Thyroid surgery in children: a single-center experience of 20 years

SUMMARY OBJECTIVE: Thyroidectomy is a relatively uncommon procedure in pediatric patients. We aimed to review our 20-year experience of thyroid surgery. METHODS: A total of 39 patients who underwent thyroid surgery from 2003 to 2023 were retrospectively evaluated. All patients were followed preoperatively and postoperatively by our institutional multidisciplinary board. Patients were divided into two groups based on their pathologies: benign and malignant. RESULTS: In total, 39 patients (27 girls and 12 boys) underwent 47 thyroid surgeries (total thyroidectomy in 19 patients and subtotal thyroidectomy in 20 patients, with 8 of them having completion thyroidectomy). Notably, 20 (51%) patients had benign and 19 (49%) patients had malignant pathologies. Median age at operation was 157 (9-223) months in the benign group and 182 (1-213) months in the malignant group. In the benign group, 12 (60%) patients had colloidal goiter and 8 (40%) patients had other conditions. In the malignant group, 12 (63%) patients had papillary thyroid carcinoma, 3 (16%) patients had follicular thyroid carcinoma, 2 (11%) had medullary thyroid carcinoma, and 2 patients had other thyroid malignancies. Overall permanent complication rate was 2 out of 39 (5%), which was similar for both groups (1 hypocalcemia in each group). The median follow-up was 38 months (1-179 months) with no local recurrence or distant metastasis. CONCLUSION: Pediatric thyroidectomies are performed on a heterogeneous group of pediatric patients due to a diverse group of pathologies. A multidisciplinary approach is required for proper initial management and surgical strategy with decreased complication rate and event-free survival of these patients in experienced tertiary centers.

Crystal storing histiocytosis forming a mass lesion in temporal lobe

Crystal storing histiocytosis is a disorder characterized by local or diffuse infiltration of histiocytes containing crystalline inclusions. This entity has been reported in several organs, however the involvement of the central nervous system (CNS) is extremely rare and to date only 7 cases of crystal storing histiocytosis (CSH) of CNS have been reported in the English literature. More than 90% patients with CSH had an underlying lymphoproliferative or plasma cell disorders, especially multiple myeloma, lymphoplasmacytic lymphoma or monoclonal gammopathy. Radiologically and intraoperatively, CSH may mimic an infectious process or neoplasm, hence its histopathological confirmation is important to facilitate appropriate treatment. In this report, we describe an additional case of crystal storing histiocytosis in a 48 year old female who presented with a mass lesion in the right temporal lobe of the cerebrum.

Effect of learning curve on the perioperative course of robotic-assisted laparoscopic donor nephrectomy compared with laparoscopic donor nephrectomy

Summary OBJECTIVE: This study was designed to compare the standard and robotic-assisted laparoscopic donor nephrectomy in terms of perioperative course, short-term postoperative outcome, and to evaluate the effect of surgeon's learning curve on these parameters. METHODS: This was a prospective randomized study including 60 patients (mean age, 47 years; age, 21-72 years; 26 males, 34 females) who had been planned laparoscopic donor nephrectomies in our clinic. For comparison of standard and robot-assisted techniques and to evaluate the impact of learning curve, patients were randomized into three groups by a computer, each group containing 20 patients. Group 1: standard laparoscopic donor nephrectomies; Group 2: the first 20 patients who underwent robot-assisted laparoscopic donor nephrectomy; and Group 3: the next 20 patients who underwent robot-assisted laparoscopic donor nephrectomy. RESULTS: Operative time was significantly higher in Group 2 (221.0±45.1 min) than both Group 1 (183.5±16.9 min, p=0.001) and Group 3 (186.5±20.6 min, p=0.002). Similarly, time for laparoscopic system setup was significantly higher in Group 2 (39.5±8.6 min), which contained the first cases of robot-assisted laparoscopic donor nephrectomy where surgeon had least experience than Group 1 (19.3±3.7 min, p<0.001) and Group 3 (24.0±9.4 min, p<0.001). On the other hand, duration of operation and time for laparoscopic system setup was similar between Groups 1 and 3. CONCLUSIONS: Learning curve extends the operative time and laparoscopic system setup time in robotic-assisted laparoscopic donor nephrectomy, however, after the learning process was completed, these parameters were similar between robotic-assisted and standard laparoscopic nephrectomy.

