Laser-Assisted High Speed Machining of 316 Stainless Steel: The Effect of Water-Soluble Sago Starch Based Cutting Fluid on Surface Roughness and Tool Wear

Laser-assisted high speed milling is a subtractive machining method that employs a laser to thermally soften a difficult-to-cut material’s surface in order to enhance machinability at a high material removal rate with improved surface finish and tool life. However, this machining with high speed leads to high friction between workpiece and tool, and can result in high temperatures, impairing the surface quality. Use of conventional cutting fluid may not effectively control the heat generation. Besides, vegetable-based cutting fluids are invariably a major source of food insecurity of edible oils which is traditionally used as a staple food in many countries. Thus, the primary objective of this study is to experimentally investigate the effects of water-soluble sago starch-based cutting fluid on surface roughness and tool’s flank wear using response surface methodology (RSM) while machining of 316 stainless steel. In order to observe the comparison, the experiments with same machining parameters are conducted with conventional cutting fluid. The prepared water-soluble sago starch based cutting fluid showed excellent cooling and lubricating performance. Therefore, in comparison to the machining using conventional cutting fluid, a decrease of 48.23% in surface roughness and 38.41% in flank wear were noted using presented approach. Furthermore, using the extreme learning machine (ELM), the obtained data is modeled to predict surface roughness and flank wear and showed good agreement between observations and predictions.     

Prevalence and impact of comorbidities on disease prognosis among patients with COVID-19 in Bangladesh: A nationwide study amid the second wave

BackgroundSocio-demographics and comorbidities are involved in determining the severity and fatality in patients with COVID-19 suggested by studies in various countries, but study in Bangladesh is insufficient.AimsWe designed the study to evaluate the association of sociodemographic and comorbidities with the prognosis of adverse health outcomes in patients with COVID-19 in Bangladesh.MethodsA multivariate retrospective cohort study was conducted on data from 966 RT-PCR positive patients from eight divisions during December 13, 2020, to February 13, 2021. Variables included sociodemographic, comorbidities, symptoms, Charlson comorbidity index (CCI) and access to health facilities. Major outcome was fatality. Secondary outcomes included hospitalization, duration of hospital stay, requirement of mechanical ventilation and severity.ResultsMale (65.8%, 636 of 966) was predominant and mean age was 39.8 ± 12.6 years. Fever (79%), dry cough (55%), and loss of test/smell (51%) were frequent and 74% patients had >3 symptoms. Fatality was recorded in 10.5% patients. Comorbidities were found in 44% patients. Hypertension (21.5%) diabetes (14.6%), and cardiovascular diseases (11.3%) were most prevalent. Age >60 years (OR: 4.83, 95% CI: 2.45–6.49), and CCI >3 (OR: 5.48, 95% CI: 3.95–7.24) were predictors of hospitalizations. CCI >4 (aOR: 3.41, 95% CI: 2.57–6.09) was predictor of severity. Age >60 years (aOR: 3.77, 95% CI: 1.07–6.34), >3 symptoms (aOR: 2.14, 95% CI: 0.97–4.91) and CCI >3 vs. CCI <3 (aOR: 5.23, 95% CI: 3.77–8.09) were independently associated with fatality.ConclusionsIncreased age, >3 symptoms, increasing comorbidities, higher CCI were associated with increased hospitalization, severity and fatality in patients with COVID-19.     

Diversity of carbapenemases in clinical isolates: The emergence of blaVIM-5 in Bangladesh

