Functional characterization of transcriptional activator gene SIARRI in tomato reveals its role in fruit growth and ripening.

Auxins regulate several characteristics of plant development and growth. Here, we characterized a new transcriptional activator SIARRI which binds specific DNA sequences and was revealed in Arabidopsis (ARR1). SIARRI acts as a two-component response regulator and its Arabidopsis homologous gene is AT3G16857. It belongs to the subfamily of type-B response regulators in the cytokinin signaling pathway. The study aimed to characterize the transgenic Micro-Tom plants by the overexpression of Solanum lycopersicum two-component response regulator ARR1. Overexpression of SIARRI results in a pleiotropic phenotype during fruit development and ripening. This study indicates that SIARRI is a primary regulator of leaf morphology and fruit development. Moreover, overexpressed plants showed variations in growth related to auxin as well as shorter hypocotyl elongation, enlarged leaf vascularization, and decreased apical dominance. The qRT-PCR investigation revealed that expression was downregulated at the breaker stage and high at Br+6 at various stages of fruit growth and ripening. In contrast to the fruit color, lycopene and ß-carotene concentrations in red-yellow overexpression line fruits were reduced significantly, and also slightly reduced in some red fruits. The quantity of ß-carotene in the transgenic fruits was lower than that of lycopene. This study showed that this gene might be a new transcriptional activator in fruit development and ripening. Furthermore, this study will provide new insights into tomato fruit ripening.

Frequency of Subclinical Hypothyroidism in Patients With Chronic Kidney Disease.

INTRODUCTION:  Chronic kidney disease (CKD) is the progressive loss of function of the nephron over a long period of time. As the glomerular filtration rate falls, it leads to subclinical hypothyroidism (SCH). This cross-sectional study is carried out to measure the frequency of SCH in CKD patients in our population. METHODS: This case-control research was undertaken at the nephrology unit of the Peoples University of Medical and Health Sciences for Women in Pakistan from March 2021 to January 2022. The research included 200 volunteers with documented evidence of CKD between the ages of 18 and 60 years. A case group of 200 people without CKD was also enlisted, matched by age, gender, and comorbidities. Data were recorded in a self-structured questionnaire and analyzed using Statistical Package for the Social Sciences® software (IBM Corp., Armonk, NY). RESULTS:  Thyroid-stimulating hormone was significantly raised in participants with CKD (4.91 ± 1.10 mIU/L vs. 3.62 ± 0.72 mIU/L; p-value < 0.0001). A significant association between SCH and CKD was established (p-value < 0.00001). CONCLUSION:  Due to the positive correlation between SCH and CKD, multidisciplinary management, including a team of endocrinologists and nephrologists, is advised to keep a regular check on these patients.

Long-Term Symptoms of COVID-19: One-Year Follow-Up Study.

INTRODUCTION:  Persistent and prolonged symptoms, termed as long COVID (coronavirus disease), have been reported in several patients who recovered from the acute phase at different intervals. However, there has been largely unclear data regarding the full range of long-term sequelae of coronavirus disease 2019 (COVID-19) patients. This study aims to evaluate the prevalence of long COVID syndrome. METHODS: A long-term research was conducted in the COVID-19 unit of a tertiary care hospital in Pakistan from July 2020 to December 2021 in which 2,000 patients who had recovered from COVID-19 and had been discharged were included in the study. Symptoms were noted at the time of discharge and at follow-up after 12 months. Data were analyzed using Statistical Package for the Social Sciences (SPSS) v. 22.0 (IBM Corporation, Armonk, New York, United States). RESULTS: The mean age of the participants was 43 ± 10 years, 801 (53.8%) males and 688 (46.2%) females. At the time of discharge, the most common symptom was fatigue (26.93%), followed by dyspnea (20.34%) and muscle pain (8.86%). The most common symptom on follow-up was fatigue (6.78%). CONCLUSION: We strongly emphasize discussing and exploring further knowledge on the post-infection syndrome, with an aim to bring healthcare professionals' attention to the importance of handling COVID patients, their counseling, warning for alarming signs, and a long-term follow-up with necessary investigations and treatment.

