Dr. Darko Nozic
Clinics of Infectious and Tropical Diseases, Military Medical Academy, Belgrade, Serbia.

ISBN 978-93-91215-55-2 (Print)
ISBN 978-93-91215-63-7 (eBook)
DOI: 10.9734/bpi/hmmr/v14

This book covers key areas of medicine and medical research. The contributions by the authors include N-myc downstream-regulated gene-1, pancreatic cancer, hypoxia, cellular differentiation, epigenetic regulation, maternal age, parity, gestational age, high risk behavior, white spot lesions, demineralization, treatment, fluoride, micro abrasion, computed tomography, echocardiography, imaging, palliative care, acute kidney injury, aetiology, resource constraint regions, global developmental delay, Karyotype, marker chromosome, epitheloid haemangioma, tumor, vascular, histopathological diagnosis, expression system, human coagulation factor VII, gene expression, herniation, endotracheal tube cuff, swelling, nasopharangeal, para-tracheal region, cervical Tunisian cancer, tympanoplasty, ossiculoplasty, otologic surgical procedures, autograft, titanium, cartilage, pediatrics, sports nutrition, catabolism. This book contains various materials suitable for students, researchers and academicians in the field of medicine and medical research.


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Objectives: The hypoxia-inducible and differentiation-related protein N-myc downstream-regulated gene-1 (NDRG1) is a potential biomarker in pancreatic cancer. The effects of the differentiating histone deacetylase inhibitor trichostatin A (TSA) in human pancreatic cancer cell lines representing different tumour stages were investigated because NDRG1 expression is diminished in high-grade tumours. Cancer is a genetic disease characterized by inherited or sporadic mutations in tissue homeostasis, cell cycle control, and apoptosis genes.

Methods:  TSA was used to treat PANC-1 (poorly differentiated) and Capan-1 (moderately to well-differentiated) cells. Microscopic analyses, colorimetric assays, cell counts, real-time polymerase chain reaction, and Western blotting were used to evaluate the effects in vitro.

Results: PANC-1 cells were treated with 0.5 M TSA for four days. Cellular differentiation was restored, proliferation was suppressed, and p21Cip1 protein expression was increased. Trichostatin A upregulated NDRG1 mRNA and protein levels under normoxia from day 1 and by 6-fold by day 4 (P < 0.01 at all time points). After 24 hours under hypoxia, NDRG1 expression was further in-creased in differentiated cells (P < 0.01). Other hypoxia-regulated genes showed positive changes in their expression.

Conclusions: Histone deacetylase inhibitors have the potential to be a novel epidrug for pancreatic cancer, as they reverse the undifferentiated phenotype, helping patients to overcome resistance and respond better to traditional cytotoxic treatments.

Introduction and Objectives: Birth weight is an important determinant of child survival and development. Low birth weight is an index of our status of public health, maternal health and nutrition. The major challenge in the field of public health is to identify the factors influencing low birth weight and to institute remedial measures. The study was attempted to assess prevalence of low birth weight and its risk factors affecting low birth weight was conducted among 300 mothers and their respective live born baby in GMCH, Guwahati metro, Assam.

Materials and Methods: A cross sectional study design was carried out in a government hospital among 300 mothers using interviewer administered questionnaire. All 300 postnatal mothers who delivered in the hospital during study period were included in the study except still births. All babies were weighted on standard beam balance within 24 hours of delivery and mother’s height was measured by height measuring stand. Bivariate and multivariate logistic regression was employed to identify the predictors at p<0.001 and p<0.05.

Results and Analysis: The prevalence of low birth weight was found as 26.0% (95%, CL=21.36-31.24) in 300 samples. 50% of LBW was found in the age group of mothers <18 yrs. Low birth weight was significantly risk with maternal age <18 years (OR=3.06* 95%Cl=1.24-3.52), height of the mother <145 cm (OR=2.72* 95%CL=1.61-4.62), history of ANC visit <3(OR=1.90* 95% Cl=1.03-3.52), multiple pregnancy (OR=5.95* 95% Cl=1.07-33.13), gestational age <37weeks (OR=10.00*15 95% Cl=4.53-22.09). Female child (OR=1.02, 95% Cl=0.61-1.72) and preterm birth (OR=10.00, 95%Cl=4.53-22.09), weight gain during pregnancy <6 kg (OR=1.98 95%Cl=0.88-4.44), history of high risk behavior(use of tobacco) (OR=8.84 95%Cl=0.91-86.28), iron and folic acid consumption (OR=1.44, 95%CI: 0.35-5.90), status of previous birth (OR=2.73, 95%CI: 0.81-9.14), were found to be higher risk of LBW.

