercise (p = 0.0002) .Before the exhaustive exercise, there was no significant difference in serum IL-6 between the placebo group and the LVE group. At 48 hours after the exercise, the serum IL-6 level was significantly higher in the placebo group than in the LVE group (p = 0.0446) and 48 (p = 0.0300) hours after the exercise. In addition, in the within-group comparisons, the placebo (p = 0.0167) and the LVE (p = 0.0047) groups only had significant differences before and 3 hours after the exercise .Although there was no significant difference in GPx between groups before the exercise, it decreased slightly and then recovered after the exercise. However, GPx was still significantly higher in the supplementary LVE group than in the placebo group at 3 , respectively. The level was significantly lower in the LVE group  than in the placebo group.8-OHdG in urine is often used as an indicator of deoxyribonucleic acid (DNA) damage caused by oxidative stress. In this study, subjects' urine was collected 24 hours after the exhaustive exercise for analysis. As shown on Table 6).In the blood biochemical, serum glucose, AST, ALT and LDH in the different time point were no significantly between placebo and LVE group, respectively .Many previous studies have used polyphenols as acute and non-acute sports nutrition supplements. They have antioxidant and anti-inflammatory effects, and they eliminate reactive oxygen species (ROS) produced after exercise, which may be one of the factors that improve exercise performance [34)]. In addition, both acute and chronic supplementation of polyphenols can improve vascular function, especially endothelium-dependent vasodilation. Endothelial-dependent vasodilation is nitric oxide (NO)-dependent. The main mechanism of NO is to inhibit the vasoconstriction of adrenaline through direct vasodilation of vascular smooth muscle cells and increased muscle implantation Figure 4) and IL-6  after the exercise and led to better recovery.CK is a dimeric protein with an enzyme that can catalyze the transfer of high-energy phosphate from ATP to creatine, and it is important in maintaining cell energy and muscle cell metabolism. It mainly exists in the heart muscle and is rare in other tissues, such as skeletal muscle. CK is the main isoenzyme in skeletal muscle; it binds to the M-line structure of muscle tissue in myofibrils. In normal serum, the total CK level mainly comes from skeletal muscle Figure 6) had lower oxidative damage.It is well known that acute exhaustive exercise will increase the production of ROS, blood oxidative stress and total oxidant biomarkers, and that this production increases with greater exercise time and exercise intensity 2O2 detoxification has for a long time been considered to be GPx 2O2, GPX competed with catalase for H2O2 as a substrate, but catalase had much lower affinity for H2O2 than GPX Figure , although GPx activity decreased after the exercise and then recovered, compared with the placebo group, the LVE supplement group had better antioxidant capacity.Previously study had pointed out that strenuous exercise could increase free radicals in skeletal muscles, caused GSH oxidation, and released lysozymes and other signals that damage cells Muscle soreness peaks 24 hours or 48 hours after injury exercise In this study, one limitation was that it was necessary to guarantee subjects returned to the laboratory for various tests at 3, 24, 48, and 72 hours after the exhaustive exercise. Therefore, out of 98 subjects who met the criteria, only 69 who agreed to participate on time were recruited. Of these, 9 subjects withdrew due to temporary conditions, and in the end, 60 subjects completed the study. Whether physiological factors have impacts on the outcomes examined in this experiment needs to be further determined.In conclusion, the current study supplementation with lemon verbena extract containing polyphenols for 10 days effectively reduced muscle damage and oxidative stress after exhaustive exercise. The benefits on strength recovery need to be further explored. In addition, LVE increased antioxidant activity and reduced pain and muscle stiffness.


Moreover, SaNP treatment followed by alternating magnetic field exposure significantly improved the survival rate of treated mice compared to the controls. The median survival time was 29 ± 3.8 days in the treated group vs. 21.6 ± 4.9 days in the control, p-value 0.029. These assessments open new avenues for generating SaNPs and alternating magnetic field application as a potential novel therapeutic modality for metastatic cancer patients.Sarah Nanoparticles (SaNPs) are unique multicore iron oxide-based nanoparticles, developed for the treatment of advanced cancer, following standard care, through the selective delivery of thermal energy to malignant cells upon exposure to an alternating magnetic field. For their therapeutic effect, SaNPs need to accumulate in the tumor. Since the potential accumulation and associated toxicity in normal tissues are an important risk consideration, biodistribution and toxicity were assessed in naïve BALB/c mice. Therapeutic efficacy and the effect on survival were investigated in the 4T1 murine model of metastatic breast cancer. Toxicity evaluation at various timepoints did not reveal any abnormal clinical signs, evidence of alterations in organ function, nor histopathologic adverse target organ toxicity, even after a follow up period of 25 weeks, confirming the safety of SaNP use. The biodistribution evaluation, following SaNP administration, indicated that SaNPs accumulate mainly in the liver and spleen. A comprehensive pharmacokinetics evaluation, demonstrated that the total percentage of SaNPs that accumulated in the blood and vital organs was ~78%, 46%, and 36% after 4, 13, and 25 weeks, respectively, suggesting a time-dependent clearance from the body. Efficacy studies in mice bearing 4T1 metastatic tumors revealed a 49.6% and 70% reduction in the number of lung metastases and their relative size, respectively, in treated  Cancer is a major public health problem worldwide and is the leading cause of death in the Western world with a resultant significant detrimental economic impact . CurrentA