Four Waves of the COVID-19 Pandemic: Comparison of Clinical and Pregnancy Outcomes

During the last two and a half years, clinical manifestations, disease severity, and pregnancy outcomes have differed among pregnant patients with SARS-CoV-2 infection. These changes were preceded by the presence of new variants of SARS-CoV-2, known in the literature as variants of concern. The aim of this study is to describe the differences between maternal clinical characteristics and perinatal outcomes among pregnant women with COVID-19 during four waves of the COVID-19 epidemic in Serbia. This retrospective study included a series of 192 pregnant patients who were hospitalized due to the severity of their clinical status of SARS-CoV-2 infection. During four outbreaks of COVID-19 infection in Serbia, we compared and analyzed three sets of variables, including signs, symptoms, and characteristics of COVID-19 infection, clinical endpoints, and maternal and newborn parameters. During the dominance of the Delta variant, the duration of hospitalization was the longest (10.67 ± 1.42 days), the frequency of stillbirths was the highest (17.4%), as well as the frequency of progression of COVID infection (28.9%) and the requirement for non-invasive oxygen support (37%). The dominance of the Delta variant was associated with the highest number of prescribed antibiotics (2.35 ± 0.28), the most common presence of nosocomial infections (21.7%), and the highest frequency of corticosteroid therapy use (34.8%). The observed differences during the dominance of four variants of concern are potential pathways for risk stratification and the establishment of timely and proper treatments for pregnant patients. Early identification of the Delta variant, and possibly some new variants with similar features in the future, should be a priority and, perhaps, even an opportunity to introduce more accurate and predictive clinical algorithms for pregnant patients.     

The Emergence of SARS-CoV-2 within the Dog Population in Croatia: Host Factors and Clinical Outcome

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog populations. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralising antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Due to the retrospective nature of this study, samples for viral isolation and PCR were unavailable. Still, seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.     

Dental caries in postwar Bosnia and Herzegovina

OBJECTIVES: To present the prevalence of dental caries in postwar Bosnia and Herzegovina (BH). METHODS: A survey focused on dmft and DMFT indices was carried out in four cantons of the Federation of BH in 1997. The dental health of 6- and 12-year-olds was assessed in random samples (n = 238 and 318, respectively). DMFT index in adult population was assessed in clients coming to dental offices in the same area (35-44-year-olds; n = 401). All the subjects were clinically investigated. RESULTS: During the 1991-95 war, all four cantons were affected by the migration of population. The population per dentist ratio considerably increased in three cantons. In 6-year-olds, the average dmft (+/-SD) was 4.9 +/- 4.0, and 86% of the children were affected with dental caries. The average DMFT of 12-year-olds was 6.2 +/- 3.9. On the average, 94% of the 12-year-olds were affected with dental caries. Mean DMFT of adult clients was 15.1 +/- 7.0. Almost every adult (98%) was affected with dental caries. CONCLUSIONS: The dental status in postwar BH is rather poor and the mean DMFT in all investigated age groups may be considered high. The detrimental effect of 1991-95 war on social conditions and the health care system should be considered in explaining such poor dental health. Despite the limitations, the presented data may be used to assess the treatment needs, assure the visibility for dental issues in BH, and help the west European countries to plan dental services for refugees from BH.     

Prevention and Treatment Of Heterotopic Ossification After Spinal Cord Injury

Abstract

Background/Objectives: Heterotopic ossification (HO) is a frequent, irreversible complication afterspinal cord injury (SCI). The objective of this article is to explain the etiology of HO; present new advances in prevention, diagnosis, and management of this complication; and provide a suggested algorithm for clinical management.

Etiology: Although still hypothetical, trauma and overexpression of bone morphogenic protein(s) in traumatized soft tissue appear to play important roles as initiating factors of HO.

Prevention: Preventive use of nonsteroidal antiinflammatory agents (NSAIDs) reduces the incidence of HO by a magnitude of 2 to 3.

Management: Early determination of serum creatine phosphokinase may have a diagnostic value in predicting the onset and severity of HO, and an NSAID may be added to etidronate therapy in the initial inflammatory phase of HO formation until C-reactive protein Ieveis return to normal range. Surgery is indicated in a subset of patients, and a regimenthat includes radiation therapy may prevent postoperative recurrence.

Conclusion: Significant progress has been made in the early prevention and management of HO. Further studies are needed to elucidate the etiology.     