Discussion and Conclusion: The prevalence of low birth weight was found to be very high and it was associated with many risk factors related to maternal health and services. Hence it is recommended to improve maternal health through strengthening the existing maternal services at the basic level of community.

White Spot Lesions in Patients with Orthodontic Appliances

Irena Gavrilovikj

Highlights on Medicine and Medical Research Vol. 14, 5 June 2021, Page 23-39

White spot lesions (WSLs) can appear during and after fixed orthodontic treatment as undesirable situation on the teeth and can compromise results of the treatment and facial esthetic. White spots lesions are defined as areas of demineralization on tooth enamel surface that can occur during the treatment with fixed orthodontic appliances, around brackets, tubes or orthodontic rings. They are located on the labial surface of the teeth mostly on the labial - gingival part on the crown of the teeth. The white spots can be seen even after 1 month of bonding fixed appliances or after 6 or 12 months. The reason for the appearances of WSLs is the process of demineralization of the enamel of the tooth. Orthodontist can and should minimized those undesired complication during the orthodontic treatment.

There are several risk factors for appearing of WSLs. The most common reason for this phenomenon is inappropriate and poor oral hygiene. For avoiding side effects of having orthodontic braces, maintaining excellent oral hygiene is require, before bonding fixed orthodontic appliances. In literature there are numerous studies for the prevention and treatment of white spot lesions. The use of fluoride (in toothpaste, gels and solutions for the mouth, in bonding materials for orthodontic braces, fluoride varnish), Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) in topical crème, micro abrasion and using resin to full fil lesions, can greatly contribute to the process of remineralization of enamel and gave successful results of treatment of WSLs.

ST-elevation Due to Primitive Extracardiac Origin. Differential Diagnosis and Review of Literature

Amabile Valotta, Lorenzo Grazioli Gauthier, Marco Moccetti

Highlights on Medicine and Medical Research Vol. 14, 5 June 2021, Page 40-46

Introduction: Vast of cases ST elevation is due to coronary occlusion. Metastatic disease has been identified as a rare case of Acute Myocardial Infarction or artery occlusion.

Case Description: This case is about a 65yo man with a diagnose of stage IV Thymic Carcinoma in 2012, with two recurrences and past surgical treatment followed by radiation and chemotherapy. From that time, CPAP addicted for respiratory failure. He went to emergency department with worsening dyspnoea in the last few days. The ECG showed an ST-elevation in DI-aVL and V4-V6 suggesting an Acute Coronary Syndrome (ACS). The emergency coronary angiogram showed no significant coronary artery stenosis. The transthoracic echo revealed a mass infiltrating the left ventricular myocardium with consequent akinesia of lateral and anterior wall. A thoracic CT scan revealed a mass of 17*10*12 cm that infiltrated the myocardium surrounding the left circumflex coronary artery, which was the reason of ST-elevation.

Discussion: After multidisciplinary medical evaluation, considering the clinical context and the surgical risk, we dropped to perform any other invasive or bioptic exam. In agreement with the patient and his relatives, the patient was hospitalized Palliative Care Unit.

Conclusion: The ECG changes due to metastatic lesions or myocardial infiltration are different from those of an ACS. They are characterized by the persistence of ST-elevation without the typical evolution such as Q waves or T inversion.  In addition, in any patient with history of malignancies, multidisciplinary discussion and multimodality imaging play a key role for the correct diagnosis and management.

Acute Kidney Injury in Children: A 3-Year Retrospective Analysis at Komfo Anokye Teaching Hospital, Ghana

Sampson Antwi, Anima Sarfo, Abigail Amoah, Anna Serwaa Appia, Esther Obeng

Highlights on Medicine and Medical Research Vol. 14, 5 June 2021, Page 47-55

Background/Aims: Acute kidney injury (AKI) is a relatively common condition encountered in everyday paediatric practice. It remains a significant contributor to preventable deaths especially in resource constraint regions of the world largely due to lack of dialysis services. AKI remains a significant contributor to the mortality of critically ill children. Mortality outcomes depend on such factors as aetiology, medical setting, co-morbidities, and availability of dialysis therapy.

This 3-year data analysis (2010-2012) was undertaken to determine the aetiology and treatment/mortality outcomes of children with AKI presenting to a Teaching Hospital in Ghana. AKI was defined in this analysis by the RIFLE and KDIGO criteria.