Role of calcium-sensing receptor, Galectin-3, Cyclin D1, and Ki-67 immunohistochemistry to favor in the diagnosis of parathyroid carcinoma

Background: As histopathological findings of parathyroid carcinoma are not certain, the diagnosis of tumors with degenerative changes may be difficult. In these cases, immunohistochemical markers are beneficial. We aimed to research the acceptability of calcium-sensing receptor (CaSR), Galactin-3, Cyclin D1, and Ki-67 as helpful markers in parathyroid tumors in cases which are difficult to diagnose. Materials and Methods: Those cases who had been diagnosed with atypical parathyroid adenoma and parathyroid carcinoma between 2010 and 2015 were reevaluated. ?mmunohistochemical markers were applied to this cases. Results: About 21 cases were parathyroid adenoma, 14 were atypical adenoma, and 10 cases were parathyroid carcinoma. According to the immunohistochemical results, global loss of CaSR staining was seen in 50% (5/10) of the patients with carcinoma while there was no loss of staining in those with parathyroid adenoma (P = 0,001). Global loss of CaSR staining was found in only one out of 14 cases with atypical adenoma. The expression of Galactin-3 was found to be positive in 40% (4/10) of carcinoma cases, 71.4% (10/14) of those with atypical adenoma, and 14.3% (3/21) of those with adenoma (P = 0,002). Cyclin D1 expression was determined to be positive in 70% (7/10) of patients with carcinoma, 71.4% (10/14) of atypical adenoma cases, and 23.8% (5/21) of those with adenoma. The Ki-67 proliferation index was seen to be above 5% in 50% (5/10) of carcinoma cases and 35,7% (5/14) of those with atypical adenoma. Conclusion: In these studies, it has been emphasized that the global loss of CaSR staining was used as a negative marker in the diagnosis of carcinoma. In this study, we have also confirmed that the global loss of CaSR staining is a useful marker to determine potential increased malignancy.

Effect of Enrofloxacin on the Joint Fluid/Blood Oxidative Status and Organ Damage Markers

Aim: It has been hypothesized that chondrotoxicity, the main side effect of enrofloxacin use, may be derived from oxidative stress, and this side effect can be confirmed by measuring malondialdehyde and endogen antioxidants following drug application. The primary aim of this research is to determine the effect of enrofloxacin on the joint fluid and blood oxidative status parameters, and it is also to determine the effect on the organ damage parameters. Materials and Methods: In the study, 10 rams received enrofloxacin (10 mg/kg/day, SC) for 14 days. Blood and joint fluids were taken on day 0 (Control) before drug application and 1.5 hours after the last drug application. Plasma and joint fluid malondialdehyde, total antioxidant status, superoxide dismutase, glutathione peroxidase and catalase levels were determined by an ELISA reader. Cardiac (CK-MB mass, troponin I), liver (AST, ALT, ALP, GGT, total protein, albumin) and kidney (Creatinine, BUN) damage markers and hemogram (WBC, RBC, platelet, hematocrit, haemoglobin) values were measured. Results: Enrofloxacin decreased the joint fluid catalase level (P<0.05), while there was no effect observed in the other oxidative status parameters of joint fluid or blood samples. Statistically significant changes (P<0.05) were found in some hemogram and biochemical parameters within the reference range. However, enrofloxacin increased (P<0.05) the levels of cardiac damage markers (CK-MB mass, troponin I). Conclusion: It may be stated that enrofloxacin does not cause oxidative stress in the joint fluid and blood in rams, and it is generally accepted to be safe when the effect on the organ/system is considered, but the long-term use and high doses require caution in terms of possible heart related damage.