Frequency of Causes of Portal Hypertension in Children.

Introduction The most common etiology of portal hypertension (PH) in children is obstruction at the presinusoidal or sinusoidal level. In addition, portal vein thrombosis (PVT) and biliary atresia are the most prevalent extrahepatic causes. This study aims to evaluate all the possible etiologies leading to PH in the pediatric population and provide the most common cause associated with this condition along with the age group most frequently affected by it. Material and Methods From January 2018 to December 2020, a cross-sectional study was carried out in tertiary care hospitals in Pakistan. A total of 100 children, both male and female, aged one month to 15 years and diagnosed with PH, were enrolled for the evaluation for the causes of PH. The Statistical Package for the Social Sciences (SPSS), version 20, was used to analyze the data. Results The mean age of enrolled participants was 9.01 ± 2.81 years. It was found that PVT (63%) was the most common cause of PH, followed by liver cirrhosis (19%) and biliary atresia (18%). Age of more than eight years was significantly associated with PVT (p-value: 0.007). Conclusion In children, PH may be caused by a wide range of etiologies. It is imperative to understand the underlying etiologies contributing to PH for proper guidance and management, prevention, and overall outcomes.

Sorptive removal of diamond green dye by acid treated Punica granatum peels in eco-friendly way.

In this study, acid treated Punica granatum (PG) peels were used for effective removal of Diamond green (DG) dye, commonly found in textile industry waste. Acid treatment enhanced the efficiency of this process along with increasing shelf life and stability of bio-adsorbent by reducing fungal attack risk. Optimized operational parameters for removing DG dye using PG peels powder were: 35-minute contact time, 75 rpm agitation speed, 50°C temperature and pH of 2. Isothermal study results showed that maximum dye removing capacity was 29.08 mg/g. ΔG and ΔH values were -6.384 and -0.05 kJ/mol, respectively indicating that DG dye adsorption on acid treated PG peels is spontaneous and exothermic in nature. It was found that for batch scale adsorptive removal of basic dyes like DG, acid treated Punica granatum peels were effective bio-waste that can be used from our indigenous sources in an effective way.

Role of Cod Liver Oil in Preventing Myocardial Infarction.

INTRODUCTION: Omega-3 fatty acids have for long been shown to reduce the incidence of cardiovascular (CV) diseases. Omega-3 fatty acids mainly exist in the form of eicosapentaenoic acid (EPA) and docosahexaenoic acid in fish oils. Cod liver oil is found to have a high concentration of these omega-3 fatty acids. This study aims to explore the benefits of using cod liver oil in reducing the incidence of myocardial infarction (MI) among at-risk patients.  Method: This open-label placebo-controlled two-arm interventional study was conducted in the internal medicine and cardiology unit of tertiary care hospital between January 2018 to January 2021. During this period, 870 patients at risk of CV events were enrolled in the study after obtaining informed consent. The study group received 415 mg cod liver oil daily, in addition to their current treatment, in a bottle without label and the control group received no additional treatment to their standard treatment. Patients were followed up for 12 months or till the development of MI. RESULT: Patients treated with cod liver oil had comparatively fewer incidences of MI; however, the difference was not significant (p-value: 0.09). Furthermore, the difference was non-significant for both fatal and non-fatal MI. The relative risk for total MI incidence was 0.70 (0.44-1.10). CONCLUSION: According to our study, adding cod liver oil to the diet does not play a major role in reducing the risk of MI. Further large-scale studies are needed to understand the role of cod liver oil in reducing the risk of CV events, including MI.

Impact of Asthma on the Quality of Sleep in Young People.