variety of nanoparticles have been investigated as drug carriers, photothermal agents, contrast agents, and radiosensitizers . Of partPhysiologically, elevated body temperature can damage and kill cancer cells with minimal injury to normal cells, thereby providing a therapeutic index which can be exploited. Hyperthermia, the process of raising the temperature of tumor-loaded tissue to 40-43°C results in the denaturation of proteins and structural damage within cancer cells .We have developed a novel nanoparticle-based treatment termed Sarah Nanotechnology system that selectively destroys cancer cells by hyperthermia. Sarah Nanotechnology comprises of: (i) Sarah Nanoparticles (SaNPs), containing encapsulated iron oxide (IO) nanoparticles, that attach to cancer cells, and an (ii) electromagnetic induction system (EIS) that generates an alternating current magnetic field (AMF) that is converted to heat by the SaNPs due to their magnetic properties. The applied AMF heats the SaNPs to a predefined and controllable temperature, thereby offering an innovative approach to treat cancer by inducing non-ablative thermic damage .SaNP consists of 25 nm IO nanoparticles, a phase change material (PCM) core, and an encapsulating hydrophilic polymer comprised of amine functionalized 6-arm-branched polyethylene glycol (PEG) 20,000, that enables flexibility, increases biocompatibility, and significantly masks the SaNP from the body’s mononuclear phagocyte system (MPS) thereby reducing uptake by phagocytic cells . These pSaNPs are intravenously (IV) administered to the patient and localize on cancer cells. They accumulate on cancer tissue at higher concentrations compared to normal tissue mainly due to the enhanced permeability and retention (EPR) effect, a central mechanism for passive tumor targeting, which allows extravasation of the nanoparticles and enables the preferential retention of SaNPs in tumors due to their leaky vasculature and reduced lymphatic drainage , 10.Following delivery and attachment of the SaNPs to the malignant cells, the patient undergoes regional 290 ± 10% kHz AMF application with the EIS generating a magnetic field at a range of 8-33 kA/m, the SaNPs subsequently convert the applied AMF to latent heat and retain it, and the PCM core controls and stabilizes the SaNP temperature to 50 ± 3°C, thereby using this heat to cause hyperthermic cancer cell death without harming healthy cells under a magnetic field. The main innovation of the SaNP lies in its inherent ability to control its temperature without inducing thermal ablation which occurs at temperatures above 60°C  was purchased from Sigma Aldrich, Rehovot, Israel.Hank’s Balanced Salt Solution (HBSS), Fetal Bovine Serum (FBS), RPMI 1640 medium, 0.25% Trypsin-EDTA solution, sodium pyruvate, glutamine, and antibiotics  were all from Biological Industries, Beit-Haemek, Israel. Puromycin was from Santa Cruz Biotechnology, Inc., TX, USA.Amine functionalized 6-arm-branched, polyethylene glycol (PEG), 20 kDa molecular weight, was purchased from SunBio, South Korea. Water for injection (WFI) was from B. Braun Medical Inc., PA, USA.SaNPs were characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM) imaging to determine their physicochemical parameters and morphology.Hydrodynamic size, size distribution, and zeta potential measurements were conducted using a Zetasizer Nano Series ZS  operating with a 4 mW HeNe laser (632.8 nm), a detector positioned at a scattering angle of 173°, and a temperature-controlled jacket for the cuvette. Three measurements consisting of up to 12 consecutive sub-runs were performed for each sample. Dynamic correlation functions were fitted by a second-order cumulant method to obtain the size distributions. For the zeta potential measurements, 0.8 mL of the SaNP dispersion were loaded into folded capillary zeta potential cells with integrated gold electrodes. Three measurements consisting of 12 sub-runs were performed at 25°C.Samples for TEM were prepared by spreading 5 µl of the SaNP dispersion onto the surface of a 400-mesh carbon-coated copper grid . Uranyl acetate was used as the staining agent. The samples were air-dried at room temperature, and low-resolution TEM images were obtained using a Tecnai G2Spirit Twin T-12 electron microscope .2 at 37°C.The 4T1 mouse mammary carcinoma cell line was obtained from the American Type Culture Collection . Cells were grown in RPMI 1640 medium supplemented with 10% (v/v) FBS, 1.0 mM sodium pyruvate, 100 U/mL penicillin, and 100 μg/mL streptomycin. Cells were maintained in a humidified atmosphere containing 5% COFor imaging purposes, modified human embryonic kidney GP2-293 cells were co-transfected with pRetroQ-mCherry-N1 Vector using the complementary Retro-X™ Universal system  to generate mCherry containing viral particles. pRetroQ-mCherry-N1 retroviral particles containing supernatant were collected 48hrs after transfection. 4T1 cells were infected and mCherry positive cells were selected by Puromycin (2µg/mL) resistance.4 cells/200μl solution. The cell suspension was IV injected via the lateral tail vein of BALB/c mice.To generate a metastatic lung cancer model, mouse 4T1 mCherry breast cancer cells were grown to 70% confluency and metastatic tumors were established by harvesting early passage 4T1 cells with 0.25% Trypsin-EDTA, centrifuged at 500×g for 5 min, and resuspended in ice cold HBSS at 2.5×10ad libitum and allowed free access to drinking water. The temperature and relative humidity were kept constant at 20-24°C and 60%, respectively. The health status of the animals used in the experiments was examined on arrival. Only animals in good health were acclimatized to laboratory conditions for 7 days prior to each study initiation.BALB/c mice, 7-8 weeks old, were purchased from Envigo . All animal experiments were reviewed and approved by an Institutional Animal Care and Use Committee (IACUC), followed officially approved procedures for the care and use of laboratory animals, and all protocols met the requirements of the local ethical committee of Bar Ilan University, Israel. The mice were fed Animals were monitored and observed for the total duration of the experiments. Viability checks