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis / O papel potencial da amlodipina na rinossinusite bacteriana induzida experimentalmente

Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

Resumo Introdução: Antibióticos são frequentemente usados para o tratamento de rinossinusite. Questões têm sido levantadas sobre os efeitos adversos dos antibióticos e a resistência crescente. A falta de desenvolvimento de novos compostos antibióticos aumentou a necessidade da exploração de compostos não antibióticos que têm atividade antibacteriana. A amlodipina é um composto não antibiótico com atividade anti-inflamatória. Objetivo: O objetivo desse estudo foi investigar o papel potencial da amlodipina no tratamento da rinossinusite, avaliando seus efeitos sobre o estado oxidativo do tecido, histologia da mucosa e inflamação. Método: Quinze cobaias albinas adultas foram inoculadas com Staphylococcus aureus e tratadas com solução salina, cefazolina ou amlodipina durante sete dias. O grupo controle incluiu cinco cobaias saudáveis. Os animais foram sacrificados após o tratamento. Alterações histopatológicas foram identificadas com a coloração de hematoxilina-eosina. A inflamação foi avaliada pela densidade de infiltração de leucócitos polimorfonucleares. Foram determinados os níveis teciduais de antioxidantes (superóxido dismutase, glutationa) e um produto de oxidação (malondialdeído). Resultados: Em animais com rinossinusite induzida, a amlodipina reduziu a perda dos cílios, edema da lâmina própria e deposição de colágeno em comparação com o grupo placebo (solução salina) e embora não seja superior à cefazolina, a amlodipina diminuiu a infiltração de leucócitos polimorfonucleares. Os níveis de atividade da superóxido dismutase e glutationa foram reduzidos, enquanto os níveis de malondialdeído aumentaram significativamente nos três grupos de tratamento em comparação ao grupo controle. O grupo tratado com amlodipina apresentou aumento significante dos níveis de superóxido dismutase e glutationa e diminuição dos níveis de malondialdeído em comparação com todos os grupos de tratamento. Conclusão: O composto não antibiótico amlodipina pode ter um papel no tratamento da rinossinusite aguda através de mecanismos protetores de tecido, antioxidantes e anti-inflamatórios.

Investigation of anti-proliferative and antioxidative effects of some bis [alpha-amino] phosphinic acid derivatives

Aminophosphinic acids which are organophosphorus compounds widely investigated for potential production of antibacterial, antitumor and antiviral materials. In vitro antioxidant, cytotoxic and antimicrobial activities of synthesized novel compounds of 8 different bis[alpha-amino alkyl]phosphinic acids [4a-h] were investigated on MCF-7 breast adenocarcinoma cell and human umbilical vein endothelial cell [HUVEC] cultures. Malondialdehyde [MDA] levels were evaluated as an indication of lipid peroxidation in cell cultures for antioxidant capacities. In vitro antioxidant activities in cell cultures were determined by evaluating totals of antioxidant, oxidant, thiol levels and activities of paraoxanase, aryl esterase. It was found that 4c compound reduced MDA level significantly while 4a and 4g compounds increased MDA levels significantly compared to control. 4c compound was found most effective in reducing MDA levels by neutralizing reactive oxygen species to prevent cell damage while compounds 4c, 4f and 4h were found presenting adequate activity with other antioxidants. In vitro anti-proliferation was evaluated on MCF-7 and HUVEC cells using XTT to investigate anti-cancer potentials as therapeutics. Compounds 4c, 4e and 4f were exhibited better compared to others. Most compounds were found cytotoxic to both MCF-7 and HUVECs. Antimicrobial and antifungal activities were investigated by disc diffusion and compared to MICs of Gentamycin and Nystatin

Bone marrow radiation dosimetry of high dose [131]I treatment in differentiated thyroid carcinoma patients