Introduction Asthma has a negative impact on the quality of life of patients and their families. One of the factors responsible for the low quality of life is poor sleep quality in asthmatic patients. Sleep disturbances, such as difficulty initiating and maintaining sleep, are common in asthma. In this study, we aim to determine the quality of sleep in young asthmatic patients in a local setting. Method This case-control study was conducted in the pulmonology and internal medicine unit of a tertiary care hospital, Pakistan from January 2021 to May 2021. After seeking informed consent, 200 patients with a previously confirmed diagnosis of asthma were enrolled in the study. The control group also included 200 participants. Pittsburgh Sleep Quality Index (PSQI) is an efficient measure of the quality and pattern of sleep. A global PSQI score of ≥5 signifies "poor sleep quality." Results The mean PSQI score was significantly higher in the asthmatic group compared to the control group (6.26 ± 2.01 vs. 3.41 ± 0.50; p-value: <0.0001). The percentage of participants with a PSQI score of ≥5 was significantly higher in the asthmatic group compared to the control group (54.5% vs. 17.0%; p-value: <0.0001). Conclusion Sleep disturbance is very common in young patients with asthma. Poor sleep may interfere with their daily performance, which may further have a negative impact on the quality of life in asthmatic patients. Management of asthma should also include improving sleep quality.

Causes of Acute Peritonitis and Its Complication.

Introduction Peritonitis is a significant cause of morbidity and mortality in surgical settings. Coexisting premorbid illness and postoperative complications were found to be associated with death. This study aimed to analyze various etiologies that cause peritonitis and shed light on the factors responsible for unsatisfactory results. Method This longitudinal study included 309 patients above 12 years of age, of either gender, with confirmed diagnosis of peritonitis. Exploratory laparotomy was done to identify the cause of peritonitis. Patients were monitored postoperatively till their discharge or death for the development of complications. Results Our results showed that the most common cause of acute peritonitis was duodenal perforation (26.2%), followed by typhoid ileal perforation (24.2%) and ruptured appendix (16.8%). At least one complication was observed in 31% of the participants. The most common complication was dehydration (18.8%), followed by septicemia (11.3%) and paralytic ileus (6.4%). Ten (3.2%) patients died in the hospital. Conclusions Acute peritonitis is a serious surgical emergency caused by a number of diseases. Early surgical treatment along with antibiotics, followed by aggressive resuscitation can yield improved outcomes in patients with peritonitis.

Prevalence and Causes of Hyperuricemia in Children.

Introduction  There are various factors responsible for hyperuricemia in children, however, there is extremely limited local data available. In this study, we aim to determine the causes and risk factors associated with hyperuricemia. This study will assist pediatric consultants to identify children who might be at risk of hyperuricemia and manage them accordingly. Methods This study was conducted in pediatric outpatient departments of various tertiary care hospitals from January 2018 to December 2019. Five thousand (n = 5000) children of either gender between the age group of 1-14 years, were enrolled in the study after informed consent from their parents. Uric acid levels were assessed by using the UASure blood uric acid monitoring handheld device. Results  In our study, n = 1301 (26.02%) children had hyperuricemia. Hyperuricemia was more common in male compared to females (65.49% vs. 34.51%; p-value <0.00001) and in older children (9 ± 2 years vs. 7 ± 3; p-value <0.00001). In hyperuricemia patients, the most common disorder was gastroenteritis (23.98%), followed by respiratory infection (23.14%) and asthma (15.45%). Conclusion  Hyperuricemia in children is very prevalent in the local setting. Patients with pre-existing conditions like congenital heart disease, asthma, epilepsy, and cancers should routinely be screened for hyperuricemia and managed accordingly to avoid long-term complications associated with hyperuricemia.

Lumbar Disc Herniation: Comparing Pain Relief After Medical and Surgical Intervention.