for mortality and morbidity were performed at least once daily whereas detailed clinical signs were performed twice a week. Clinical signs observations included changes in skin, fur, eyes, mucous membranes, occurrence of secretions and excretions  and autonomic activity . Changes in gait, posture and response to handling, as well as the presence of bizarre behavior, tremors, convulsions, sleep and coma were also observed and recorded. All animals were humanely euthanized at the end of the experiments.SaNPs at concentrations between 1.6-2.1 mg IO/mL were supplied as a dispersion in water for injection (WFI) and administered to the mice via an IV bolus injection to the lateral tail vein. The volume of the injection was decided after weighing each mouse, 10 µl NP per 1 gr of mouse, which is the maximal feasible dose in mice. All test materials were injected using an insulin syringe and a 27G needle.Alternating current magnetic field (AMF) application was conducted using an electromagnetic induction system (EIS) comprising of 3 main components: an electromagnetic coil, an AMF generator, and a chiller. The EIS generated a magnetic field at an amplitude range of 8-33 kA/m. A polypropylene perforated housing 50-mL tube was used to hold the mouse, without anesthesia, while in the system’s inductor coil. This tube provided shield so that the mouse could not come in direct contact with the coil and kept all mice positioned in the same direction. Each mouse was inserted into the housing tube, which was then placed in the coil. The coil was powered by the generator and cooled by running water kept at 20°C by the chiller . AMF application commenced 2-8hrs post SaNP administration. Upon activation of the AMF at 290 ± 10% kHz, the mice were irradiated for a total of 30 min.The short-term biodistribution of SaNPs in the target organ (lungs) and blood over time, was assessed at 3 different timepoints, 2, 4, and 8hrs, following a single IV bolus injection of SaNPs (2.1 mg IO/mL) to the tail vein of 12 BALB/c female mice bearing 4T1 breast cancer metastatic tumors to determine the optimal time for AMF exposure. Five mice were weighed and assigned to each group. At termination time the lungs from each mouse were excised, weighed and stored frozen separately. Blood was collected in EDTA-tubes , the volumes were measured and recorded, and samples were stored at 4°C until analysis.The IO content in the lungs and blood was determined in the specimens by superconducting quantum interference device (SQUID) analysis that measures the magnetic properties of nanoparticles and enables detection in organic samples with high sensitivity . This meThe long-term biodistribution and excretion of SaNP in vital organs and blood was evaluated over time. Twenty healthy BALB/c female and male mice were weighed and treated with Sarah Nanotechnology comprising of a single SaNP IV injection (1.7 mg IO/mL), followed by 30 min of AMF application (16.7 kA/m) at 8hrs post injection to examine the SaNPs’ fate within the context of the whole approach . Each group was assigned 10 animals, 5 male and 5 female mice. The animals were sacrificed at 4 and 13 weeks post a single treatment. All animals were subjected to blood sampling and organ harvesting at their respective scheduled termination. A volume of at least 300 μl whole blood, collected into lithium heparin-coated tubes  was individually obtained from the mice. Blood samples were refrigerated (2-8°C) until all organs were processed following termination.Organ collection included the following: brain, spleen, kidneys, lungs, heart, liver, mandibular and medial iliac lymph nodes, all weighed wet as soon as possible following their dissection and individually fixed in pre-labeled tubes containing 10% neutral buffered formalin (NBF). The fixed organs were cut into several sections using disposable equipment, to avoid cross-contamination. The processing of the organs was done separately for each follow up period. Each section was individually placed in a pre-weighed tube, containing the organ section, and weighed again. The samples were analyzed for the quantitation of IO content by particle electron paramagnetic resonance (pEPR), using a pEPR analyzer. The pEPR technique has been validated, is based on a low-field and low-frequency electron paramagnetic resonance, measures the magnetization of super paramagnetic iron oxide nanoparticles (SPIONs), and enables their quantitation . The bioThe potential toxic effects of SaNPs were assessed following a single IV bolus injection (2.1 mg IO/mL) to BALB/c healthy mice followed by AMF application (33 kA/m), to examine the toxicity of the full treatment. Thirty mice were subjected to observation and terminated at 3 different timepoints, 3, 14, and 30 days after treatment, control mice remained untreated. Five mice were weighed and assigned to each group.A separate repeated dose chronic toxicity study was conducted in female BALB/c mice for a longer follow up period of 25 weeks. This study included 30 mice that received either vehicle control (5% glucose) or 3 IV injections of SaNPs (1.6 mg IO/mL) at an interval of one month combined with AMF application (33 kA/m) after each dosing session. Fifteen mice were weighed and assigned to each group. Five mice from the treated group were subjected to IO content evaluation by the pEPR method as described above.Measurements post sacrifice included blood analyses , necropsy, gross pathology, and histopathology of vital organs. Blood analyses were conducted by the American Medical Laboratories (AML), Ltd, Herzelia, Israel. Blood was collected from the orbital sinus and spun down to separate serum, the blood and serum were stored at 4°C until analysis. Indicators of liver and kidney functions such as alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin, albumin, gamma-glutamyl transferase, alkaline phosphatase, and urea were monitored. White blood cells (WBC), red blood cells (RBC), hemoglobin, mean cell hemoglobin (MCH), mean cell volume (MCV), polymorphonuclear cells, lymphocytes, and platelets were also determined. The following tissues were collected at necropsy: heart, lung, liver, kidneys, spleen, long bone, and brain and kept