Results: Two hundred and six (206) cases of AKI were recorded over the period out of a total of 664 renal cases.

Haemoglobinuria, obstructive uropathy and tumour infiltration of the kidneys were the leading causes of AKI (37.8%). 9.2% of cases were diarrhoeal-related with glomerulonephritides occurring in 12.1% of cases.

Seventy-one (34.5%) of the 206 AKI cases required dialysis which could only be provided for 25 (35.2%), 16 (64%) of whom survived.

Forty-three (20.9%) children died, while 144 (69.9%) survived.

Thirty-one (72%) of the patients who died needed dialysis.

Conclusion: In comparison to previous studies across the world, there is huge burden of AKI among hospitalized children in Kumasi, Ghana.

Haemoglobinuria and tumour-related conditions accounted for most cases of AKI more than diarrhoea-associated conditions and postinfectious glomerulonephritis as were previously reported or postulated.

Most AKI deaths were related to lack of dialysis service. In view of the less technical requirements compared with other modalities of renal replacement therapy, peritoneal dialysis should be promoted across Africa to curtail needless deaths from AKI.

Impact of Microarray on Supernumerary Marker Chromosome and Global Developmental Delay

Sumitra Bachani, Vatsla Dadhwal, Deepika Deka

Highlights on Medicine and Medical Research Vol. 14, 5 June 2021, Page 56-62

Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that are equal in size or smaller than chromosome 20 and it can be recognised or characterised by conventional karyotype analysis. The molecular characterisation of sSMCs derived from chromosome 15 in prenatal diagnosis in a 38-year-old female is presented in this paper. A combination of a detailed ultrasound examination and karyotype analysis, can provide more precise and rapid prenatal diagnosis of sSMCs.

A Case Report on Epithelioid Haemangioma of the Forehead

Surya Rao Rao Venkata Mahipathy

Highlights on Medicine and Medical Research Vol. 14, 5 June 2021, Page 63-67

A tumor of soft tissues developing from the vascular endothelium is known as epitheloid haemangioma. Epitheloid haemangioma are rare tumours of the vascular endothelium. Here, we present a 22 year old patient with a swelling of the forehead region mimicking clinically as a sebaceous cyst. It was a histopathological diagnosis of an epitheloid heamangioma. She was observed for two years and there was no recurrence throughout that time. The cutaneous manifestation of this condition is extremely rare, hence this case is being recorded.

Developing the Expression of Recombinant Human Coagulation Factor VII by the Lizard Leishmania Expression System

Sina Mirzaahmadi, Golnaz Asaadi-Tehrani, Mojgan Bandehpour, Nooshin Davoudi, Leila Tahmasbi, Nahid Hosseinzadeh, Hasan Mirzahoseini, Kazem Parivar, Bahram Kazemi

Highlights on Medicine and Medical Research Vol. 14, 5 June 2021, Page 68-79

The variety of recombinant protein expression systems have been developed as a resource of FVII gene expression. In the current study, the authors used a novel protein expression system based on the Iranian Lizard Leishmania, a trypanosomatid protozoan as a host for expression of FVII. Based on the understanding of the role of activated FVII in the treatment of the coagulation disorders, synthesis of recombinant activated FVII (rFVIIa) was considered. Plasmid containing cDNA encoding full-length human FVII was introduced into Lizard Leishmania and positive transfectants were analyzed by SDS-PAGE and Western blot analysis. Furthermore, biological activity of purified protein was detected by PT assay. The recombinant strain harboring a construct was analyzed for expression of FVII at the mRNA and protein level. Purified rFVII was obtained and in order to confirm the purified compound was in fact rFVII. Western blot analysis was carried out. Clotting time in PT assay was reduced about 30 seconds with the purified rFVII. In Conclusion, this study has demonstrated, for the first time, that Leishmania cells can be used as an expression system for producing recombinant FVII.

A 16-year-old female was referred for a pan endoscopy with multiple biopsies for swellings in the nasopharyngeal and paratracheal regions. The patient had bilateral tonsil hypertrophy and grade II MPC with two finger mouth opening and soft tissue swelling compressing the trachea at C4 stage. After intubation patient had resistance to ventilation and desaturation.it was decided to remove tube and hand ventilate patient. After removal of tube, tube was seen to have cuff herniation towards upper end of ETT. The tube was changed, and the rest of the process went without a hitch.