Global emergence and dissemination of carbapenemases are clinically threatening, notably in countries with endemic bla_NDM. To analyze the extent of carbapenemases in Bangladesh, 71 isolates were collected from 7 different clinical sources: wound swab (n = 38), pus (n = 13), urine (n = 9), blood (n = 4), tracheal aspirate (n = 3), pleural fluid (n = 1) and vaginal swab (n = 3) from Dhaka Medical College Hospital, Bangladesh. Among the isolates, 25 were resistant to at least one of the three carbapenems (imipenem, meropenem and doripenem), including 15 being resistant to all. These resistant isolates were identified as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, P. hibiscicola, Proteus mirabilis, Providencia stuartii and Citrobacter sedlakii. Carbapenemase detection among these 25 isolates varied in individual phenotypic assays (83% in Modified Hodge Test, 50% in Combined Disk Test for Metallo-β-lactamase prediction) as compared with the genotypes observed (96% prevalence of various carbapenemases including bla_OXA-1,48, bla_NDM-1,5, bla_VIM-2,5). bla_OXA-48 was the most prevalent gene (84%) followed by bla_NDM (72%). Coexistence of multiple gene combination such as bla_NDM+bla_OXA-48+bla_OXA-1 was prevalent (48%). Harborage of bla_VIM-5 (n = 1) was characterized for the first time, while bla_NDM-5 (n = 5) was reported contemporarily with a recent study in Bangladesh. Presence of plasmids (64%) and integron class 1 (100%) signifies the transferable potential of resistant traits. The emergence of such new variants along with the presence of the mobile genetic elements demands strict surveillance and combating strategies.     

Hepatitis C virus infection in a community in the Nile Delta: risk factors for seropositivity

The purpose of this study was to identify risk factors for hepatitis C virus (HCV) infection in a rural village in the Nile Delta with a high prevalence of antibodies to HCV (anti-HCV). One half of the village households were systematically selected, tested for anti-HCV, and interviewed: 973 of 3,999 (24.3%) subjects were anti-HCV-positive (reflecting prior HCV infection but not necessarily current liver disease), with nearly equal prevalence among males and females. Anti-HCV prevalence increased sharply with age among both males and females, from 9.3% in those 20 years of age and younger to >50% in those older than 35, suggesting a cohort effect with reduced transmission in recent years. Multivariate regression was used to estimate independent effects of risk factors on seropositivity. Among those over 20 years of age, the following risk factors were significantly associated with seropositivity: age (P <.001); male gender (odds ratio [OR] = 2.5, 95% CI = 1.3-4.7); marriage (OR = 4.1, 2.4-6.9); anti-schistosomiasis injection treatment (OR = 2.0, 1.3-2.9); blood transfusion (OR = 1.8, 1.1-2.9), invasive medical procedure (surgery, catheterization, endoscopy, and/or dialysis) (OR = 1.5, 1.1-1.9); receipt of injections from "informal" health care provider (OR = 1.3, 1.0-1.6); and cesarean section or abortion (OR = 1.4, 1.0-1.9). Exposures not significantly related to anti-HCV positivity in adults included: history of, or active infection with, Schistosoma mansoni, sutures or abscess drainage, goza smoking in a group, and shaving by community barbers. Among those 20 years old or younger, no risk factors were clearly associated with anti-HCV positivity; however, circumcision for boys by informal health care providers was marginally associated with anti-HCV (OR = 1.7, 1.0-3.0). Prevention programs focused primarily on culturally influenced risks in rural Egyptian communities are being implemented and evaluated.     

Splenomegaly, pancytopenia and pregnancy: a case report and review of the literature

We present a 35-year-old previously healthy primigravida who presented at 26^4/7 weeks of gestation with pancytopenia and hepatosplenomegaly. She received 10 transfusions and delivered at 34^4/7 weeks of gestation by cesarean section. Two months later following splenectomy, she was diagnosed with malaria. Physicians should have a high index of suspicion for malaria in the context of splenomegaly and pancytopenia in pregnancy even in the absence of fever.     

Inhibition of human blood platelet aggregation and the stimulation of nitric oxide synthesis by aspirin