in 10% NBF until sectioning.ex-vivo imaging using the CRi Maestro™ multispectral imaging system . The number of tumors/nodules in the lungs was reported, expressed either as single, or multiple nodules. A two-dimensional morphometric measurement and average area quantitation (mm2) was done on the largest nodule  present in the lung sections based on the recommendations of the Fleischner Society for measuring pulmonary nodules at CT (https://www.augmentiqs.com/) as described  started at day 10 post cell inoculation, and were applied within 2-days intervals between each cycle. The primary endpoint of the study was to record the number and size of metastases in the lungs. This was achieved by visual counting, determination of the metastases’ fluorescence intensity, and histopathology efficacy evaluation. At the end of the study, the animals were sacrificed, the lungs were excised and the number of metastases was visually counted followed by fluorescence es at CT  which reescribed .vs. untreated control.Ten BALB/c mice bearing mCherry breast cancer metastatic tumors were randomly assigned 5 to a group, weighed, and treated with 5 cycles of Sarah Nanotechnology, to mimic a chronic treatment setting, starting at day 13 post cell inoculation, each including a single IV bolus SaNP dose (1.8 mg IO/mL) to the tail vein, followed by 30 min of AMF application (33 kA/m) at 8hrs post injection. The experiment concluded when the last mouse died. The date of each animal’s death was recorded. The primary endpoint of the study was the survival of the mice; treated Histological slides were prepared by Patho-Lab Diagnostics Ltd., Ness Ziona, Israel. Tissues harvested for microscopic examination were fixed in 10% NBF for at least 24hrs. Lungs were inflated by formalin to their normal volume. Tissues were trimmed, according to the registry of industrial toxicology animal-data (RITA) standards , and dehFor the detection of IO nanoparticles, selected tissues  were stained with Prussian blue . Stainedt test and a p-value of < 0.05 was considered to be statistically significant. Comparison of results among groups was carried out by one-way analysis of variance (ANOVA). Kaplan-Meier statistical analyses were utilized to compare survival.All data are expressed as the mean ± S.D. The statistical significance of differences between groups was analyzed by Student’s TEM imaging demonstrated that SaNPs, containing several encapsulated 25 nm IO nanoparticles, exhibit a monodisperse state and amorphous or spherical shapes. The variability in shape arises from the flexible nature of the nanoparticles. Images of SaNPs with diverse shapes captured by TEM are shown in The purpose of the short-term biodistribution study was to examine the accumulation of SaNPs in the target organ, thereby establishing the optimal time for AMF application after SaNP administration. We assumed that due to the EPR effect, the SaNPs were preferentially retained in the lung metastases. The results indicated that the amount of SaNP that reaches the lungs was 2-fold higher and the highest at 8hrs post injection . The results demonstrated that SaNPs were primarily accumulated in the MPS, with the liver having the highest SaNP accumulation per organ weight. This is to be attributed to the large number of resident tissue macrophages  in the liver, followed by the spleen  and spleen (4.5 ± 1.90%), consistent with the previous findings. The average percentage of SaNPs that accumulated in the lungs of female mice was relatively low, (0.07 ± 0.07%) whereas the percentage of SaNPs found in the kidneys, heart, and brain was minor and comparable  mice were sacrificed at 3, 14, and 30 days after treatment. All animals were subjected to a full detailed necropsy and gross pathological examination following the respective scheduled termination. No mortality occurred in any of the animals throughout all observation periods. The mice well tolerated the SaNP dose with no clinical signs of toxicity after the injections. No significant changes in body weight were observed nor gross pathological findings were evident in any of the treated animals at their scheduled necropsy. Histopathological analysis of organs, indicated that no treatment-related changes were found in the organs examined . Minimal pigment laden macrophages , which were associated with minimal inflammatory (mononuclear) cell infiltration were noted in the liver and lungs of the treated animals at all timepoints. As the changes in these organs were of minimal degree, they were not considered as adverse , 23. Repvs. control group that were not considered of clinical relevance and were of no concern. Changes were detected in liver enzymes, mainly in ALT and AST at the 3 days timepoint only, which were increased in the treatment compared to the control group. The complete blood analysis biochemical profile of the animals at the day 3 timepoint is shown in p-value>0.05) whereas ALT values at the same timepoint were 3.7-fold higher in the treated group compared to the control . However, while evaluating the individual parameters, the increase was due to unusually high levels of these parameters in two of the treated animals. In the rest of the treated animals, the range of the values was comparable to those seen in the control group. In one of the treated animals, the values of AST were even lower than that seen in the control group.Blood analyses showed minor changes in the blood cell counts of the treatment No changes were detected later on, at the 14 and 30 days timepoints. The changes in ALT and AST levels at the 3 days timepoint were thought to reflect an incidental biological variation, were not related to any hepatocytic damage, and are in correlation with the pigment accumulation observed in the liver by the histopathology evaluation Figure 4The results of the chronic toxicity study highlighted that 3 repeated IV doses of the SaNP followed by AMF application did not cause any adverse effects on the general health status and body weight of all treated mice compared to the controls. All animals exhibited normal body weight gain at the end of the follow up period. The average organ weights . The two-dimensional morphometric measurement