Background: Radiation absorbed dose to the red bone marrow, a critical organ in the therapy of thyroid carcinoma, is generally kept below 2 Gy for non-myeloablative therapies. The aim of this study was to calculate bone marrow radiation dose by using MIRDOSE3 package program and to optimize the safe limit of activity to be administered to the thyroid cancer patients. Materials and Methods: In this study, 83 thyroid cancer patients were divided into 3 groups based on the amount of activity administered into the body. In the groups, 3700 MBq, 5550 MBq and 7400 MBq activities were used respectively. The curves of time-activity were drawn from blood samples counts and effective half-life and residence time were calculated. Correlations of bone marrow radiation dose and radioiodine effective half-life were determined as a function of administered activity via ANOVA test. Tg levels and tumour diameters were compared using Spearman's correlation. Results: The effective half-lives of [131]I for three groups of whole-body, receiving 3700 MBq, 5550 MBq and 7400 MBq were calculated as 20.57+/-5.4, 17.8+/-5.8 and 18.7+/-3.9 hours, respectively. The average bone marrow doses for 3 groups of patients were 0.32+/-0.08 Gy, 0.42+/-0.14 Gy and 0.60+/-0.24 Gy, respectively. Conclusion: It was concluded that, the bone marrow dose to the patients still remains within the recommended level even after administering an activity of 7400 MBq of [131]I to the patients

rare location: a giant mesenteric lipoma

Lipomas are benign soft tissue tumors. They can rarely be mesenterically located and symptomatic. It is very important to conduct the differential diagnosis of large intra-abdominal mass lesions. Radiological imaging techniques are often used for diagnosis, but when these techniques are not sufficient or when it becomes obligatory to cure symptoms of the lesion, surgical excision should be performed. This study aimed to present a patient with complaints and symptoms of an intra-abdominal giant mass lesion, the pathological diagnosis of which the revealed a giant mesenteric lipoma

Serum beta-defensin-2 levels and their relationship with the clinical course and prognosis in patients with crimean-congo hemorrhagic fever

Objective: The aim of this study was to investigate the role of the clinical course and prognosis of serum levels of beta-defensin-2 [BD-2] in patients with Crimean-Congo hemorrhagic fever [CCHF]

Subjects and Methods: Patients who were hospitalized in the Department of Infectious Diseases and Clinical Microbiology of the Faculty of Medicine, Ataturk University, were considered for inclusion in this study. The patients had positive real-time reverse transcription polymerase chain reaction and/or enzyme-linked immunosorbent assay results of the CCHF virus. There were 60 patients with CCHF in the study group and 25 healthy participants in the control group. Serum BD-2 levels were measured using ELISA. Data were analyzed using the Student t test or Mann- Whitney U test

Results:Of the 60 patients, 6 [10%] died and 54 [90%] were discharged following their recovery. The mean BD-2 level of the patient group was significantly higher [4,180.30 +/- 3,944.19 pg/ml] than that of the control group [964.45 +/- 266.07 pg/ml; p = 0.001]. Serum BD-2 levels of the patients with fatal [1,529.81 +/- 1,028.14] and nonfatal disease [4,474.80 +/- 4,041.58] differed, but this difference showed only borderline significance [p = 0.055]. The mean BD-2 level of the severe group was 5,507.45 +/- 4,327.06 pg/ml, while it was 3,611.52 +/- 3,676.73 pg/ml in the mild/moderate group, and both were significantly higher than that of the control group [p = 0.001]

Conclusion:In this study, the expression of serum BD-2 was raised in patients with CCHF, and this increase may beneficially affect survival. Studies with larger sample sizes are needed to confirm the association of serum BD-2 with CCHF prognosis

The association between serum YKL-40 levels, mean platelet volume, and c-reactive protein in patients with cellulitis.