Investigating the Sequence Variation in E2-Binding Domain of HPV16 and Biological Function Evaluation in Tunisian Cervical Cancers

Saloua Kahla, Lotfi Kochbati, Samia Hammami, Mohamed Badis Chanoufi, Mongi Maalej, Ridha Oueslati

Highlights on Medicine and Medical Research Vol. 14, 5 June 2021, Page 85-98

Infection with hr-HPV (High-risk types of the human papillomaviruses) is a necessary but not sufficient cause of invasive cervical cancer, with additional virus-host interactions needed for cancer to develop. HPV16 E2 variants have different effects on the transcriptional activity of the LCR. In this study, we examined the nucleotide and amino acid sequence variation within the HPV16 E2 gene and to correlate with disease progression. E2 gene disruption was detected by PCR amplification of the entire E2 gene using a single set of primers. Nucleotide variations were analyzed by bidirectional sequencing. mRNA expression patterns of E6 and E7 gene transcripts were evaluated by a reverse transcriptase-PCR method (RT-PCR). The detection of intact E2 genes was significantly higher among controls than cases (81.8% versus 37.5%, resp., < 0.05). Among the E subgroup, variation at position 3684 C>A results in the amino acid substitution T310K and was more common among the E2 undisrupted cases (7/9; 77.7%), compared to controls (2/9; 22.2%). In addition, specific sequence variations identified in the E2 ORF at positions 3684 C>A were associated with increased viral oncogenes E6-E7 production. Besides HPV16 E2 disruption, the 3684 C>A variation within undisrupted E2 genes could be involved in an alternative mechanism for deregulating the expression of the HPV16 E6 and E7 oncogenes and appears to be a major factor contributing to the development of cervical cancer in Tunisian women. The study would provide valuable information, as the level of the HPV16 E6-E7 transcripts and the detection of E2 mutations, with DNA physical state detection, could serve as an additional mechanism for evaluating risk for the development of cervical carcinoma.

Studies on Different Techniques of Tympanoplasty: A Historical Review of Indian Perspectives

Manu Malhotra, Saurabh Varshney, Madhu Priya, Abhishek Bhardwaj, Shubhankur Gupta

Highlights on Medicine and Medical Research Vol. 14, 5 June 2021, Page 99-108

Tympanoplasty surgery, which entails the reconstruction of the middle ear hearing apparatus, arose from the basic methods of eardrum repair known as myringoplasty. Reconstructive surgery of the conductive hearing mechanism is collectively called as tympanoplasty, which has gradually evolved over time with the contributions from all over the word.  aim of the present historical review is to summarize the Indian contributions in the development of the technique of tympanoplasty literature review was conducted using only the “Medline” search using keywords “tympanoplasty” and “ossiculoplasty” in “India” on 15th June 2016. A total of 195 articles and abstracts were found dated from the year 1998 onwards. Articles describing work on technique were included, and those describing only experimentation with graft material were excluded. All articles were fully read and analysed. It was found that there had been experiments regarding the choice of anaesthesia and the use of combinations of different chemical agents for this purpose. There were suggestions in favour of monitored anaesthesia care for the surgery in select patients. Surgeons expressed their perspectives on the time and conditions for the surgery, laterality of surgery, different types of incisions, use of endoscopes, graft placement techniques, ossicular replacements with autologous or allogenic grafts, and the timing of prophylactic antibiotic therapy given after or during the surgery.  The range of work is wide and covers most of the aspects of surgery; however, the incorporation of a uniform methodology and standards reporting results were lacking in the articles reviewed. It is recommended that common guidelines for reporting results of tympanoplasty be framed for the Indian sub-continent as a whole. Such an effort will promote uniform reporting standards and hence will become a stable step stone for future analysis and research in the middle ear reconstruction.

Investigating the Loading, Unloading, and Permanent Deformation of Newly Available Epoxy Resin Coated Ni-Ti Wires Using Self-Ligating Brackets

Hazel Garro-Piña, María Cristina Jiménez-Cervantes, Ricardo Ondarza-Rovira, Roberto Justus, Salvador García-López

Highlights on Medicine and Medical Research Vol. 14, 5 June 2021, Page 109-123

Aim: The purpose of this study was to evaluate the load and unload deflection and permanent deformation of round 0.016” and rectangular 0.016” ×0.022” regular and coated Ni-Ti wires. The coated Ni-Ti arch wires present certain disadvantages, this kind of wire continues to be marketed; consequently, new manufacturers are available today.