on the largest nodule  present in the lung sections revealed significant differences in the mean tumor area of the treated mice. The calculated relative average area of the measured largest metastatic nodule in this group was 3.3795 ± 1.219 mm2 in the control compared to 1.0116 ± 0.602 mm2 in the treatment mice . Of note, only in the lungs of treated animals, minimal accumulation of pigment laden macrophages was noted as demonstrated by positive Prussian blue staining which indicates IO deposition . A significant reduction in the number of metastases was identified in BALB/c mice bearing 4T1 metastatic tumors following 3 treatment cycles of Sarah Nanotechnology within 2 days intervals  of the lungs in the treated mice, indicative of viability, was significantly lower than that of the control mice. The distribution of the fluorescence in the lungs is shown in p-value 0.0241).Of note, a previous initial study aimed to establish the primary mode of action of the Sarah Nanotechnology system, examined the effects of SaNP alone (1.8 mg IO/mL), AMF alone , and SaNP + AMF application at 8hrs post injection on the number of lung metastases, following 3 treatment cycles within 2 days intervals. Five mice were assigned to each group. The results presented in A two-way ANOVA was conducted showing no statistically significant differences between the groups, probably due to the small number of animals (n=5/group). However, despite the lack of statistical significance, these results suggest that only the combination of SaNP injection and AMF application (full treatment) leads to a therapeutic effect involving a reduction in the number of metastatic nodules in the lungs of BALB/c mice.To investigate the effects of Sarah Nanotechnology treatment on animal survival in the 4T1 lung metastasis model, the mice were treated 13 days after cancer cell inoculation. Control animals were injected with 5% glucose (vehicle). The results established that following 5 treatment cycles of Sarah Nanotechnology treatment, the survival of treatment mice was significantly improved compared to that of the control.p-value 0.029) .The median survival time of the control mice was 21.6 ± 4.9 days and 29 ± 3.8 days for the treatment group  were shown to have a widespread distribution and found in various organs including the liver, spleen, kidney, heart, lungs, testis, brain, and thymus, whereas larger NPs (~250 nm) were mostly restricted to the liver and spleen, similar to SaNPs (135 nm)  .Our data showed that systemic administration of single as well as 3 repeated doses of SaNPs followed by AMF application to BALB/c mice was not associated with any significant adverse reactions nor any noticeable side effects or target organ toxicity. In particular, no necrosis was associated with the presence of SaNPs, and the observations in the liver and lungs were always sporadic and of minimal degree. The absence of inflammation and adverse reactions suggest that the SaNPs do not cause any toxicity or thermal damage, even after 3 repeated doses of SaNPs. Of note, there was a time- related recovery in the lungs and no progressive changes were observed in the liver after 25 weeks post treatment. These findings demonstrate that SaNPs at a maximal feasible dose in mice followed by AMF application, have no significant clinical or humoral acute or chronic toxicologic effects after systemic exposure.The biodistribution studies showed that the optimal time for AMF application after IV injection of SaNP was 8hrs, at this timepoint SaNP accumulation in the lung metastases, was the highest and correlated with a low blood concentration. Animal studies with other nanoparticles have shown that immediately following IV injection, nanoparticles interact with blood components such as proteins, membranes, cells, and DNA, leading to the formation of a protein ‘corona’ on the nanoparticles thereby directing them to their ultimate sites of deposition, largely through the fixed macrophages in the liver and B cells in the spleen that are part of the MPS . In lineNotably, a comprehensive analysis of nanoparticle delivery to tumor cells has shown that a median of 0.7% of the injected dose (ID) can reach the tumor . This vaAs underlined by our data, in the long-term biodistribution evaluation, the majority of SaNPs were accumulated in the liver, probably due to uptake by the resident macrophages  . MoreoveOur proof-of-concept breast cancer metastatic animal model studies demonstrated that Sarah Nanotechnology treatment was able to significantly inhibit tumor progression and prolong the survival of BALB/c bearing 4T1 metastatic tumors, that were treated with repeated cycles of Sarah Nanotechnology treatment. The results of several efficacy studies, showed a significant reduction in the number of metastases as well as in their size and viability, in the treated compared to the control mice following 3 treatment cycles of Sarah Nanotechnology.4 4T1 cells, mice started to die at day 17, and the median survival time was 26.2, 26.8, 25.6, and 27.6 days for the control and the treatment groups, respectively (Furthermore, the survival of treated mice was significantly improved compared to the control. Due to its highly aggressive nature, only few studies examining survival using the 4T1 metastatic model have been published . Of noteectively . There wThe presented magnetic hyperthermia nanoplatform is a physical approach that is not limited by the development of resistance to treatments that occurs with all the present known systemic antineoplastic approaches . The lacin vivo. In addition, they provide a solid basis for the development of Sarah Nanotechnology as a novel approach and therapeutic strategy for clinical application in treating metastatic solid tumors following the failure of all standard treatments.Our results demonstrate that Sarah Nanotechnology treatment, exhibits high specificity and efficiency in damaging and destroying metastatic cancer cells. The studies presented herein prove the feasibility and effectiveness of our approach in treating this type of cancer in BALB/c mice The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The animal study was reviewed and approved by Bar Ilan University, Israel.Conceptualization, SK, RKD, and RH. Methodology, SK, RKD, PR, AA, RK, and MC-E. Formal analysis, SK, RKD, and AN. Investigation, SK, ES, and RR. Writing – original draft preparation, SK. Writing – review and editing, SK, RR, OS, and AC. Visualization, ES and RR. Supervision, OS, GG, and AC. Project administration, RH, and OS. All authors contributed to the article and approved the submitted version.This work was funded by New Phase Ltd.Authors SK, RKD, RH, ES, ME, PR, RR, RK, AA, OS, and MC-E were employed by New Phase Ltd.