Introduction The most common degenerative abnormality of the lumbar spine is lumbar disc herniation. There are two options of treatment, i.e. medical and surgical. Due to the scarcity of literature, it is a need of the hour to further study and evaluate the benefits and efficacy of early surgical intervention versus conservative management of lumbar disc herniation. Methods This study was conducted in the neurology unit of a tertiary care hospital in Pakistan from April 2019 to March 2021. After obtaining informed consent, 250 patients with a lumbar disc herniation, between the ages of 20 and 50 years, were enrolled in the study. Out of them, 81 participants chose surgical intervention while 169 participants chose medical intervention. Before the intervention, the patient's pain score was noted on the visual analog scale (VAS). The pain was assessed again 14 days after surgical intervention and 90 days after the start of medical intervention. Results There was a significant difference in the pain score in the post-intervention period in both the medical (7.01 ± 1.05 vs. 3.54 ± 0.51; p-value: <0.0001) and surgical intervention groups (6.92 ± 0.95 vs. 2.41 ± 0.42; p-value: <0.0001). Post-intervention, the VAS pain score was significantly lower in the surgical group as compared to the medical group (2.41 ± 0.42 vs. 3.54 ± 0.51; p-value: <0.0001). Conclusion In this study, there was a significant decline in pain in both groups; however, the reduction was more significant in the surgical group. Patients should be given both options for management of lumbar disc herniation and should be explained the pros and cons of each treatment option.

Association of Low Magnesium Level With Duration and Severity of Type 2 Diabetes.

INTRODUCTION: Type 2 diabetes mellitus can give rise to several complications in the body, including electrolyte imbalance. In this study, we aim to find the association of hypomagnesemia with the duration and severity of diabetes. Understanding the association between magnesium and diabetes may assist in the early detection of hypomagnesemia and help manage the complications associated with electrolyte imbalance. METHODS: This cross-sectional study was conducted in the internal medicine department of a tertiary care hospital in Pakistan from January to March 2021. Three hundred (n = 300) patients with a confirmed diagnosis of type 2 diabetes were enrolled in the study after informed consent via consecutive convenient non-probability sampling. Three hundred (n = 300) patients were included in the study as a reference group. Blood was drawn via phlebotomy and sent to the laboratory to assess glycated hemoglobin (HbA1c) and magnesium levels. RESULTS: In uncontrolled diabetic patients, mean magnesium level was significantly lower as compared to diabetic patients with good glycemic control (1.34 ± 0.3 mg/dL vs. 1.81 ± 0.5; p-value: <0.0001). Prevalence of hypomagnesemia was significantly more in patients with uncontrolled diabetes, compared to the controlled diabetic group (65.8% vs. 50.8%; p-value: 0.009). In patients with a duration of diabetes of more than 10 years, the mean magnesium level was significantly lower, compared to patients with less than 10 years of diabetes (1.32 ± 0.3 mg/dL vs. 1.78 ± 0.5; p-value: <0.0001). Prevalence of hypomagnesemia was significantly more in patients with diabetes for more than 10 years (64.7% vs. 51.9%; p-value: 0.02). CONCLUSION: Hypomagnesemia is prevalent in diabetes and is directly related to the severity and duration of diabetes. It is important to include electrolyte screening as a part of routine screening in diabetic patients for early detection and management of electrolyte imbalance, including hypomagnesemia.

Gastroesophageal Reflux Disease in the Young Population and Its Correlation With Anxiety and Depression.

Introduction Stress and anxiety may disrupt normal GI function and lead to several GI disorders, including gastroesophageal reflux disease (GERD). In this study, we aimed to predict the prevalence of GERD in young patients and its association with anxiety and depression. Material and Methods This cross-sectional study enrolled 2,500 participants from the general public, with an age range of 18 to 40 years. Diagnosis of GERD was made via the Frequency Scale for the Symptoms of GERD (FSSG) questionnaire. The Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depression. Results GERD was diagnosis in 401 (16.0%) participants. Anxiety was significantly more common in participants with GERD compared to participants without GERD (40.3% vs. 19.5%; p < 0.01). Similarly, participants with GERD had a higher prevalence of depression compared to participants without GERD (42.6% vs. 18.3%; p < 0.01). Conclusion GERD is highly prevalent among the young population. Anxiety and depression are significantly more prevalent in patients with GERD. Hence, the young population must be thoroughly screened for GERD to minimize the risk of long-term complications. Furthermore, patients diagnosed with GERD should be screened for depression and anxiety.