C-reactive protein and erythrocyte sedimentation rate in patients with heterotopic ossification after spinal cord injury

BACKGROUND/OBJECTIVE: Formation of heterotopic ossification (HO) in soft tissue after spinal cord injury (SCI) is associated with various degrees of inflammation. Recent studies have shown that inhibition of inflammatory reaction with nonsteroidal anti-inflammatory drugs is an effective prevention of HO after SCI. The goal of this study was to monitor the activity of the most widely used indicators of acute inflammation--namely, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)--in patients with HO. METHODS: In a retrospective study, the results of 37 patients with HO were evaluated. There were 25 patients with tetraplegia and 12 with paraplegia. The age (mean +/- SD) of the patients was 28 +/- 8 years (range = 19-46 years). The patients were admitted to the rehabilitation center 2 to 5 weeks after SCI. HO was confirmed by bone scintigraphy. Blood samples were obtained from the patients at the time of diagnosis of HO and during the therapy. ESR was measured with the Westergren method, and serum CRP was determined by enzyme-linked immunosorbent assay. RESULTS: In the acute stage of HO, both tests were elevated in all patients. In the later stages when clinical signs and symptoms of inflammation were resolving, both tests showed a gradual decline. When clinical signs and symptoms of inflammation (fever, acute soft tissue swelling, and erythema) were not present, the concentration of CRP was normal in 91.2% of patients, whereas only 17.6% of patients had normal ESR. Mean serum concentrations of CRP were 8.9 +/- 5.6 mg/L in the inflammatory phase and 0.9 +/- 0.6 mg/L in the noninflammatory phase. CONCLUSION: The data indicate that serum CRP is a useful and more specific test than is ESR for monitoring the inflammatory activity of HO after SCI. The normalization of CRP was seen during the first 3 to 4 weeks of etidronate therapy, indicating a resolution of acute-phase inflammatory reaction.     

ONCOPROTEINS AND TUMOR SUPPRESSOR PROTEINS IN CONGENITAL SACROCOCCYGEAL TERATOMAS

Congenital sacrococcygeal teratoma SCT is the most common germ cell tumor of infancy and childhood with a female preponderance. Most SCTs are diagnosed at birth, are benign, and consist of fully differentiated, mature tissues. Tumorigenesis of SCTs remains poorly understood. Almost nothing is known about possible oncogene activation or tumor suppressor inactivation in these rare tumors. We describe the presence of various oncoproteins and tumor suppressor proteins in eight cases of congenital SCT. The following oncogenes were examined: ras family c-H-, c-N-, and c-K-ras , early genes fos, jun , and tumor suppressor genes p53 and nm23-H-1 . There was no relationship between the intensity of expression of these oncoproteins and tumor suppressor genes and the following parameters: tumor size, age, and survival of the patients. We did not observe any difference, however, between the expression of the examined oncogenes and tumor suppressor genes nm23 and p53 in immature and mature teratomas. Our findings suggest that the ras family of oncogenes, fos and jun oncogenes, and nm23 and p53 tumor suppressor genes are present in congenital SCT, indicating a possible role in genesis and development of these tumors.     

Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons

The regulation of metal ion transport within neurons is critical for normal brain function. Of particular importance is the regulation of redox metals such as iron (Fe), where excess levels can contribute to oxidative stress and protein aggregation, leading to neuronal death. The divalent metal transporter 1 (DMT1) plays a central role in the regulation of Fe as well as other metals; hence, failure of DMT1 regulation is linked to human brain pathology. However, it remains unclear how DMT1 is regulated in the brain. Here, we show that DMT1 is regulated by Ndfip1 (Nedd4 family-interacting protein 1), an adaptor protein that recruits E3 ligases to ubiquitinate target proteins. Using human neurons we show the Ndfip1 is upregulated and binds to DMT1 in response to Fe and cobalt (Co) exposure. This interaction results in the ubiquitination and degradation of DMT1, resulting in reduced metal entry. Induction of Ndfip1 expression protects neurons from metal toxicity, and removal of Ndfip1 by shRNAi results in hypersensitivity to metals. We identify Nedd4–2 as an E3 ligase recruited by Ndfip1 for the ubiquitination of DMT1 within human neurons. Comparison of brains from Ndfip1^−/− with Ndfip1^+/+ mice exposed to Fe reveals that Ndfip1^−/− brains accumulate Fe within neurons. Together, this evidence suggests a critical role for Ndfip1 in regulating metal transport in human neurons.     

Effect of impulsin treatment of interferon production and antiviral resistance of mice.

The effect of N-(2-hydroxyethyl)-palmitamide (Impulsin, Spofa)--an active endogenous compound which is recommended for preventing virus infection of the respiratory tract--on interferon production in mice stimulated with double stranded RNA and on the course of disease caused by encephalomyocarditis virus (EMC) was studied. Impulsin itself did not stimulate interferon production in mice treated per os or intravenously. But repeated application of this drug per os induced a macrophage activation, reflected by enhanced interferon production in vitro. When the interferon stimulation was delayed until 4 to 10 days after the first dose of Impulsin, interferon response to ds-RNA was slightly increased. After this phase of enhanced activity a decreased production of interferon was observed. Impulsin was not significantly effective in protecting mice from lethal dose of EMC virus. Application of this drug had an inhibitory effect on the toxicity of ds-RNA. A possible explanation of the mechanism by which Impulsin decreased the toxicity of virus in the organism is discussed.