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The authors declare that this study received funding from New Phase Ltd. The funder had the following involvement with the study: Study design, collection, analysis, interpretation of data, and the writing of this article.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Epidemiological studies suggest that high intake of soy isoflavones may protect against breast cancer, but causal relationships can only be established by experimental trials. Thus, we aimed to provide a systematic review of randomized controlled trials (RCTs) on the effect of an isoflavone intake on risk factors of breast cancer in healthy subjects. After a systematic literature search in PubMed, 18 different RCTs with pre- and/or postmenopausal women were included and investigated for details according to the PRISMA guideline. In these studies, isoflavones were provided by soy food or supplements in amounts between 36.5–235 mg/d for a period of 1–36 months. Breast density, estrogens including precursors, metabolites, estrogen response such as length of menstrual cycle, and markers of proliferation and inflammation were considered. However, in most studies, differences were not detectable between isoflavone and control/placebo treatment despite a good adherence to isoflavone treatment, irrespective of the kind of intervention, the dose of isoflavones used, and the duration of isoflavone treatment. However, the lack of significant changes in most studies does not prove the lack of effects as a sample size calculation was often missing. Taking into account the risk of bias and methodological limitations, there is little evidence that isoflavone treatment modulates risk factors of breast cancer in pre- and postmenopausal women. Future studies should calculate the sample size to detect possible effects and consider methodological details to improve the study quality. Breast cancer is the most frequent type of cancer in women globally. Each year, about 2.3 million women worldwide develop breast cancer, and about 685,000 people were estimated to die from breast cancer in 2020 . Women fBreast cancer is favored by race, ethnicity, family history of cancer, genetic variants and mutations of genes modulating DNA repair. Age at menarche, parity, as well as age at first pregnancy affect the risk by modulating the long-term sex hormone levels. Physical inactivity is a modifiable risk factor as well as diet. Whereas certain foods and food ingredients increase the risk of breast cancer , others like soy or isoflavones seems to be protective .More than 25 years ago, a population-based case-control study revealed a higher breast cancer rate in women of Chinese, Japanese, and Filipino ethnicities migrating to USA and Hawaii than in the countries of origin, which approximated in Asian-Americans born in the West to the U.S. white rate. However, the risk increased among Asian immigrants in the U.S. over several generations, suggesting that the Western lifestyle substantially increased the breast cancer risk .In contrast to the Western diet, the Asian diet is traditionally rich in foods produced from soybeans as main ingredients. As soy products are the major dietary source of isoflavones, the intake of isoflavones in Asia  is much higher than in Europe (0.37–4.5 mg/d) and in USA (0.73–3.3 mg/d) despite considerable variation between individual studies  to [4-(OH)-E1 + 4-(OH)-E2 + 4-(MeO)-E1] may be beneficial as 2-OH-metabolites weaken the estrogen effect [50-values for daidzein and cytochrome P450 1A1 are not available yet [In postmenopausal women, urinary excretion of E1 , E1S [501 [1S [2 ,53, prog1 [1S [2 ,53, LH [1 [1S [2 ,53, and n effect , while 4n effect . On the n effect ,51,52,53n effect  were notable yet .2 [2 [In women with different menopausal states, changes in estrogen homeostasis by isoflavone treatment are also unlikely as the serum/plasma concentration of E2 ,57, prog2 ,57,58, L2 , SHBG [52 [2 ,58, grow2 [2 , cytolog2 [2 ,57. It i2 [2 . With reTaken together, most RCTs with pre- and/or postmenopausal women did not show a response to isoflavone treatment, although the dose of isoflavones ingested and the duration of treatment varied between the studies . Breast density was determined after 10 , 12 37,,37,49,55clinicaltrials.gov. The risk of detection bias was always, and the risk of other bias often low. As the overall RoB of RCTs funded by industry was high [The overall RoB in trials with premenopausal women was often higher  than in trials with postmenopausal women  and in mixed groups . The risk of attrition bias was quite different between the studies. For most studies, the risk of selection bias, reporting bias and the risk of allocation concealment remains unclear as relevant details were not reported, and the study protocol not registered in was high ,53 or unwas high ,55, simiwas high ,48,57,58was high ,52,54,56The sample size was calculated in four trials ,55,57,58Moreover, pooling data as in meta-analyses increases the sample size and the probability to detect an effect by isoflavone treatment. A meta-analysis of eight RCTs published in 2010 investigated the impact of isoflavone-rich foods or supplements on breast density and related parameters. A small increase in breast density was detectable for premenopausal women, but not for postmenopausal women and all women.This systematic review of RCTs investigates the response of isoflavone treatment to parameters which are considered as risk factor for breast cancer. These RCTs were described in detail and assessed for RoB to provide a clear picture on the effect induced by isoflavone intake in women