Incubation of platelet-rich plasma with 80 microM aspirin that resulted in the inhibition of both the secondary phase of ADP induced platelet aggregation and prostaglandin synthesis simultaneously stimulated the production of NO in platelets. Furthermore it was found that the treatment of platelet-rich plasma either with 80 microM ibuprofen or salicylic acid, like aspirin, which inhibited the secondary phase of platelet aggregation by ADP and prostaglandin synthesis, also stimulated the production of NO in the absence of added ADP. However the inhibition of prostaglandin synthesis by ibuprofen or salicylic acid, unlike aspirin, was transient in nature. Incubation of washed platelets with any of these three compounds also stimulated NO synthesis indicating that the effect of these compounds was not mediated through plasma proteins. The in vitro effect of aspirin on the increase of NO in platelets could also be demonstrated by in vivo exposure of platelets to the compound. It was concluded that either a temporary or a lasting inhibition of prostaglandin synthesis by these inhibitors resulted in the synthesis of NO in resting platelets. Since NO is a potent inhibitor of platelet aggregation the inhibition of platelet aggregation, by these compounds may not be the consequence of the inhibition of prostaglandin synthesis alone, but could also be related, at least partly, to the stimulated synthesis of NO by these inhibitors.     

Coronary stenting with a new ultra-short balloon expandable device: Early and late animal results

The early and late effects of a new balloon-expandable coronary stent (Boneau II) were studied in 16 adult mongrel dogs. Thirty-three balloon-expandable stents were deployed using standard transfemoral coronary angioplasty technique. Single stents were placed in eight dogs and multiple (two to four) stents were placed in eight dogs. Intravenous heparin (3,000 units) was administered at the beginning of the procedure. Aspirin, dipyridamole, dextran, and warfarin were not administered before or after the procedure. All stent deployments were successful. Angiographic or pathologic examinations were performed within 24 hr of deployment on two of the dogs, at 2 weeks on two of the dogs, at 2 months on three of the dogs, at 6 months on six of the dogs, and at 1 year on three of the dogs. All successfully deployed stents were noted to be widely patent. There was no evidence of side-branch vessel occlusion. There was no evidence of acute or late vessel thrombosis. Histologic examination at 2 months showed a mean intimal thickness of 153 μm. The stainless steel Boneau II coronary stent is relatively short and easily deployed. This balloon-expandable coronary stent was successfully deployed in normal canine arteries without the use of anticoagulation or antiplatelet therapy before or after the procedure. The Boneau II intracoronary stent has a very low thrombogenic potential in dogs.     

Different catecholamines induce different patterns of takotsubo-like cardiac dysfunction in an apparently afterload dependent manner

Background

Takotsubo cardiomyopathy (TCM) is characterized by regional left ventricular dysfunction that cannot be explained by an occlusive lesion in a coronary artery. Catecholamines are implicated in the pathogenesis of TCM but the mechanisms involved are unknown. Because the endogenous and the most commonly used exogenous catecholamines have well defined adrenoceptor subtype affinities, inferences can be made about the importance of each adrenoceptor subtype based on the ability of different catecholamines to induce TCM. We therefore studied which of five well-known catecholamines, that differ in receptor subtype affinity, are able to induce TCM-like cardiac dysfunction in the rat.

Methods

255 rats received intraperitoneally isoprenaline (β₁/β₂-adrenoceptor agonist), epinephrine (β₁/β₂/α-adrenoceptor agonist), norepinephrine (β₁/α-adrenoceptor agonist), dopamine (α/β₁/β₂-adrenoceptor agonist) or phenylephrine (α-adrenoceptor agonist). Each catecholamine was given in five different doses. We measured blood pressure through a catheter inserted in the right carotid artery and studied cardiac morphology and function by echocardiography.

Results

All catecholamines induced takotsubo-like cardiac dysfunction. Isoprenaline induced low blood pressure and predominantly apical dysfunction whereas the other catecholamines induced high blood pressure and basal dysfunction. In another set of experiments, we continuously infused hydralazine or nitroprusside to rats that received epinephrine or norepinephrine to maintain systolic blood pressure < 120 mm Hg. These rats developed akinesia of the apex instead of the base. Infusion of phenylephrine to maintain blood pressure > 120 mm Hg after isoprenaline administration prevented apical TCM-like dysfunction.

Conclusions

Catecholamine-induced takotsubo-like cardiac dysfunction appears to be afterload dependent rather than depend on stimulation of a specific adrenergic receptor subtype.     