Pulmonary Manifestations of Inflammatory Bowel Disease.

The frequency of extraintestinal manifestations of inflammatory bowel disease (IBD) is observed in most of the patients. Extraintestinal manifestations of IBD have been implicated in all the anatomic sites of the pulmonary tree, and include airway inflammation of the bronchi and bronchioles and parenchymal inflammation. There is a wide range of pulmonary manifestations in IBD, and most of them look a lot like other diseases. Doctors should keep a track of these conditions to avoid unnecessary complications and to provide an early diagnosis with correct and efficient treatment. IBD-related respiratory disorders are treated depending on the patient, but in most of them, steroids are generally chosen first. Steroids, both inhalational and systemic, are the primary approach. Antibiotics could also be given if the patient has infections or suppuration, usually followed by surgeries. However, drug-induced complications and toxicity should be kept in mind.

CRISPR-Cas System: History and Prospects as a Genome Editing Tool in Microorganisms.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR or more precisely CRISPR-Cas) system has proven to be a highly efficient and simple tool for achieving site-specific genome modifications in comparison to Zinc Finger Nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs). The discovery of bacterial defense system that uses RNA-guided DNA cleaving enzymes for producing double-strand breaks along CRISPR has provided an exciting alternative to ZFNs and TALENs for gene editing & regulation, as the CRISPR-associated (Cas) proteins remain the same for different gene targets and only the short sequence of the guide RNA needs to be changed to redirect the site-specific cleavage. Therefore, in recent years the CRISPR-Cas system has emerged as a revolutionary engineering tool for carrying out precise and controlled genetic modifications in many microbes such as Escherichia coli, Staphylococcus aureus, Lactobacillus reuteri, Clostridium beijerinckii, Streptococcus pneumonia, and Saccharomyces cerevisiae. Though, concerns about CRISPR-Cas effectiveness in interlinked gene modifications and off-target effects need to be addressed. Nevertheless, it holds a great potential to speed up the pace of gene function discovery by interacting with previously intractable organisms and by raising the extent of genetic screens. Therefore, the potential applications of this system in microbial adaptive immune system, genome editing, gene regulations, functional genomics & biosynthesis along ethical issues, and possible harmful effects have been reviewed.

Evaluation of the role of maternal serum high-sensitivity C-reactive protein in predicting early pregnancy failure.

Maternal serum high-sensitivity C-reactive protein (HSCRP) was evaluated in predicting spontaneous abortion in spontaneous pregnancies presenting with threatened spontaneous abortion. Seventy-one cases of threatened spontaneous abortion (group A) and 71 asymptomatic controls (group B), matched for gestational and maternal age, body mass index and smoking status, were included. Maternal serum samples were evaluated for HCG, progesterone, pregnancy-associated plasma protein-A (PAPP-A) and HSCRP using standard bio-assays. No difference was observed in ultrasound measurements, and median progesterone maternal serum level was significantly lower (P < 0.05) in group A compared with group B. In group A, the median of all ultrasound and maternal serum parameters was significantly lower (P < 0.01) compared with group B. The median gestational sac diameter, volume and median HSCRP and PAPP-A levels were significantly increased (P < 0.05) in group A, with a normal outcome compared with group B, probably owing to the inflammatory reaction associated with intrauterine bleeding. In group A patients destined to abortion, the gestational sac development and corresponding protein synthesis fell before the fetal heart activity stopped; in spontaneous pregnancies, maternal serum HSCRP did not provide additional information for the management of threatened spontaneous abortion but warrants further research in assisted reproduction pregnancies.