with different menopausal states. Moreover, each study was checked for sample size calculation to evaluate imprecision.Literature was only searched in PubMed as this has shown to be an optimal tool in the field of biomedical research, even with free access ,28. WithRisk factors of breast cancer  did not change in most trials despite a good adherence to isoflavone treatment, independent of the kind of intervention, the dose of isoflavones used and the duration of isoflavone treatment. However, the lack of significant changes does not prove the lack of effects as a sample size calculation was missing in most studies. Taking into account the RoB and methodological limitations, there is little evidence that isoflavone treatment modulates risk factors of breast cancer in pre- and postmenopausal women.Future studies should calculate the samples size based on existing results to allow clear conclusions and should report further methodological details to reduce RoB. A meta-analysis of RCTs is warranted to judge if an isoflavone intake might contribute to the prevention of breast cancer.


By incorporating the conservation of resource theory, this study examines how high-performance work practices (HPWPs) affect the employee's in-role performance (EIRP) and employee's task performance (ETP) during the coronavirus disease 2019 (COVID-19) pandemic. Furthermore, this study investigates how organization-based self-esteem (OBSE) and positive psychological capital (PPC) affect the relationship between HPWPs and outcomes of employees such as EIRP and ETP. A quantitative technique based on the survey method was used to gather the primary data of the investigation. Two hundred and eleven bank employees working in different banks of Punjab and Pakistan participated in the survey process. The PROCESS-macro was used to test the relationship among the study constructs. Our results supported all the study hypotheses, however positive psychological capital did not moderate the indirect effect of high performance work practices on employee's task performance via organization based self-esteem. This study is the earliest of its kind that focuses on HPWPs and outcomes of employees amid the COVID-19 pandemic in a developing country like Pakistan. The findings of this study provide practical implications in the post and continuing pandemic situation for organizations to human resource management to redesign workforce strategies to increase their contribution and responses to realize organizational priorities. Although researchers have explored the topic in different sectors, scant studies have investigated the potential impact, barriers, and enabling mechanisms that function as a catalyst in HPWPs during the pandemic situation. Novel coronavirus disease 2019 (COVID-19) epidemic broke out in China (Wuhan) in December 2019  by employing the conservation of resource (COR) theory in organizations to help achieve organizational objectives. COR Hobfoll,  theory sHowever, few studies have focused on how organizations could incorporate and introduce HPWPs in the banking industry , which can serve as a mediator between HPWPs and EIRP and ETP. Scholars characterized OBSE as the extent to which the workforce perceives that they are appreciated and valued by the organization  that acts as a personal resource for the individuals, enabling them in a challenging working environment . Second, we explored the mediating role of OBSE in the link between HPWPs and outcomes of employees . Third, this study examined the moderating effect of PPC on the link between HPWPs and outcomes of employees. Fourth, the moderated mediation impact of PPC and OBSE was tested in the link between HPWPs and outcomes of employees. Additionally, in this study, we overcame the gap suggested by Gahan et al. , NasurdiConservation of resource theory provides the foundation for the support of this study model that establishes that resources are the ideal set of skills helping employees to accomplish workplace tasks Hobfoll, . At presAccording to the COR theory, social, physical, supportive environmental, and cognitive resources are the significant resources that helps to protect and enhance well-being Hobfoll, , also beAdditionally, personal resources empower individuals to manage and cope with environmental stressors Hobfoll, . Based oThe burgeoning literature advocated that organizations following HPWPs indicated improved motivation, high-quality services, products, increased innovative task behaviors, creativity, job crafting, efficiency, low levels of absenteeism, and turnover of employees  having confidence (self-efficacy) to take on and put in the necessary effort to succeed at challenging tasks, (2) making a positive attribution (optimism) about succeeding at present and in the future, (3) persevering toward goals and, when necessary, redirecting paths to goals (hope) to succeed, and (4) when beset by problems and adversity, sustaining and bouncing back and even beyond (resilience) to attain success” . This study also proposes that the influence of HPWPs increases extra role performances of employees indirectly through OBSE (Hypothesis 2a and 2b). Moreover, it is anticipated that the strength of the link between HPWPs and OBSE would be contingent on the PPC level (Hypothesis 3). Additionally, based on the above discussion, we proposed a moderated mediation framework in which PPC moderates the indirect effect of HPWPs on EIRP and ETP Hypothesis 4aPPC moderates the indirect positive effect of HPWPs and EIRP via OBSE in the sense that a higher level of PPC will strengthen the indirect impact of HPWPs.Hypothesis 4bPPC moderates the indirect positive effect of HPWPs and ETP via OBSE in the sense that a higher level of PPC will strengthen the indirect impact of HPWPs.This study targeted the banking sector due to the ongoing economic crisis (amid pandemic) that has globally affected human and financial resources. It is imperative to study the factors that help understand and realign the strategies to improve the banking sector workforce performance in Pakistan. The data were collected through social contacts with bank staff and random personal visits of public and private banks. Each survey