Background: Lower limb cellulitis is an infectious disease that has serious complications unless it is treated. Objectives: In this pilot study, we evaluated whether levels of YKL-40, an acute-phase reactant, and mean platelet volume (MPV), which occurs secondary to infl ammation in cellulitis, increase compared to healthy subjects. We also aimed to investigate the association between YKL-40 and MPV in the prognosis of the patients. Material and Methods: A total of 55 patients with cellulitis (23 men and 32 women) and a similar age group of 46 healthy individuals (22 men and 24 women) were included in the study. Cellulitis was diagnosed according to guideline. Serum YKL-40 levels, MPV, C-reactive protein (CRP), and other biochemical values of both groups were compared. Results: YKL-40 levels (52.2 ± 34.5 ng/mL vs 34.6 ± 18.0 ng/mL, P = 0.004), MPV (7.7 ± 1.0 fL vs 6.9 ± 0.7 fL, P < 0.001), and CRP (9.5 ± 8.2 mg/dL vs 0.7 ± 0.6 mg/dL, P < 0.001) were signifi cantly higher in the patients with cellulitis than the control. The mean recovery time (RT) of the patients was 22.6 ± 6.9 days. We found that YKL-40 (odds ratio [OR] 0.1, confi dence interval [Cl] 0.028–0.191, P = 0.009) and MPV (OR 2.4, Cl 0.254-4.578, P = 0.029) have an independent association with RT. Conclusion: YKL-40 and MPV values were correlated with higher CRP in the cellulitis group than in controls. According to these results, increased YKL-40 and MPV levels might be a prognostic factor for cellulitis in patients.

Comparison of Lichtenstein and darn repair techniques in terms of recurrence

Between the years 2004 and 2008, the file records of 121 patients with inguinal hernia, who were operated on by the same surgeon with Lichtenstein and darn repair techniques in three state hospitals, were retrospectively compared in terms of relapse. Of these, 61 patients were operated with the darn repair technique, while 60 patients underwent hernia repair with the Lichtenstein technique. When the patients were evaluated in terms of postoperative recurrence, no difference was found between two groups. Also, the darn repair technique was considered more economical as no meshes were used

Analysis of clinical, pathological, and treatment factors in gastric cancer

A retrospective study of 122 patients, who were operated between January 1989 and December 2001, was performed D1 dissection was performed in the operations. In this study, initiatives that do not leave macroscopic tumor behind were evaluated as curative resections. The patients who underwent total gastrectomy were mostly reconstructed with omega loop and Braun anastomosis. Among the patients, 81 [66.4%] were male and 41 [33.6%] female. The youngest patient was 26 and the oldest 82 years old. The average age of patients was 58.9 years. Fifty seven patients [46.7%] were treated with curative [R1] resection, while 20 [16.4%] with palliative resection, 20 [16.4%] with surgical bypass, 5 [4.2%] with gastrostomy, 2 [1.6%] with nutritional jejunostomy, and 18 [14.7%] underwent only explorative laparotomy. Patients who were operated were identified as follows: 3 of the patients [2.4%] were in Stage IA, 4 [3.2%] in Stage IB, 23 [18.8%] in Stage II, 11 [9.1%] in Stage IIIA, 16 [13.2%] in Stage IIIB, and 55 [53.3%] in Stage IV. The average life expectancy in the survival analysis of all patients was 44 [ +/- 3] months and the 5-year survival rate was 42.5%. Survival results were found to be consistent with western-sourced results. These results have led to the need of comparison of D1 and D2 dissections with a prospective randomized study

Serum Pentraxin-3 level in patients who underwent coronary angiography and relationship with coronary athersclerosis

Objectives: To evaluate the role of pentraxin-3 [PTX-3] in determining the presence and severity of coronary atherosclerosis in patients with coronary artery disease [CAD]

Subjects and Methods: Ninety-five patients [77 males and 18 females] who underwent elective coronary angiography were enrolled in this study. Patients with heart failure, renal failure, diabetes and thyroid disease were excluded. The study population was divided into 3 groups: individuals with normal coronary arteries, patients with critical CAD [n = 35] and patients with noncritical CAD [n = 36]. The association of PTX-3 levels with the presence and severity of CAD and the number of involved vessels were analyzed