Insulin‐like growth factor‐II: its role in metabolic and endocrine disease

Insulin‐like growth factor‐II (IGF‐II) is a widely expressed 7·5 kDa mitogenic peptide hormone. Although it is abundant in serum, understanding of its physiological role is limited compared with that of IGF‐I. IGF‐II regulates foetal development and differentiation, but its role in adults is less well understood. Evidence suggests roles in a number of tissues including skeletal muscle, adipose tissue, bone and ovary. Altered IGF‐II expression has been observed in metabolic conditions, notably obesity, diabetes and the polycystic ovary syndrome. This article summarizes what is known about the actions of IGF‐II and its dysregulation in metabolic and endocrine diseases. The possible causes and consequences of dysregulation are discussed along with the implications for diagnostic tests and future research.     

Low-dose recombinant properdin provides substantial protection against Streptococcus pneumoniae and Neisseria meningitidis infection

Modern medicine has established three central antimicrobial therapeutic concepts: vaccination, antibiotics, and, recently, the use of active immunotherapy to enhance the immune response toward specific pathogens. The efficacy of vaccination and antibiotics is limited by the emergence of new pathogen strains and the increased incidence of antibiotic resistance. To date, immunotherapy development has focused mainly on cytokines. Here we report the successful therapeutic application of a complement component, a recombinant form of properdin (P_n), with significantly higher activity than native properdin, which promotes complement activation via the alternative pathway, affording protection against N. menigitidis and S. pneumoniae. In a mouse model of infection, we challenged C57BL/6 WT mice with N. menigitidis B-MC58 6 h after i.p. administration of P_n (100 µg/mouse) or buffer alone. Twelve hours later, all control mice showed clear symptoms of infectious disease while the P_n treated group looked healthy. After 16 hours, all control mice developed sepsis and had to be culled, while only 10% of P_n treated mice presented with sepsis and recoverable levels of live Meningococci. In a parallel experiment, mice were challenged intranasally with a lethal dose of S. pneumoniae D39. Mice that received a single i.p. dose of P_n at the time of infection showed no signs of bacteremia at 12 h postinfection and had prolonged survival times compared with the saline-treated control group (P < 0.0001). Our findings show a significant therapeutic benefit of P_n administration and suggest that its antimicrobial activity could open new avenues for fighting infections caused by multidrug-resistant neisserial or streptococcal strains.Pneumococcal and meningococcal infectious diseases remain a serious threat to public health. Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and a major cause of otitis media, septicemia, and meningitis (1, 2). S. pneumoniae is responsible for ∼1.2 million deaths per year worldwide, with young children and immunocompromised patients at particular risk (3). Neisseria meningitidis causes epidemic bacterial meningitis and septicemia, with high mortality in children and young adults (4). The impact of meningococcal disease on human health is defined by both the risk and the severity of invasive meningococcal infections, with unacceptably high mortality rates, ranging from 10% in patients under optimal clinical therapy with the latest generation of antibiotics to up to 40% in patients with untreated septicemia. Almost one-third of those who survive invasive infections are left with long-term disabilities and long-term morbidity. Globally, the World Health Organization estimates that ∼1.2 million cases of invasive meningococcal infections occur annually, leading to more than 135,000 fatalities (5).Vaccination programs have reduced the rates of infection in developed countries, but neonates and elderly adults remain especially vulnerable (6, 7). The efficacy of vaccination is further limited by the emergence of new strains of S. pneumoniae and N. meningitidis.The complement system plays a major role in the host resistance to both pathogens (8–13). Complement is activated via three routes: the classical pathway, the lectin pathway, and the alternative pathway. Activation of the classical and lectin pathways is mediated by specific recognition molecules. Binding of C1q to the bacterial surface or the Fc region of antibody initiates the classical pathway. The lectin pathway is initiated by carbohydrate recognition molecules, including mannan-binding lectin, ficolins, and collectin 11, which bind directly to bacterial polysaccharides. Activation of the classical or lectin pathway leads to the formation of a C3 convertase (C4b2a), which splits C3 into the biologically active fragments, C3b and C3a. C3b can bind covalently to an activating surface, and hundreds of molecules