was attached with a cover letter to elucidate the aim of this study to the respondents and ensure confidentiality. The temporal separation method was adopted in this study to overcome the issues related to common method bias  to 5 (“strongly agree”). The measures used for this study are as follows: n et al.  was usede et al.  was adops et al. , which cAnderson . The Cros et al.  was usedWe used PROCESS-macro to test the relationship between the study variables. It was employed to test the complex moderated mediation as suggested by Hayes . AdditioMost of the participants were males, i.e., 148 (70.1%), whereas 64 (29.9%) were females. The age distribution indicated that 111 (52.6%) participants were between 20 and 30 years, 92 (43.6%) were between 31 and 40 years, and 8 (3.8%) were between 41 and 50 years. Educational qualification showed that 29 (13.7%) participants had MS/MPhil, 135 (64.0%) master's degree, and 47 (22.3%) had a graduate degree. The information of work experience consisted of 43 (20.4%) participants having “ <1 year,” 105 (49.8%) having “1–5 years,” 49 (23.2%) having “6–10 years,” 12 (5.7%) having “11–15 years,” and 2 (1.0%) having “21 years above.”b = 0.20, t = 3.61, and p < 0.001) and a positive impact on ETP . Further bootstrapping has also been conducted to test the indirect effects. By using PROCESS-macro, we computed a 95% CI through 5,000 samples for each mediation effect as suggested by Hayes (via OBSE was significant as 95% CI did not contain zero and b = 0.18 (95% CI ranging from 0.05 to 0.33); thus, H2a received further support. Similarly, the indirect impact of HPWPs on ETP via OBSE is insignificant as 95% CI did not contain zero and b = 0.12 (95% CI ranging from 0.01 to 0.25); thus, H2b also found further support.by Hayes . The indb = 0.12 and p < 0.001), which provides support for H3. Moreover, we also plotted the slopes for the interaction effect (HPWPs × PPC) on OBSE, as shown in Furthermore, the moderating effect of PPC has also been tested between the link of HPWPs and OBSE (mediating variable). As shown in via OBSE; it is significant for the high/low level of PPC because it does not contain zero. Moreover, via OBSE because it was not found significant for the high/low level of PPC, as zero was found between the upper and lower level CI. Moderated mediation index, as depicted in b = 0.03, boot SE = 0.01, and LL (lower limit)/UL (upper limit) = 0.05/0.01; thus, H4a was supported. This result indicated that PPC moderated the indirect effect of HPWPs on EIRP via OBSE in such a way that the higher the level of PPC will shape, the higher the level of EIRP. Additionally, b = 0.02, boot SE = 0.01, and LL/UL = 0.04/0.00); thus, H4b did not get support. This result indicated that PPC did not moderate the indirect effect of HPWPs on EIRP via OBSE.This study also examined the conditional indirect effects using the PROCESS Model-07 Hayes, . FurtherThis study investigated the impact of HPWPs concerning performance-related outcomes of employees with mediating impact of OBSE and moderating impact of PPC. Furthermore, this study also examined the moderated mediation link between the variables in the banking industry of Pakistan amid the COVID-19 pandemic.via OBSE. In other words, a higher level of PPC with OBSE provides psychological resources to employees to perform better EIRP in the presence of HPWPs, especially in stressful circumstances, e.g., COVID-19. Contrarily, PPC did not moderate the indirect effect of HPWPs on ETP via OBSE, which revealed that some factors affected the motivation of employees to perform their tasks efficiently. Subsequently, the COR theory elaborated that resource losses in the work environment have more significant influence than appreciated gains. Thus, we approbated that due to some resource loss, the ETP was not improved as it was anticipated.Generally, the results of this study provided support for most of our proposed hypotheses. The findings of our first hypothesis that proposed HPWPs positively influencing the outcomes of employees were supported and consistent with earlier studies  aid in achieving and cultivating positive employee performance.Our holistic model in the current pandemic scenario presents a unique model that further helps scholars carry out future studies. Finally, we examined the study variables and their relationships in a non-Western context in Pakistan. Also, we investigated banking sector employees in pandemic situations where resource loss is an inevitable element. To overcome this situation, the impact of necessary personal/organizational resources was explored that helps employees perform better.Our findings present numerous implications for the researchers, practitioners, and management of different organizations on how to enhance the performance of employees amid and post-pandemic situations. As scholars, Hobfoll et al.  advocateThe limitations of this study are as follows: first, this study focused on the banking industry; the findings may not be generalized in other occupational areas like manufacturing, service sectors such as textiles, telecommunication, and public sector organizations in Pakistan. Thus, future studies can be carried out in other sectors of the economy. Second, we collected data from a developing economy; future studies replicate our findings in another cultural context to examine the influence of cultural settings. Third, we used OBSE as the mediator and PPC as the moderator; future researchers are encouraged to examine some other moderators and mediators between HPWPs and outcomes of employees, for instance, personal initiative, leadership, and perceived organizational support from other theoretical viewpoints.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Faculty of Management Sciences, International Islamic University, Islamabad, Pakistan. The patients/participants provided their written informed consent to participate in this study.MZ and HK: definition of research objectives, models, and hypotheses. MC: the provision of materials  and data collection. LM: article revision and proofreading. All the authors contributed and approved the final draft for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.