Results: The mean age was 53.40 +/- 10.25 years. The PTX-3 levels were significantly higher in patients with CAD than without CAD [146.48 +/- 48.52 vs. 109.83 +/- 49.06 pg/ml, p < 0.001]. A statistically significant difference was found among the 3 groups regarding the severity of CAD [165.66 +/- 49.10, 127.83 +/- 40.51 and 109.83 +/- 49.06 pg/ml, p < 0.001, respectively]. The serum PTX-3 levels in normal arteries were 110.4 +/- 48.11 pg/ml, in single-vessel disease 132.35 +/- 32.96 pg/ml, in 2-vessel disease 142.57 +/- 55.88 pg/ml, in 3-vessel disease 156.07 +/- 50.53 pg/ml, and in 3-vessel disease 160.50 +/- 30.41 pg/ml. After adjusting for baseline confounders, older age [OR = 1.107, 95% CI = 1.027-1.193, p = 0.008] and higher PTX-3 levels [OR = 1.017, 95% CI = 1.003-1.032, p = 0.021] were detected as significant predictors for the presence of CAD

Conclusions: Higher PTX-3 levels were associated with the presence of CAD and its increased severity in clinically stable patients. Higher PTX-3 levels may be regarded as a novel diagnostic predictor and may offer therapeutic options in the clinic

Serum Fibronectin Levels in Acute and Chronic Viral Hepatitis Patients

Background: The aim of this study was to investigate the serum fibronectin (FN) levels and liver enzyme activities in patients with acute hepatitis (A, B, C) and chronic viral hepatitis (B, C); determine whether the virus types correlated with disease severity; and assess whether FN could be used as a marker of virus type or disease severity in patients. Methods: A total of 60 subjects were enrolled in the study, including 20 patients with acute hepatitis (A, B, C), 20 with chronic hepatitis (B, C), and 20 healthy controls. Serum fibronectin (FN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and albumin were measured in all patients from blood samples. Results: Serum FN levels were significantly lower in acute (122.9 μg/mL (SD 43.1), P < 0.001) and chronic hepatitis patients (135.7 μg/mL (SD 46.0), P < 0 .001) compared to controls 221.4 μg/mL (SD 32.5). A negative correlation was found between serum FN and AST (r2 = 0.528, P < 0.001), ALT (r2 = 0.425, P < 0.001), and GGT (r2 = 0.339, P < 0.001). Additionally, high serum GGT levels (β = –0.375, P = 0.010), and low serum albumin levels (β = –0.305, P = 0.008) were associated with low serum FN levels. Conclusion: Serum FN levels were lower in both acute and chronic hepatitis patients, and an inverse relationship between serum FN and serum AST, ALT, and GGT levels was found. A decrease in serum FN levels may indicate hepatitis severity as AST and ALT represent hepatocyte damage.

An interesting ileus case: Morgagni hernia

Morgagni hernia is a congenital defect that occurs in adult patients without the presence of a traumatic event. In this case a 76 years old male patient is described who admitted to emergency room with abdominal pain and obstipation. The diaghragma defect was repaired and the herniated sac was reducted in the emergent laparotomy applied

The expressions of HSP70 and alphaB-crystallin in myocarditis associated with foot-and-mouth disease virus in lambs

This study describes the expression of heat shock protein70 (HSP70) and alpha-basic-crystallin (alpha-BC) and their association with apoptosis and some related adaptor proteins in the pathogenesis of foot-and-mouth disease virus (FMDV)-induced myocarditis in lambs. HSP70 was generally overexpressed in the myocardial tissues and inflammatory cells of FMDV-induced myocarditis with differential accumulation and localization in same hearts when compared to non-foot-and-mouth disease control hearts. alpha-BC immunolabeling showed coarse aggregations in the Z line of the cardiomyocytes in FMDV-infected hearts in contrast to control hearts. Overall, the results of this study show that the anti-apoptotic proteins, HSP70 and alpha-BC, were overexpressed with increased apoptosis in FMDV-infected heart tissues. Both proteins failed to protect the cardiomyocytes from apoptosis as defense mechanisms to the FMDV during the infection, suggesting that the virus is able to increase apoptosis via both downregulation and/or upregulation of these anti-apoptotic proteins.