Oxygen-linked S-nitrosation in fish myoglobins: a cysteine-specific tertiary allosteric effect.

The discovery that cysteine (Cys) S-nitrosation of trout myoglobin (Mb) increases heme O2 affinity has revealed a novel allosteric effect that may promote hypoxia-induced nitric oxide (NO) delivery in the trout heart and improve myocardial efficiency. To better understand this allosteric effect, we investigated the functional effects and structural origin of S-nitrosation in selected fish Mbs differing by content and position of reactive cysteine (Cys) residues. The Mbs from the Atlantic salmon and the yellowfin tuna, containing two and one reactive Cys, respectively, were S-nitrosated in vitro by reaction with Cys-NO to generate Mb-SNO to a similar yield (∼0.50 SH/heme), suggesting reaction at a specific Cys residue. As found for trout, salmon Mb showed a low O2 affinity (P50 = 2.7 torr) that was increased by S-nitrosation (P50 = 1.7 torr), whereas in tuna Mb, O2 affinity (P50 = 0.9 torr) was independent of S-nitrosation. O2 dissociation rates (koff) of trout and salmon Mbs were not altered when Cys were in the SNO or N-ethylmaleimide (NEM) forms, suggesting that S-nitrosation should affect O2 affinity by raising the O2 association rate (kon). Taken together, these results indicate that O2-linked S-nitrosation may occur specifically at Cys107, present in salmon and trout Mb but not in tuna Mb, and that it may relieve protein constraints that limit O2 entry to the heme pocket of the unmodified Mb by a yet unknown mechanism. UV-Vis and resonance Raman spectra of the NEM-derivative of trout Mb (functionally equivalent to Mb-SNO and not photolabile) were identical to those of the unmodified Mb, indicating that S-nitrosation does not affect the extent or nature of heme-ligand stabilization of the fully ligated protein. The importance of S-nitrosation of Mb in vivo is confirmed by the observation that Mb-SNO is present in trout hearts and that its level can be significantly reduced by anoxic conditions.

Soluble Flt-1 and PlGF: new markers of early pregnancy loss?

Recent data have indicated a relationship between placental oxygen and angiogenic protein levels in the first trimester of normal pregnancies. Our objective was to investigate if maternal serum levels of angiogenic factors Soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1), soluble Endoglin and placental growth factor (PlGF) are altered in women with symptoms of threatened miscarriage (TM) and if they are predictive of a subsequent miscarriage. Blood samples were collected at 6-10 weeks from women presenting with TM (n = 40), from asymptomatic controls (n = 32) and from non- pregnant women in their luteal phase (n = 14). All samples were assayed for serum level of sFLT-1, PlGF, sEndoglin and HSP70 using commercial ELISAs. Samples were analysed retrospectively on the basis of pregnancy outcome. TM group included 21 women with a normal pregnancy outcome and 19 with subsequent complete miscarriage. The latter subgroup had significantly lower mean maternal serum (MS) sFlt-1 (83%, P<0.001) and PlGF (44%, P<0.001) compared to those with a normal pregnancy outcome. Asymptomatic control pregnant women had similar MS levels of sFlt-1 and PlGF compared to the TM patients with a normal outcome. The mean MS sFlt-1 (>10 fold) and MS PlGF (∼2 fold) levels were significantly (P<0.001) higher in control pregnant women compared to the non-pregnant group in the luteal phase of the menstrual cycle. Soluble Endoglin was not altered in the normal pregnant women compared to non pregnant women, although lower in the TM subgroup with a subsequent miscarriage (∼25%, P<0.001) compared to TM with a live birth. There was no significant difference in the mean MS HSP 70 levels between the different groups. This study shows that sFlt1 and PlGF MS levels are increased by several folds in early pregnancy and that MS sFlt-1 and MS PlGF are markedly decreased in threatened miscarriage patients who subsequently have a miscarriage suggesting these proteins are sensitive predictive markers of subsequent pregnancy loss.