Materials and Methods: Ni-Ti archwires produced by two manufacturers were evaluated. Both regular and coated round and rectangular Ni-Ti wire segments (n= 15) from each group were submitted to a three-point bending test. Both types of wires were evaluated for permanent deformation at the end of a recovery cycle.

Results: The coated round 0.016” Ni-Ti wires produced a significantly lower force in loading (p< 0.01) and unloading (p< 0.01) than regular wires of the same manufacturer and size. There was no significant difference in permanent deformation between coated and regular round Ni-Ti wires from the same company. For rectangular 0.016×0.022” Ni-Ti wires, there was a significant difference in the loading evaluation, but the unloading test presented no significant differences. The permanent deformation of the rectangular wires revealed no significant difference between them.

Conclusion: The addition of an esthetic coating to these new Ni-Ti wires produced changes in their mechanical properties, manifested as a reduction in the applied force, which should be considered in clinical management.

A Psycho-Cultural Approach to Developmental and Behavioral Pediatrics

Augustin Mubiayi Mamba

Highlights on Medicine and Medical Research Vol. 14, 5 June 2021, Page 124-128

 Talking Pediatrics refers to the welfare of the newborn, taking into consideration his behavior and his development. It is worth to emphasize and mention that we cannot talk of Pediatrics without having a glance to how the mother of the newborn survived the pregnancy period and how the birthchild was handled. These elements play an important role to figure out how the growth of the newborn will be. The development and behavior of a newborn is affected positively or negatively by the behavior of the mother, the one we think does not live in a sole network but in a socio-cultural network which impacts on the birth child, the health of the pregnant woman and the pediatrics considerations in general. A mother, who spent a pregnancy period in harmony with the family (society, environment) is expected to go through well-balanced parturition, in the absentia of infections or programmed complications. This is why a global approach is envisaged in the care to be given to the newborn in order to attain successful pediatrics management. Let us consider a nutrition aspect picking the case of breast-feeding, for example. We may notice that, not only the milk that comes out of the mother’s breast is crucial for the baby. On a psychological point of view, the fact that a baby remains in the chest of the mother, sucking the breast even if no milk is coming out, increases the attachment and the affectivity of the newborn to the mother. This is an expression of libido of Sigmund Freud. While advising and campaigning on the breastfeeding for a newborn, the emphasis should not be put only on the chemical or biological nutriment but also on the psychic nutriment, which contribute to the total care and development of this newborn and build his behavior tomorrow. In our research on psychological accompaniment to complicated childbirth’s, we considered the problem of childbirth as a node containing several facets, which facets could be treated in synergy between several specialties. It is this holistic view of the problem that, amongst other things, has led us to believe that the mother as well as the newborn does live not in a social and cultural vacuum, but rather in a network of social and cultural relations. This society waits from the newborn, in terms of potential, will occupy status and plays roles in this society and change the environment. We believe that culture plays a proper role in the development and behavior of the newborn, future adult.

The Effect of Short-term Creatine Supplementation Suppresses the Cortisol Response to a High-Intensity Swim-Sprint Workout

V. Dobgenski, M. G. Santos, B. Campbell, R. B. Kreider

Highlights on Medicine and Medical Research Vol. 14, 5 June 2021, Page 129-136

The primary aim of t he present study was to evaluate the effects of creatine ingestion on the metabolic hormone cortisol in male swimmers. Seventeen male swimmers (24.5 ± 3.9 years) with at least 5 years of competitive swimming experience and engaged in swimming training at least 4 times per week participated in t he study. Subjects supplemented with creatine (20 g/day) + maltodextrin (1 g/kg/day) or maltodextrin (1 g/kg/day) only for 6 days prior to a progressive swim-sprint workout. The swim-sprint workout consisted of 8 progressive 100 meter freestyle sets starting at 65% of maximal intensity leading up to a 100% maximum capacity set on the eighth and final set. Cortisol was assessed immediately before and immediately after (within 5 minutes) the swim-sprint workout. After 6 days of creatine monohydrate supplementation, there was a significant reduction in cortisol concentrations following the progressive swim-sprint workout in the creatine + maltodextrin group (15.5 ± 0.99 \(\mu\)g/dL) as compared to the maltodextrin only group (18.33 ± 2.61 \(\mu\)g/dL). Based on these findings, it appears that creatine loading (20 grams per day for 6 days) significantly reduces the cortisol response to 100-meter freestyle swimming sets performed in a progressive intensity manner. This finding may be beneficial for athletes undergoing intense training and may help prevent overtraining syndrome and assist the athlete in a more rapid recovery post-exercise.