of C3b can be deposited in close proximity to the C3 convertase complex. Accumulation of C3b close to C4b2a forms the classical pathway C5 convertase C4b2a(3b)_n, in which C4b and C3b form a binding site for C5, orienting it for cleavage by C2a (14, 15).The mechanisms initiating the alternative pathway are less well understood. It is widely accepted that the alternative pathway maintains a continuous state of low-rate activation, which is held in check by potent negative regulators of activation on nonactivating surfaces, such as the surface of host cells. Turnover of the alternative pathway is initiated either by the provision of C3b via the classical pathway, the lectin pathway, or complement-independent proteolysis of C3 or by the spontaneous hydrolysis of C3 to form C3(H₂O). C3b or C3(H₂O) bind factor B to form either the C3bB or C3(H₂O)B zymogen complex. In this complex, factor B is cleaved by factor D, releasing a Ba fragment. The activated C3bBb or C3(H₂O)Bb fragments are themselves C3 convertases, which in turn cleave more C3 into C3a and C3b. Unchecked, the accumulation of C3b rapidly leads to the formation of more alternative pathway convertase complexes, resulting in a physiologically critical positive feedback mechanism—the amplification loop of complement activation (16). The alternative pathway thus amplifies complement activation initiated by any of the three pathways, making it an attractive target for therapeutic intervention designed to modulate complement-mediated immunity and/or inflammatory processes (17).Deposition of C3b and iC3b on the bacterial surface is a key step in the immune response against S. pneumoniae, because complement-mediated opsonisation is essential for clearance of S. pneumoniae through phagocytosis (8). Lysis of bacteria, owing to formation of the membrane attack complex complex, is the critically important biological activity of complement in the defense against N. meningitidis (10). Inherited or acquired deficiencies of the alternative pathway are associated with a high risk of recurrent bacterial infection. Factor B deficiencies significantly increase the risk of S. pneumoniae and Pseudomonas aeruginosa infection (9, 18). In a mouse model of properdin deficiency, the severity of polymicrobial peritonitis was significantly greater in deficient mice compared with their WT littermates (19). Properdin deficiency in humans has been associated with a high risk of meningococcal infections, especially with unusual infective serotypes, such as W-135 and Y (10, 20, 21). In addition, opsonophagocytosis of S. pneumoniae was found to be severely compromised in properdin-deficient sera, and reconstitution of properdin-deficient sera with purified properdin restored the opsonic activity and killing of S. pneumoniae by polymorphonuclear leukocytes (22, 23).Properdin is the only known positive physiological regulator of complement activation. It stabilizes and extends the half-life of the surface-bound C3 convertase C3bBb, and inhibits its degradation by factor I (24–26). In their pioneering 1954 work, Pillemer et al. (26) first described properdin as a serum protein that mediates complement activation and antimicrobial activity in absence of antibodies.Properdin is present in serum at a concentration of ∼5–15 μg/mL (27). Unlike most other complement components, properdin is not synthesized in the liver but rather is expressed by other cells, including monocytes, T cells, mast cells, and granulocytes (19, 28–30). Properdin monomers can assemble into dimers (P₂), trimers (P₃), and tetramers (P₄), formed by head-to-tail association of monomers (each ∼53 kDa) (31, 32). Properdin aggregates, so-called “activated” properdin (P_n), are considered artificial higher-order oligomers formed during the purification of properdin from plasma or during subsequent freeze–thaw cycles (33). The functional activity of properdin increases with the size of the polymers formed (34). By increasing the half-life of the alternative pathway C3 convertase, properdin antagonizes the functional activity of complement factor H, an abundantly expressed plasma component, which promotes inactivation of the alternative pathway C3 convertase and of all C5 convertases of complement by accelerating the decay of these enzyme complexes through binding to complex-bound C3b and by serving as a cofactor in the factor I-mediated conversion of C3b to its inactive form, termed iC3b (35). Interestingly, the two pathogens used in this study were previously shown to express distinct microbial surface components that sequester factor H from host plasma, leading to resistance to the complement-mediated immune clearance of these pathogens (36, 37).In the present study, we addressed the role of the alternative pathway and the effect of administration of recombinant properdin as a tool for boosting alternative pathway activity to augment the immune response against S. pneumoniae or N. meningitidis.